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Abstract supplement
XIX International AIDS Conference
22 – 27 July 2012, Washington DC, USA
Volume 15, Supplement 3
October 2012
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Abstract supplement
XIX International AIDS Conference
22 – 27 July 2012
Contents
Track A: Basic Science
Track B: Clinical Science
Track C: Epidemiology and Prevention Science
Track D: Social Science, Human Rights and Political Science
Track E: Implementation Science, Health Systems and Economics
1
33
76
162
236
Author Index
288
Volume 15, Supplement 3
October 2012
http://www.jiasociety.org/index.php/jias/issue/view/1460
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
http://www.jiasociety.org/index.php/jias/article/view/18438 | http://dx.doi.org/10.7448/IAS.15.5.18438
Track A Basic Science
A4 - Bioinformatic analysis of viral diversity
in natural
THPDA0203
HIVToolbox: an integrated web application for investigating
HIV
D. Sargeant1, S. Deverasetty2, Y. Luo3, A. Villahoz-Baleta4, S. Zobrist1,
V. Rathnayake1, J. Russo1, M. Muesing3 and M. Schiller1
1
University of Nevada Las Vegas, School of Life Sciences, Las Vegas,
United States. 2University of California Los Angeles, Medical Center,
Los Angeles, United States. 3Aaron Diamond AIDS Research Center,
New York, United States. 4University of Massachusetts, Boston,
United States
Presenting author email: david.sargeant@unlv.edu
Background: Many HIV databases and applications focus on a limited
domain of HIV knowledge. Since even a ‘‘simple’’ organism like HIV
represents a very complex system with many interacting elements,
Figure 1.
the fractured structure of existing databases and applications likely
limits our ability to investigate and understand HIV. To facilitate
research, therefore, we have built HIVToolbox, which integrates
much of the knowledge about HIV proteins and presents the data in
an interactive web application. HIVToolbox allows quick and
convenient hypotheses generation, experiment interpretation, and
potential new drug structure creation.
Methods: HIVToolbox was built as a standard three-tier J2EE web
application, consisting of 1) an underlying relational MySQL database,
2) a set of standard Java data access objects that pull data from the
database, and 3) a set of dynamic web pages the user interacts with.
HIV-1 data from external sources such as the Protein Data Bank, NCBI,
Los Alamos, etc. was collected, curated, and stored in the HIVToolbox
database. Additional data, such as homology and position statistics
matrices, was generated from existing data. Since version 1, drug
binding site and drug resistant mutation data has also been added.
Results: HIVToolbox was used to create several new hypotheses
about HIV-1 integrase, including predicting the location of a CK2
phosphorylation site, which was later confirmed by experiment.
Protease with drug Amprenavir shown [Interactive HIV protein page].
1
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
A new version of HIVToolbox support display of the 3D locations
of drug resistant mutations on surface plots of HIV proteins and
the drug binding sites for structures of complexes of HIV proteins
with drugs.
Conclusion: HIVToolbox is an open-access web application that
allows virologists and structural biologists to access detailed
information about HIV-1 proteins, such as sequence, structure,
functional sites and relationships, homology, drug binding sites,
and drug resistant mutations, and to immediately see the relationships between any or all of them. Weblink: [http://hivtoolbox.biotoolkit.com]
A7 - Virus-specific humoral immunity
WEAA0103
Production and characterization of human anti-V3
monoclonal antibodies from Indian clade C human
immunodeficiency virus type-1 (HIV-1) infected patients
R. Andrabi1, R. Kumar1, M. Bala2, A. Nair1, A. Biswas3, N. Wig3,
P. Kumar4 and K. Luthra1
1
All India Institute of Medical Sciences, Biochemistry, New Delhi,
India. 2Regional STD Teaching Training & Research Centre, Safdarjang
Hospital, New Delhi, India. 3All India Institute of Medical Sciences,
Medicine, New Delhi, India. 4All India Institute of Medical Sciences,
Medical Physics Unit, New Delhi, India
Presenting author email: raieesandrabi@gmail.com
Background: Analysis of human monoclonal antibodies (mAbs)
developed from HIV-1 infected donors have enormously contributed
to the identification of neutralization sensitive epitopes on the HIV-1
envelope glycoprotein. The third variable region (V3) is a crucial
target on gp120, primarily due to its involvement in co-receptor
(CXCR4 or CCR5) binding and presence of epitopes recognized by
broadly neutralizing antibodies.
Methods: Thirty-three HIV-1 seropositive drug naive patients (18
males and 15 females) within the age range of 20-57 years
(median 33 years) were recruited in this study for mAb production.
The mAbs were selected from EBV transformed cultures with
conformationally constrained Cholera-toxin-B containing V3C (V3CCTB) fusion protein. We tested the mAbs for their binding with HIV-1
derived proteins and peptides by ELISA and for neutralization against
HIV-1 viruses by TZM-bl assays.
Results: We isolated three anti-V3 mAbs, 277, 903 and 904 from the
cells of different individuals. The ELISA binding revealed a subtype-C
and subtype-A specific binding of antibody 277 and 903 while 904
exhibited cross reactivity also with subtype-B V3. Epitope mapping of
mAbs with overlapping V3 peptides showed exclusive binding to V3
crown. The antibodies displayed high and low neutralizing activity
against 2/5 tier 1 and 1/6 tier 2 viruses respectively. Overall, we
observed a resistance of the tier 2 viruses to neutralization by the antiV3 mAbs, despite exposure of the epitopes recognized by these
antibodies on the native viruses, as determined by intact virion binding
assay with two representative subtype-C and B viruses (Du156.12 and
JRFL).
Conclusion: Our study suggests that the anti-V3 antibodies derived
from subtype-C infected Indian patients display neutralization
potential against tier 1 viruses. Defining the epitope specificities of
these mAbs and further experimental manipulations will be helpful
in identification of epitopes, unique to clade C or shared with nonclade C viruses, for immunogen design.
Track A Basic Science
TUPDA0104
Characterization of broadly neutralizing antibodies (bNAbs)
to HIV-1 present in a cohort of long term non-progressors
(LTNPs)
N. Gonzalez1, K. McKee2, E. Yuste3, J.R. Mascola2 and J. Alcamı́1
1
Instituto de Salud Carlos III, AIDS Immunopathogenesis Unit,
Madrid, Spain. 2Vaccine Research Center, NIH, Bethesda
United States. 3Hospital Clinic, Barcelona, Spain
Presenting author email: nglez@isciii.es
Background: One major obstacle to induce bNAbs resides in the high
variability of the viral envelope and structural mechanisms hiding
crucial epitopes. Besides, maturation of bNAbs against HIV represents
a difficult process that can be impaired by the immunodeficiency
associated with HIV infection. We have explored the hypothesis that
preserved B cell function in LTNPs could result in the production of
bNAbs at higher frequency and increased affinity in comparison with
HIV progressors.
Methods: Samples (142) from the cohort of LTNPs (median RNA
copies/ml: 87, median CD4: 802 cells/ml) were kindly provided by
the HIV BioBank integrated in the Spanish AIDS Research Network
(RIS). A control population of 191 untreated patients (median RNA
copies/ml: 10,241, median CD4: 567 cells/ml) from Hospital Clinic,
Barcelona, was analyzed. Sera at 1/200 and 1/2000 dilutions were
preincubated with Env recombinant viruses harboring a luciferase
gene and then added to U87.CD4.CXCR4/CCR5. bNAbs specificities
were studied by ELISA using mutated gp120 that abrogates antibody
binding, competition ELISA with biotinylated antibodies, neutralization assays with mutated viruses and peptide competition neutralization assays.
Results: The percentage of elite neutralizers was higher in the LTNPs
(9.3%) than in the control population (3.7%). Broadly neutralizing sera
were screened for the presence of epitope-specific antibodies. CD4
binding site antibodies were detected in several sera. To determine
whether these antibodies were responsible for broad neutralization,
competition neutralization assays using RSC3 (antigenically resurfaced glycoprotein containing the CD4bs) were performed. RSC3
addition inhibited neutralization mediated by 16.7% of sera in LTNPs
and 12.5% sera of the control population. Anti-MPER antibodies were
detected in 50% individuals of both populations, including several
sera with 4E10-like antibodies. Glycan-dependent HIV-1 NAbs were
more abundant in LTNPs (66%) than in control population (37%).
Conclusion: Broad humoral immune responses against HIV-1 were
more common among LTNP than a control population of untreated
HIV-1-infected donors.
A8 - Virus-specific cellular immunity
MOAA0202
The majority of freshly sorted SIV-specific CD8 T cells
cannot suppress viral replication in SIV-infected macrophages
L. Vojnov1, M. Martins1, A. Bean1, M. Veloso de Santana2, J. Sacha3,
N. Wilson1, M. Bonaldo4, R. Galler4, M. Stevenson5 and D. Watkins5
1
University of Wisconsin-Madison, Madison, United States. 2Instituto
Oswaldo Cruz-FIOCRUZ, Rio de Janeiro, Brazil. 3Oregon Health and
Science University, Beaverton, United States. 4Fundação Oswaldo
Cruz, Rio de Janeiro, Brazil. 5University of Miami Miller School of
Medicine, Miami, United States
Presenting author email: laravojnov@gmail.com
2
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Background: HIV/SIV primarily infect activated CD4 T cells, but
can infect macrophages. Because of the relatively small percentage of
infected macrophages, the interaction between antigen-specific CD8
T cells and infected macrophages in HIV/SIV infection has been poorly
studied. We, therefore, sought to determine whether SIV-specific
CD8 T cells could control viral replication in infected macrophages.
Methods: We wanted to ascertain whether ex vivo tetramersorted SIV-specific CD8 T cells could suppress viral replication in
SIVmac239/316e- and SIVsmE660-infected macrophages using a
recently developed 48-hour viral suppression assay. We reasoned
that freshly sorted CD8 T cells might be more representative of
the in vivo properties of CD8 T cells than in vitro cultured cell lines
and clones.
Results: Surprisingly, both ex vivo tetramer-sorted SIV-specific CD8
T cells and bulk CD8 T cells that eliminated and suppressed viral
replication in SIV-infected CD4 T cells were inefficient at controlling
viral replication in SIV-infected macrophages. Our data suggest that
macrophages may be an important reservoir for SIV because it may
be difficult for SIV-specific CD8 T cells to suppress viral replication
in this particular cell type.
Conclusion: It is possible, therefore, that while AIDS virus-infected
macrophages only constitute a small percentage of all virus-infected
cells, they may be relatively resistant to CD8 T cell-mediated lysis
and continue to produce virus over long periods of time. Thus,
macrophages could actually be contributing significantly to viral
Track A Basic Science
production. Induction of HIV/SIV-specific CD8 T cells capable of
killing infected macrophages or preventing establishment of the
macrophage reservoir HIV might be critical for controlling viral
replication.
MOLBA04
Comparative activity of IgA mediated antibody dependent
cell-mediated cytotoxicity (ADCC) in the genital mucosa of
HIV seroconverters and highly exposed seronegative
women
M. Aziz1,2, M. Mata1, F. Mahmood1, H. Durkin3, C. Liu4,
R. Greenblatt5, M. Nowicki6, E. Golub7, K. Anastos8, A. French1,2 and
L. Baum1
1
Rush University Medical Center, Chicago, United States. 2Cook
County Health & Hospital Systems, Chicago, United States. 3SUNY
Downstate Medical Center, Brooklyn, United States. 4Georgetown
University, Washington, United States. 5University of California, San
Francisco, United States. 6University of Southern California Norris
Hospital, Los Angeles, United States. 7Johns Hopkins University,
Baltimore, United States. 8Montefiore Medical Center, Section of
Infectious Diseases, Bronx, United States
Presenting author email: mariam_aziz@rush.edu
Figure 1.
3
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track A Basic Science
highly exposed seronegative women who had unprotected sex with
known positive partners.
Methods: A 51Cr-release assay with natural killer cells or monocytes
as effectors was used to measure IgG or IgA mediated ADCC against
clade specific gp120 coupled target cells. We analyzed CVL from ESN
at one visit, and SC at intervals from one yr pre-seroconversion (PSC)
to 6.5 yr after seroconversion (ASC). We evaluated activity at 4, 10
fold serial dilutions starting with a 1/10 dilution.
Results: Figure 1 (top)shows shows minimal to no activity of IgG
mediated ADCC in the CVL of 10 ESN. Figure 1(bottom) shows IgA
mediated ADCC in the CVL of the same 10 ESN. 4 patients show
significant activity above background activity. At the peak dilution,
patient 4 shows 27.3% Specific Release (SR), patient 6 shows 14.5
%SR, patient 8 shows 17.9 %SR and patient 10 shows 17.6 %SR.
Figure 2 and 3 shows no IgA mediated ADCC activity in CVL of 2
seroconverters from PSC to 6.5 years ASC even while IgG activity is
present in later visits.
Conclusion: HIV IgA in CVL samples was associated with ADCC and
lack of HIV infection in exposed women, indicating that genital HIV IgA
may contribute to protection from infection. Further studies need to
be done to determine if IgA mediated ADCC antibodies may be
protective in ESN.
TUPDA0101
Figure 2.
The colocalization potential of HIV-specific CD8 and
CD4 T cells is mediated by integrin b7 but not CCR6 and
regulated by retinoic acid
V.S. Wacleche1,2, N. Chomont3, A. Gosselin2, P. Monteiro1,2,4,
M. Goupil1, H. Kared1,2, C. Tremblay1,2, N. Bernard5, M.-R. Boulassel6,
J.-P. Routy4,6,7 and P. Ancuta1,2,4
1
Université de Montréal, Microbiology and Immunology, Montreal,
Canada. 2Centre Hospitalier de l’Université de Montréal- Research
Centre, Montreal, Canada. 3VGTI-Florida, Port St Lucie, United States.
4
INSERM Unit 743, Montreal, Canada. 5Research Institute of the
McGill University Health Centre, Montreal, Canada. 6Division of
Hematology, McGill University Health Centre, Montreal, Canada.
7
Immunodeficiency Service, Montreal Chest Institute, McGill
University Health Centre, Montreal, Canada
Presenting author email: vanessa.sue.wacleche@umontreal.ca
Figure 3.
Background: The potential role of ADCC in prevention of infection is
suggested by the RV144 HIV vaccine trial where non-neutralizing
antibodies contributed to protection against infection with HIV.
Studies from Kenya showed that HIV specific IgA in cervical fluid
was present in uninfected sex workers. We aimed to analyze
cervicovaginal lavage fluid(CVL) from 2 seroconverters (SC) and 10
Background: CD4 T-cells from gut-associated lymphoid tissues
(GALT) are major HIV-1 targets. Recruitment of excess effector CD8
T-cells in the proximity of target cells is critical for the control of viral
replication. We investigated the colocalization potential of HIVspecific CD8 and CD4 T-cells into the GALT and explored the role
of retinoic acid (RA) in regulating this process in a cohort of HIVinfected subjects with slow disease progression (SP).
Methods: Five SP subjects were available for this study: median CD4
counts 670 cells/ml, plasma viral load 3.27 log10 HIV-RNA copies/ml,
and 15 years of infection. PBMC were exposed to HIV peptides or
CMVpp-65 protein in the presence or absence of all-trans RA (ATRA)
or the RA antagonist LE540. The expression of trafficking molecules
on antigen specific T-cells was analyzed by flow cytometry using the
CFSE assay.
Results: The expression of the gut-homing molecules integrin b7,
CCR6, and CXCR3 was identified as a ‘‘signature’’ for HIV-specific but
not CMV-specific CD4 T-cells, thus providing a new explanation for
their enhanced permissiveness to infection in vivo. HIV-specific CD8
T-cells expressed high levels of integrin b7 and CXCR3; however CCR6
was detected at superior levels on HIV-specific CD4 versus CD8 Tcells. ATRA upregulated the expression of integrin b7 but not CCR6
on HIV-specific T-cells.
Conclusion: HIV-specific CD8 T-cells may colocalize in excess with
CD4 T-cells into the GALT via integrin b7 and CXCR3, but not CCR6.
4
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track A Basic Science
Considering our previous findings that CCR6CD4 T-cells are
major HIV targets, a limited ability of CD8 T-cells to migrate in
the vicinity of CCR6CD4 T-cells may facilitate HIV dissemination at
mucosal sites. In addition to other previously described T-cell
features (e.g., antiviral properties, poly-functionality, and exhaustion), the colocalization potential of CD4 and CD8 T-cells
represents a new parameter to consider for predicting the efficacy
of anti-HIV responses.
Institut Pasteur, Unité d’Immunogénétique Cellulaire, Paris, France.
INSERM U802, Bicêtre Hospital, Le Kremlin-Bicêtre, France. 3AP-HP,
Department of Infectious and Tropical Diseases, Raymond Poincaré
Hospital, Garches, France. 4AP-HP, Department of Infectious and
Tropical Diseases, Tenon Hospital, Paris, France. 5INSERM U822,
Bicêtre Hospital, Le Kremlin-Bicêtre, France. 6Benaroya Research
Institute at Virginia Mason, Seattle, United States. 7Unité de
Dynamiques des Réponses Immunes and INSERM U668, Institut
Pasteur, Paris, France
Presenting author email: chakra@pasteur.fr
TUPDA0105
Background: HIV Controllers are rare individuals who spontaneously
control HIV replication in the absence of antiretroviral therapy.
To identify parameters of the CD4 response that may contribute to
viral control, rather than merely reflect a persistently low viremia,
we compared the T helper profile in two groups of patients with
more than 10 years of viral suppression: HIV Controllers from the
ANRS CO18 cohort (n 26) and efficiently treated patients (n 16).
Methods: Cells specific for immunodominant Gag and CMV peptides
were evaluated for the production of 10 cytokines and cytotoxicity
markers, and were also directly quantified ex vivo by MHC class II
tetramer staining.
Results: HIV Controller CD4 T cells were characterized by a higher
frequency of IFN-g production, perforin/CD107a expression, and
polyfunctionality in response to Gag peptides. While IL-4, IL-17, and
IL-21 production did not differ between groups, treated patients cells
produced more IL-10 in response to Gag and CMV peptides, pointing
to persistent negative immunoregulation after long-term antiretroviral therapy. Gag293 tetramer-positive cells were detected at high
frequency (0.15%) and correlated positively with IFN-g producing
CD4 T cells in the Controller group (R 0.84; P 0.01). Tetramerpositive cells were fewer in the HAART group (0.04%) and did not
correlate with IFN-g production, supporting the notion of a
persistent immune dysfunction in HIV-specific CD4 T cells of
treated patients.
Conclusion: HIV Controllers maintained a population of highly
efficient Th1 effectors directed against Gag in spite of a persistently
low antigenemia, while patients treated in the long-term showed a
loss of CD4 effector functions.
We previously reported that HIV Controllers harbored a unique population of CD4 T cells expressing high avidity TCRs directed against
Gag293. We propose that high avidity drives continuous Th1 effector
differentiation in response to low antigen concentrations and explains
the persistence of an activated antiviral response in HIV Controllers.
Enhanced TCR affinity imparts specificity to reverse
transcriptase inhibitor resistance-associated mutations
J. Jadlowsky1, C. Baiduc1, M. Richardson1, A. Bennett2, B. Jakobsen2
and J.L. Riley1
1
University of Pennsylvania, Philadelphia, United States.
2
Adaptimmune, Abingdon, United Kingdom
Presenting author email: juliejad@mail.med.upenn.edu
Background: An attractive approach for restoring CTL activity to HIV1 infected individuals is the adoptive transfer of autologous CD8 T
cells that have been transduced with an HIV-1 specific TCR.
Previously, we described an HLA-A2-SL9 specific TCR that when
introduced into CD8 T cells could control HIV-1 replication in an in
vitro suppression assay. Given that the success of HAART is based, in
part, on attacking multiple targets, we isolated an additional HLA-A2
restricted, HIV-1 specific TCR targeting the HIV-1POL sequence
YQYMDDLYV. This epitope is of great clinical relevance because it
lies within the active site of Pol and is a target of many reverse
transcriptase inhibitors.
Methods: By surface plasmon resonance, we defined the Kd of this
wild type TCR to be 6.7mM and t1/2 to be 2.7s. Using phage display, a
panel of affinity enhanced A2-YV9 TCRs were obtained with Kd values
ranging from 5.1 to 0.3mM.
Results: When introduced into CD8 T cells by lentiviral vectors,
the A2 YV9 specific TCRs were highly specific for the wild type
epitope. In contrast to what we previously determined for CD8 T cells
transduced with the wild type A2-SL9 specific TCR, we observed that
the A2-YV9 specific T cells could respond in a polyfunctional manner
by simultaneously producing TNF-a, IFN-g, IL-2, and MIP1-b when
presented with a wide range of peptide concentrations. Moreover,
affinity enhanced A2-YV9 specific CD8 T cells were able to recognize
and respond to several variants of the wild type sequence, including
those responsible for resistance to NNRTI and NRTI such as
Nevirapine, Didanosine and Efavirenz.
Conclusion: Together, our data suggest that adoptive transfer of
these A2-YV9 specific CD8 T cells presents great potential for
augmenting available treatments and imparting additional control
to HIV-1 infected individuals experiencing drug resistance.
A9 - Immune responses in resistant
cohorts: elite controlers and exposed
uninfected
MOAA0201
HIV controllers maintain a population of highly efficient Th1
effector cells in spite of persistently low viral antigenemia
B. Vingert1, D. Benati1, O. Lambotte2, P. de Truchis3, L. Slama4,
P. Jeannin1, S. Perez-Patrigeon1, F. Boufassa5, W.W. Kwok6,
F. Lemaı̂tre7, J.-F. Delfraissy2, J. Thèze1 and L.A. Chakrabarti1
1
2
MOAA0204
Natural control of HIV infection is associated with an
isotype switched IgG antibody response to HIV core
antigens in patients with ‘non-protective’ HLA-B alleles
M. French1, R. Center2, K. Wilson3, I. Fleyfel1, S. Fernandez1 and
A. Kelleher4
1
University of Western Australia, School of Pathology and Laboratory
Medicine, Perth, Australia. 2University of Melbourne, Microbiology
and Immunology, Melbourne, Australia. 3National Serology
Reference Laboratory, Melbourne, Australia. 4University of New
South Wales, Kirby Institute, Sydney, Australia
Presenting author email: martyn.french@uwa.gov.au
Background: Natural control of HIV infection is associated with CD8 T
cell responses to HIV core antigens, encoded by Gag, restricted by
‘protective’ HLA-B alleles (HLA-B27, -57, -58). Slower progression of
HIV infection is associated with antibodies to HIV core proteins but mechanisms are unclear. Antibody responses that have isotype switched
to IgG2 may be particularly effective. We have investigated this further.
5
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Methods: Plasma from 32 HIV controllers (HIV RNA B2000 copies/
mL, including 14 elite controllers) and 21 ART-naive non-controllers
(CD4 T cell count B100/uL) were assayed for IgG1 and IgG2
antibodies to non-recombinant HIV proteins by western blot (WB)
assay and to recombinant (r) p55 (Gag) and gp140 (Env) by ELISA.
A positive antibody response was defined as a WB band score of 4 or
an ELISA optical density 2SD of non-HIV sera for rp55 antibodies.
Antibodies to rgp140 were titred. Controllers were HLA typed by
sequenced-based typing using genomic DNA.
Results: Controllers had a positive IgG1 or IgG2 antibody response to
one or more core protein (p17, p24) on WB more often than noncontrollers (75% vs 28.6%, p0.0016 and 22% vs 0, p0.034,
respectively). Also, 12.5% of controllers but no non-controllers had a
positive IgG2 antibody to rp55 (p 0.14). When results of WB assays
and ELISA were combined, 34% of controllers but no non-controllers
had positive IgG2 antibodies to core antigens (p 0.04). Positive
IgG2 antibodies to core antigens were more common in patients
without ‘protective’ HLA-B alleles (57%) than patients with these
alleles (16.5%) (p 0.026). Positive IgG1 antibodies to Pol-encoded
proteins were also more common in controllers (p 0.0003) but
IgG2 antibodies were not detected. IgG1 and IgG2 antibodies to
envelope antigens showed few differences.
Conclusion: An isotype switched IgG antibody response to HIV core
antigens is associated with control of HIV infection in patients
without ‘protective’ HLA-B alleles.
MOPDA0104
ZNDR1 gene affects host susceptibility to HIV-1 infection
P. An1, J. Goedert2, S. Donfield3, S. Buchbinder4, G. Kirk5, R. Detels6
and C. Winkler1
1
SAIC-Frederick, Inc., NCI Frederick, Frederick, United States.
2
National Cancer Institute, Infections and Immunoepidemology
Branch, Division of Cancer Epidemiology and Genetics, Bethesda,
United States. 3Rho Inc, Chapel Hill, United States. 4San Francisco
Department of Public Health, San Francisco, United States. 5Johns
Hopkins University School of Public Health, Baltimore, United States.
6
School of Public Health, University of California, Los Angeles,
United States
Presenting author email: anp@mail.nih.gov
Background: A recent genome-wide association study (GWAS) of
host determinants for HIV-1 disease revealed that single nucleotide
polymorphisms (SNPs) near genes HLA-C and ZNRD1 were associated
with setpoint HIV-1 viral load and disease progression. ZNRD1 has
also been identified as a host protein required by HIV-1 life cycle in a
genome-wide functional genomic study.
Methods: We investigated the effects of 13 SNPs in the ZNRD1
region on HIV-1 infection and progression in five U.S-based
treatment-naive HIV-1 longitudinal cohorts consisting of homosexuals, hemophiliacs and injection drug users (IDUs) (n 1028). Allelic
frequencies were compared between HIV-1 seronegatives (SN) and
seroconverters (SC) with further analysis focusing on high-risk
exposed HIV-1-uninfected individuals (HREU) compared to HIV-1
seroconverters (SC). Among HIV- 1 seroconverters, variation in time
to clinical AIDS was assessed by haplotype. Electrophoretic mobility
shift assay (EMSA) was used to assess the associated SNP’s potential
to alter DNA-protein interactions.
Results: A haplotype in the ZNRD1 gene showed significant
association with decreased risk of HIV-1 acquisition (OR 0.65,
95% CI 0.47-0.89), independent of the effect of HLA-C rs9264942. The
tag SNP allele in the ZNRD1 promoter region causes a loss of nuclear
factor binding, as revealed by EMSA. This differential binding was
further shown to be cell-specific, occurring in Hela epithelial cells
Track A Basic Science
instead of Jurkat T-cells (stimulated or unstimulated), suggesting its
regulatory role in mucosal epithelial barriers influence HIV-1
transmission. Indeed, this infection effect was not observed in HIV1 infected IDUs (OR 0.82, 95% CI, 0.44-1.54). On the other hand,
SNPs and haplotypes for ZNRD1 modestly affect progression rate to
AIDS.
Conclusion: This study provided novel evidence supporting a
direct role of ZRND1 in modulating HIV and identified a ZNRD1
allele as a host resistant factor to HIV-1 acquisition. (Funded by NCI
HHSN26120080001E)
TUPDB0201
Evidence for T cell immune quiescence in the genital
mucosa of HIV exposed seronegative commercial sex
workers
J. Lajoie1, J. Juno1, A. Burgener1, S. Rahman2, K. Mogk2, C. Wachihi3,
J. Mwanjewe1,3, F.A. Plummer1,4, J. Kimani1,3, T.B. Ball2,4,5 and
K.R. Fowke1,5
1
University of Manitoba, Winnipeg, Canada. 2University of Manitoba,
Medical Microbiology, Winnipeg, Canada. 3Kenya AIDS Contol
Program, Nairobi, Kenya. 4Public Health Agency of Canada, Winnipeg,
Canada. 5University of Nairobi, Nairobi, Kenya
Presenting author email: julie.lajoie1@gmail.com
Background: Understanding the early events during heterosexual HIV
transmission at the genital mucosa is necessary to develop a safe and
efficacious HIV microbicide or vaccine. A recent workshop highlighted the benefits of studying Highly Exposed Seronegative (HESN)
individuals in order to identify and describe correlates of HIV
protection. In an HESN cohort of commercial sex workers in Nairobi,
Kenya, we have described a state of reduced systemic T cell immune
activatio termed Immune Quiescence. However, the extent of
Immune Quiescence at the genital mucosal is not known. This study
characterized the female genital mucosal profile of cells, cytokines
and chemokines involved in immune activation and lymphocyte
recruitment among HESN.
Methods: CVL and plasma from commercial sex workers from the
Majengo clinic in Nairobi, Kenya (57 HIV- followed for B3 years; 68 HIV
infected and 55 HESN followed for 7 years) were analysed for the
presence of 22 cytokines/chemokines and five antiproteases previously associated with resistance to HIV infection. Activation of
cervico vaginal cells was analysed by multiparametric flow cytometry.
Results: HESN women have a unique pattern of mucosal chemokine/
cytokine expression. HESN subjects showed lower expression of MIG,
IP-10 and IL-1a as well as higher levels of antiproteases. Among the
HESN women there was a distinct chemokine gradient between the
blood and genital mucosa relative to control women.
Conclusion: MIG and IP-10 are important regulators of T cell
trafficking to the genital mucosa while IL-1a is an indicator of
immune activation. The reduced levels of these cytokines/chemokines together with the unique correlations observed with antiprotease expression among HESN women suggest that the Immune
Quiescent phenotype extends to the female genital tract. Reducing
the number of activated CD4 T cells in the FGT could limit cellular
targets for HIV infection and may be an important component to
resisting HIV infection.
WEPDA0105
Highly HIV exposed seronegative (HESN) sex workers from
Nairobi, Kenya have altered innate mucosal immune
responses at the level of the female genital tract
6
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
A. Burgener1, J. Lajoie1, C. Wachihi2, J. Kimani1,2, K. Fowke1,2,
F.A. Plummer1,3 and T.B. Ball1,2,4
1
University of Manitoba, Winnipeg, Canada. 2University of Nairobi,
Nairobi, Kenya. 3Public Health Agency of Canada, Winnipeg, Canada.
4
Public Health Agency of Canada, National Laboratory for HIV
Immunology, Winnipeg, Canada
Presenting author email: tball@cc.umanitoba.ca
Background: For 26 years a group of HESN women from Nairobi,
Kenya who can be epidemiologically described as relatively resistant
to HIV infection have provided clues towards the identification of
natural correlates of protection against HIV-1 infection. Studies of
these HIV-1-resistant women suggest they posses a unique mucosal
environment which includes the overexpression of specific antiproteases and a unique proinflamatory cytokine expression patern. Here
we describe how these factors contribute to protection against HIV
infection during mucosal transmission.
Methods: Cervical lavage fluid (CVL) from 277 women were collected
from 76 HIV-1-resistant, 120 HIV-1 uninfected, and 97 HIV-1 infected
women. CVL protein was analyzed both independently by SELDI-TOF
MS and as pooled groups by 2D-LC-FTICR MS. Of the more than 350
unique proteins identified 29 proteins were differentially expressed
( 2-fold cutoff) between HIV-1-resistant women and controls.
These findings were confirmed by traditional ELISA and quantitative
Western Blot (WB) analysis.
Results: The majority of overexpressed proteins were serpins, their
breakdown products (p 2.2 x 10 8), and other antiproteases, as
well as innate factors with known anti-HIV-1 activity. The overexpression of specific serpins and an epithelial-derived antiproteases
was confirmed by ELISA and WB (p 0.004, p 0.05, and p 0.02).
Underexpressed proteins in HIV-resistant women included inflammatory proteases and immune response factors. Cytokine/chemokine analysis revealed that antiprotease expression correlated with
pro-inflammatory cytokines (pB0.0001). However, this was independent of the elevated antiprotease expression observed in HIVresistant women who in fact expressed reduced levels of certain
inflammatory chemokines (p0.018).
Conclusion: HIV-1-resistant women have elevated acute phase
response antiproteases that may regulate inflammation in the female
genital tract. Coupled with elevated expression of anti-viral proteins,
this may provide a mucosal environment less susceptible to HIV-1.
These antiproteases might contribute to a natural protective environment against HIV-1-infection. Understanding this mechanism could
aid in microbicide or therapeutic development.
THPDA0103
Low magnitude and frequency of HSV-2-specific interferon
gamma-producing CD4 and CD8 T cell responses
detected in HIV-1 heterosexual discordant couples
T.N. Dieye1, A. Chentouffi2, M. Camara1, S. Sarr1, M.V. Tran2,
M. Seydi3, G. Dasgupta2, M. Fall1, G. Daneau4, P.A. Diaw1, L. Kestens4,
P.S. Sow3, S. Mboup1 and L. Benmohamed2
1
Cheikh Anta Diop University, Dakar, Senegal, Laboratory of
Immunology, Department of Bacteriology & Virology, Centre
Hospitalier Universitaire Le Dantec, Dakar, Senegal. 2University of
California Irvine, Laboratory of Cellular and Molecular Immunology,
The Gavin Herbert Eye Institute and Department of Ophthalmology,
Irvine, United States. 3Cheikh Anta Diop University, Dakar, Senegal,
Centre Hospitalier Universitaire de Fann, Dakar, Senegal. 4Institute of
Tropical Medicine, Antwerp, Belgium, Department of Microbiology,
Laboratory of Immunology, Antwerp, Belgium
Presenting author email: tndieye@yahoo.co.uk
Track A Basic Science
Background: Herpes simplex virus type 2 (HSV-2), the most frequent
cause of genital ulcer disease (GUD), has been shown to play a more
important role than any other sexually transmitted infections (STIs)
in driving HIV prevalence in Africa. In turn, HIV-1 infection leads to
more frequent HSV-2 reactivations and shedding. The exact immune
mechanisms involved in this virological negative immuno-synergy
are unknown. In the present study we sought to assess whether HIV
co-infection would affects HSV-specific T cell immunity.
Methods: Nineteen HSV peptides, derived from HSV-2 glycoproteins
gB and gD, were used to analyze the frequency and the magnitude of
HSV-2-specific IFN-g-producing CD4 and CD8 T cell responses in
30 HSV-2 seropositive patients and 17 HSV-2 seronegative individuals
in a cohort of heterosexual Senegalese HIV-discordant couples, using
ELISpot assay. HIV RNA viral load has been run for HIV infected
subjects and CD4 count ran for all subjects using a flow cytometry
method.
Results: The magnitude and frequency HSV-2-specific T cell responses was compared between 21 HSV-2 co-infected with HIV-1 and
9 HSV-2 mono-infected individuals. A significantly higher magnitude
of IFN-g-producing T cell responses were observed in HSV-2 infected
patients compared to seronegative individuals (median, 61 vs. 0
spots/106 PBMC, P 0.001). Moreover, twenty-four (80%) out of 30
HSV-2 seropositive patients showed significant HSV-2-specific IFN-gproducing T cell responses compared with only 6 (35%) out of 17
HSV-2 negative subjects (PB0.001). The HSV-2 mono-infected
patients showed significantly higher magnitude of HSV-2-specific T
cell responses compared to HSV/HIV co-infected patients (median,
140 vs. 42 spots/106 PBMC, P0.024).
Conclusion: Our finding suggest that co-infection with HIV-1 in HSV2-infected patients might be associated with reduced HSV-2 cellular
immune responses. However, the interaction between HIV and HSV-2
appears complex, and precise longitudinal studies will be required to
dissect their exact temporal relationship.
A10 - Mucosal immunity/defenses:
responses and dysfunction
TUAA0304
Oral serum-derived bovine immunoglobulin (SBI)
administration leads to duodenal gastrointestinalassociated lymphoid tissue (GALT) CD4 T-lymphocyte
increases and improved small intestinal absorption
function in an 8-week pilot study in patients with
HIV-enteropathy
D.M. Asmuth1, Z.-M. Ma2,3, A. Albanese4, S. Devaraj5, E. Hodzic2,
J.-C. Garcia1, T.H. Knight1, N.M. Flynn1, S. Mann1,4, T. Yotter1,
E. Tsuchida6 and C.J. Miller2,3
1
University of California Davis Medical Center, Sacramento,
United States. 2University of California at Davis, Davis, United States.
3
Center for Comparative Medicine, Davis, United States. 4Mather
Veterans’s Administration Hospital, Mather, United States.
5
University of Texas Children’s Hospital, Houston, United States.
6
CARES Clinic, Sacramento, United States
Presenting author email: david.asmuth@ucdmc.ucdavis.edu
Background: HIV-infection leads to GALT CD4 T-cell depletion that
persists despite prolonged antiretroviral therapy (ART). SBI is a
medical food that neutralizes bacterial antigens and reduces gut
inflammation in animal models.
7
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Methods: Subjects on ART with diarrhea and a thorough negative GIworkup received SBI (EnteraHealth, Ankeny,IA,USA) 2.5 grams BID for
8 weeks. 4-hour urine disaccharide gut permeability and absorption
test and duodenal biopsies were obtained before and at 8-weeks.
Immunohistochemistry for CD3/CD4 was performed on biopsies and
flow cytometry was performed on duodenal single-cell suspensions
and PBMCs for lymphocyte subsets. Markers of bacterial translocation and cytokine levels were measured in plasma. Stool was collected for 16S rDNA quantification and sequencing. Median values
(interquartile ranges) and nonparametric analysis are reported.
Results: All 8 subjects experienced resolution of GI-related symptoms. D-xylose absorption increased in 7/8 subjects and in those
with improvement, the absorption levels increased from 31.4 mgs
(28.5, 38.8) to 41.5 mgs (33.7, 45.2)(p 0.016). Gut permeability was
normal before [0.024% (0.0, 0.048)] and after [0.032% (0.0, 0.047)]
intervention (normal B0.050%). Median duodenal tissue CD4 Tcell% was unchanged at 16%. Lipopolysaccharide, sCD14, IFN-g, IL10, IL-12p70, IL-8, IL-6, and TNF-a were in the normal range before
and unchanged after 8-weeks. Absolute lamina propria CD3/CD4 Tcell density increased from 199 cells/mm2 (129, 253) to 274 (216,
370)(p 0.062) after 8-weeks of SBI [normal values 836 cells/mm2
(474, 1050)]. Previous studies show increases of less than 50 cells/
mm2 after 9 months of ART. Log10 absolute 16S rDNA stool
quantification was unchanged between baseline and week-8 [7.125
cp/gm (6.34, 7.5) to 7.415 (6.4, 7.56)].
Conclusion: SBI improved GI absorption and increased GALT CD4
T-lymphocyte density. Further research is needed to demonstrate
whether alterations in gut microbiota or inflammatory milieu impact
mucosal immunology. Longer studies are needed to examine the
mechanisms of SBI in GALT immune reconstitution and improvement
in HIV enteropathy.
TUAA0305
Improved intestinal immunity and cytotoxic potential of T cells
in interleukin (IL)-21 treated SIV-infected rhesus macaques
S. Pallikkuth1, L. Micci2, Z. Ende2, R. Iriele2, B. Cervasi2, J. Else2,
G. Silvestri2, F. Villinger2, S. Pahwa1 and M. Paiardini2
1
University of Miami Miller School of Medicine, Miami,
United States. 2Emory University, Yerkes National Primate Research
Center, Atlanta, United States
Presenting author email: mirko.paiardini@emory.edu
Background: Interleukin (IL)-21 regulates three immunological functions - Th17 cell homeostasis, differentiation of memory B cells and
antibody-secreting plasma cells, and long-term maintenance of
functional CD8T-cells - that are compromised in pathogenic HIV
and SIV infections. Since IL-21 availability is reduced during infection,
we hypothesized that in vivo administration of IL-21 might be
beneficial for HIV infected humans.
Methods: We infected 12 rhesus macaques with SIVmac239 (i.v.), and
then treated 6 of them with rhesus rIL-21-IgFc (50mg/kg, s.c., once
weekly for 5 weeks) during the early infection (from day 14 to 42
post-infection). Effects of IL-21 on viral load, immune activation,
homeostasis of T-cells and their main subsets as well as T-cell
cytotoxic potential have been evaluated in blood and mucosa by qPCR, IHC, and flow cytometry up to 6 months post-infection. MannWhitney test and Spearman correlation were used for statistical
analyzes.
Results: IL-21 treatment was safe and did not increase plasma
viral load or systemic immune activation. Compared to untreated
animals, IL-21 treatment resulted in (i) increased expression of
Perforin and GrB in total and virus specific CD8T-cells of various
anatomical sites (PB0.05); and (ii) improved mucosal immunity,
Track A Basic Science
with higher levels of Th17 CD4T-cells (P B0.01) during the
treatment period. Interestingly, improved Th17 homeostasis was
associated with limited proliferation of intestinal CD4and CD8Tcells (PB0.05) and reduced plasmatic level of LPS (PB0.01) at 6
months post-infection.
Conclusion: IL-21 treatment during acute SIV infection beneficially impacts on the cytotoxic potential of T-cells and intestinal
immunity - including increased homeostasis of Th17 cells, reduced
levels of T-cell activation and limited microbial translocation - without
undesirable effects on viral load. IL-21 should be further explored as a
potential immunomodulator to be used in HIV infection in the context
of ART or as part of new HIV vaccine strategies.
WEPDA0103
Induction and maintenance of HIV-1-specific immune
responses in exposed seronegative (ESN) women of
serodiscordant couples from southern India
S. Solomon1, K.G. Murugavel1, R. Vignesh1, D. Bella1, R. Shoba1,
S. Poongulali1, N. Kumarasamy1, A. Landay2, S.S. Solomon1,3,
C.R. Swathirajan1, P. Balakrishnan1, S. Cu-Uvin4, K.H. Mayer5 and
B.L. Shacklett6
1
YRG Centre for AIDS Research and Education (YRG CARE)
Chennai, India. 2Rush University Medical Center, Chicago
United States. 3Johns Hopkins University School of Medicine,
Baltimore, United States. 4Brown University-The Miriam
Hospital, Rhode Island, United States. 5Harvard Medical
School-Beth Israel Deaconess Medical Center/The Fenway Institute,
Boston, United States. 6University of California-Davis, Davis
United States
Background: The majority of new HIV infections are acquired via heterosexual transmission. Certain individuals remain seronegative despite repeated high-risk exposure to HIV.The correlates of protection in
exposed seronegative(ESN) individuals remain unclear. The purpose
of this study was to determine the breadth and persistence of HIVspecific CTL responses in blood and cervical mucosa of ESN women.
Methods: The ESN cohort included 30 female partners of antiretroviral naı̈ve HIV men. ESN women were followed longitudinally
for 3-6 months. Controls included sero-concordant couples (n17)
and low-risk seronegative women (n 30). PBMC and mucosal
mononuclear cells (MMC) from cervical cytobrush were stimulated with HIV Gag and Env (Clade C) peptide pools; IFN-g production
was measured by intracellular cytokine staining. IFN-g production
by 0.1% of cells after background subtraction was considered positive. Samples with B400 total events and/orB10 positive events
were considered equivocal.
Results: At baseline, PBMC from 2 of 30(7%) ESN and MMC from 3 of
17 (18%) ESN responded to stimulation with HIV antigens. During
follow-up, 17 PBMC and 7 MMC samples were analyzed. Of these,
PBMC from 2 ESN(12%) and MMC from 1 ESN(14%) responded to
Gag and/or Env. In HIV women of concordant couples, responses
were detected in 50% of PBMC and 40% of MMC. No responses were
detected in low-risk controls. Median CD4 and plasma viral loads of
male partners of ESN women were 477 cells/mL (range 238-1,090)
and 26,300 copies/mL (range 400-750,000); values for male partners
in sero-concordant couples were 520(range 132-1,321) and 31,850
(range 400-492,000).
Conclusion: These findings confirm that HIV-specific T-cell responses
can be detected in PBMC and MMC from ESN women. These
responses could play a protective role; however, they may simply be
indicative of antigen exposure. A small percentage of ESN women
continued to show positive responses upon longitudinal follow-up,
arguing against a protective role for these responses.
8
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
A12 - Mechanisms of activation /
inflammation and impact in pathogenesis
TUAA0104
Glut1: establishing a new paradigm for HIV-1 infection by
regulating glucose metabolism and activation in CD4 T
cells in HIV-1-positive subjects
C.S. Palmer1,2, J. Zhou1, S. Saleh1, L. Lam1, A. Hearps1,3, A. Maisa1,
C. Pereira1, S. Lewin1,3,4, A. Jaworowski1,3, J.M. McCune5 and
S. Crowe1,3,4
1
Burnet Institute, Virology, Melbourne, Australia. 2University of New
South WalesSchool of Medical Sciences, Sydney, Australia. 3Monash
University, Melbourne, Australia. 4Alfred Hospital, Melbourne,
Australia. 5Division of Experimental Medicine, University of
California, San Francisco, School of Medicine, San Francisco,
United States
Presenting author email: c.palmer@unsw.edu.au
Background: A characteristic feature of the early phase of mammalian cells to metabolic stress is an increase in the rate of glucose
uptake and metabolism. Glucose transporter 1 (Glut1) is the major
glucose transporter in T cells and its expression is increased on
CD4T cells during chronic HIV-1 infection in vivo (Palmer et al.,
Abstract 1, IAS, 2012). We therefore seek to determine the impact of
increased Glut1 expression on glucose metabolism in CD4T cells
from HIV-1-infected subjects.
Methods: The cell surface expression of Glut1 and glucose uptake (2NBDG) was monitored in CD4T cells from HIV-1 infected treatment
naı̈ve or HIV- controls subjects by flow cytometry. Hexokinase and
glycolytic activity was measured by the intracellular concentrations
of Glucose-6-phosphate (G-6-P) and L-lactate, respectively. Intracellular PTEN, pAkt (T308) and pAkt (S473) levels determined PI3KmTOR activity. In vitro HIV-1 infection was performed on PBMCs
activated with anti-CD3/CD28 microbeads and IL-7 and incubated
with the CXCR4-using NL4.3-GFP virus.
Results: Basal glucose uptake, G-6-P, L-lactate, intracellular p-Akt
(T308) and p-Akt (S473) were significantly higher in CD4Glut1
vs CD4Glut1- cells. This corresponded with an overall increased
glucose uptake and glycolysis and lower levels of PTEN expression
in CD4T cells from HIV-1subject vs seronegative individuals.
Anti-CD3/CD28-induced Glut1 expression on CD4 T cells was
sensitive to specific inhibition of the Class1B PI3K-y and mTORC1
pathways which also blocked HIV-1 infection of CD4T cells in
vitro.
Conclusion: CD4T cells from HIV-1 infected patients have increased
glucose uptake and glycolytic activity mediated at least in part by the
PI3k-y-mTORC1 pathway. Increased Glut1 cell surface expression and
glycolysis in CD4T cells may increase their susceptibility to HIV-1
infection and foster their depletion due to hypermetabolism.
Approaches to normalize Glut1 expression or glycolysis in CD4T
cells may offer a platform for interventions to slow HIV-1 disease
progression.
WEAA0204
HIV-induced CD4 T cell depletion: an innate host defense
gone awry?
G. Doitsh, N. Galloway, K. Monroe, Z. Yang, O. Zepeda and
W.C. Greene
The J. David Gladstone Institutes, Virology and Immunology, San
Francisco, United States
Presenting author email: gdoitsh@gladstone.ucsf.edu
Track A Basic Science
Background: Progressive depletion of CD4 T cells is a hallmark of
AIDS yet the underlying mechanism remains poorly understood. In
human lymphoid cultures, most of the dying cells correspond to
abortively infected resting CD4 T cells (Cell 143:789-901,2010). We
have now studied how these cells die.
Methods: Human lymphoid aggregated cultures (HLACs) prepared
with human tonsil and spleen were used to recapitulate many of the
conditions encountered by HIV in vivo. CD4 T cell death is prominent
in HLAC following viral infection.
Results: 95% human lymphoid CD4 T cells that die in HLAC are
abortively, not productively, infected. These nonpermissive resting
cells accumulate incomplete cytosolic viral transcripts that trigger an
innate immune response resulting in interferon-beta production and
activation of caspase-3 and caspase-1. Most cells die as a consequence of caspase-1-mediated pyroptosis, an intensely inflammatory
form of programmed cell death where cytoplasmic contents and
pro-inflammatory cytokines (IL-1b) are released. Unexpectedly,
HIV-induced CD4 T-cell death and release of inflammatory mediators
can be blocked by addition of certain oral sulfonylureas like
glimepiride that inhibit P2X7 ion channels, and are FDA-approved
for the treatment of type II diabetes.
Conclusion: 1. Abortively infected lymphoid CD4 T cells do not die
due to the action of an HIV virulence factor(s), but rather because of
host innate immune response launched against viral DNA produced
in these cells.
2. This response likely evolved to protect the host from spread of
infection, but the involvement of pyroptosis appears to trigger
additional rounds of cell recruitment, infection, cell death, and
inflammation.
3. CD4 T-cell depletion is blocked by P2X7 inhibitors that may
interfere with pyroptosis. Such agents might be clinically useful in
combination with classical antiretrovirals, particularly in HIV-infected
subjects displaying rapid progression of disease or broad drug
resistance.
TUPDA0102
Elite controllers show a unique Tryptophan
immunosuppressive catabolism
M. Patel1, M.-A. Jenabian1,2, B. Lebouché1, M.-J. Brouillette1,3,
C. Tremblay4, I. Kema5, M.-R. Boulassel1,6 and J.-P. Routy1,2,6
1
Chronic Viral Diseases Service of the McGill University Health
Centre, Montreal, Canada. 2Research Institute of the McGill
University Health Centre, Montreal, Canada. 3Department of
Psychiatry, Royal Victoria Hospital, McGill University Health Centre,
Montreal, Canada. 4Department of Microbiology and Immunology,
Université de Montréal, Montreal, Canada. 5Department of
Laboratory Medicine, University Medical Center, Groningen,
Netherlands. 6Division of Hematology, McGill University Health
Centre, Montreal, Canada
Presenting author email: jean-pierre.routy@mcgill.ca
Background: Increased Tryptophan (Trp) catabolism into kynurenine
(Kyn) and/or 3-hydroxykynurenine (3OH-kyn) by indoleamine 2,3
dioxygenase (IDO), contributes significantly to the persistent immune
activation during HIV infection and plays a detrimental role in T cell
responses in advanced AIDS. We herein studied Trp catabolism in
elite controllers comparing to other well established groups of HIV
patients with different disease outcomes.
Methods: Plasma samples from elite controllers (EC) (n 21),
ART-naive (n96), ART-successfully treated (ST) (n 18), and
healthy controls (n 51) were collected. All these groups were
standardized for nutritional status (albumin levels and body
mass index). Levels of Trp, Kyn and 3OH-kyn were measured using
9
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
isotope dilution tandem mass spectrometry and the markers of Trp
catabolism (Kyn/Trp and 3OH-kyn/Trp ratios) were correlated to
clinical data.
Results: In ART-naive patients, viral load was positively associated with
Kyn, 3OH-kyn levels and the markers of Trp catabolism (p B0.0001).
In addition, these patients presented significantly lower Trp levels
compared to controls (p 0.0002) and to ST (p 0.042). Accordingly,
both Trp metabolites and Kyn/Trp and 3OH-kyn/Trp ratios were more
enhanced in ART-naive vs ST and controls. EC who spontaneously
control viral load, had the same plasma Trp levels as ART-naive
(mean 46.15 vs 46.6 mmol/L, p0.874) but lower than controls and
ST (54.37 mmol/L, p 0.018 and 52.57 mmol/L, p0.138 respectively).
Interestingly, EC had significantly lowered Trp metabolites such as Kyn
and 3OH-kyn levels compared to ART-naive patients (p 0.0005 and
p0.025 respectively). In contrast, EC had similar Kyn and 3OH-kyn
levels to Control and STsuggesting a unique Trp metabolism associated
with suppressed viral replication.
Conclusion: Elite controllers show a unique regulation of immunosuppressive Tryptophan catabolism. These findings may be relevant
for HIV viral control and eradication.
A13 - Mechanisms of T cell depletion and
dysfunction
MOAA0205
IL-7 suppresses transcription of the IL-7 receptor alpha
(CD127) gene in human CD8 T cells by inducing the
expression of a STAT5-dependent transcriptional repressor
F. Al-Ghazawi1,2, E. Faller1,2, P. Parmar1,2, J. Kakal1 and
P. MacPherson1,2,3
1
University of Ottawa, BiochemistryMicrobiology and Immunology,
Ottawa, Canada. 2Ottawa Hospital Research InstituteChronic and
Infectious Diseases, Ottawa, Canada. 3Ottawa Hospital, Ottawa,
Canada
Presenting author email: feras_ghazawi@hotmail.com
Background: In view of the role interleukin (IL)-7 plays in T-cell
survival, homeostasis and function it is no surprise expression of the
IL-7 receptor alpha-chain (CD127) is tightly regulated. We previously
showed that expression of CD127 is suppressed on CD8 T-cells in
HIV patients and that this suppression is mediated by both IL-7
and the HIV Tat protein. IL-7 down-regulates CD127 transcripts and
surface protein through two distinct mechanisms. In this study we
examine the mechanism by which IL-7 down-regulates the CD127
gene at the level of transcription.
Methods: CD8 T-cells from HIV-negative volunteers were
treated with IL-7 (0.110 ng/ml) in the presence or absence of
various inhibitors. CD127 transcripts were quantified by qPCR.
STAT-5 phosphorylation was measured by flow cytometry. Nuclear
run-on assays were utilized to measure the rate of CD127 gene
transcription. Candidate CD127 repressors were identified using
PCR arrays, qPCR, Western and siRNA-mediated gene knock-down
assays.
Results: IL-7 attenuates levels of CD127 transcripts in CD8 T-cells
in a time- and dose-dependent manner. Both the full-length
transcript and the splice-variant encoding the secreted isoform of
CD127 are suppressed by IL-7. We show by nuclear run-on assay that
IL-7 suppresses the rate of transcription of the CD127 gene and
found no evidence that IL-7 affects the stability of CD127 mRNA.
Track A Basic Science
Further, the suppression of CD127 transcripts is dependent on JAK
kinase activity and phosphorylation of STAT-5 but not STAT-3.
Notably, cycloheximide blocked IL-7’s ability to down-regulate
CD127 transcripts suggesting IL-7 stimulates the de novo synthesis
of a transcriptional repressor which in turn suppresses CD127 gene
transcription. We recently identified several candidate repressors
using PCR arrays and are currently examining their involvement in
the transcriptional suppression by siRNA-mediated knockout experiments.
Conclusion: Upon binding to its receptor, IL-7 activates the JAK/STAT5 signaling and induces the expression of a transcriptional repressor
which suppresses CD127 gene transcription.
WEAA0205
Suppressor of cytokine signalling (SOCS) proteins are
induced by IL-7 and the interaction of SOCS proteins with
the IL-7 receptor alpha (CD127) may play a role in regulating
CD127 expression in human CD8 T cells
F. Al-Ghazawi1,2, P. Parmar1,2, E. Faller1,2, S. Sugden1,2, N. Sant3 and
P. MacPherson1,2,3
1
University of Ottawa, Biochemistry, Microbiology and Immunology,
Ottawa, Canada. 2Ottawa Hospital Research Institute, Chronic and
Infectious Diseases, Ottawa, Canada. 3Ottawa Hospital, Ottawa,
Canada
Presenting author email: feras_ghazawi@hotmail.com
Background: Interleukin (IL)-7 plays essential roles in T-cell development, homeostasis and activation. Disruption of this cytokine
pathway likely contributes to HIV-induced immune deficiency. We
previously showed that IL-7 and the HIV Tat protein reduce the halflife of the IL-7 receptor alpha-chain (CD127) in human CD8 T-cells but
the mechanism directing CD127 to the proteasome is not yet
understood. In this study we examined roles of SOCS proteins in
regulating CD127 expression.
Methods: CD8 T-cells isolated from healthy HIV-negative volunteers
were treated with IL-7 (0.110 ng/ml) in the presence or absence of
various inhibitors. SOCS1-7 and CIS transcripts were examined by
qPCR and protein expression was measured by Western. The
interaction of SOCS proteins with CD127 was examined by Co-IP.
Surface CD127 protein expression was measured by flow cytometry.
Intracellular localization of SOCS and CD127 protein was examined
by confocal microscopy.
Results: IL-7 induces the expression of SOCS1-3 and CIS transcripts in
CD8 T-cells via the JAK/STAT-5 signaling pathway in a time- and dosedependent manner with SOCS2 transcripts increasing 300-fold within
3 hours. While induction of SOCS2 and SOCS3 mRNA was transient,
SOCS1 and CIS transcripts remained elevated over baseline for at
least 48 hours. Western blot analysis confirmed increased protein
expression of the induced SOCS genes. Preliminary data on CD8 Tcells isolated from HIVpatients indicate that the IL-7-mediated upregulation of SOCS transcripts is significantly decreased compared to
healthy controls. IL-7 induces rapid phosphorylation and internalization of CD127 followed by proteasomal degradation. By Co-IP
we show SOCS proteins induced by IL-7 physically interact with
CD127 and study their cellular localization by confocal microscopy.
We hypothesize this interaction directs the receptor to the proteasome.
Conclusion: IL-7 induces the expression of SOCS1-3 and CIS genes
through the JAK/STAT-5 pathway. Through physical interaction with
CD127, SOCS proteins may direct CD127 to the proteasome for
degradation.
10
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
A14 - Pathogenesis in gut, lymphoid
tissues and bone marrow
WEAA0202
Differential SIV infection patterns of lymph node-resident
CD4 T cells distinguishes progressive from nonprogressive
SIV infection
C. Vinton1,2, J. Brenchley1,2, B. Tabb3, X.P. Hao4, V.M. Hirsch2,
M. Paiardini5, J. Lifson3, G. Silvestri5 and J.D. Estes3
1
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Program in Barrier Immunity and Repair and
Immunopathogenesis Unit, Bethesda, United States. 2National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, Laboratory of Molecular Microbiology, Bethesda
United States. 3National Cancer Institute, National Institutes of
Health, AIDS and Cancer Virus Program, Frederick, United States.
4
National Cancer Institute, National Institutes of Health, Pathology
and Histotechnology Laboratory, Frederick, United States. 5Emory
University, Atlanta, United States
Presenting author email: vintonca@mail.nih.gov
Background: Nonhuman primate natural hosts for simian immunodeficiency viruses (SIV) develop a non-resolving chronic SIV infection,
but do not develop AIDS. While several hypotheses, such as downmodulation of immune activation and differential surface expression
of SIV receptors, have been suggested as putative mechanisms to
explain the nonprogressive nature of SIV infection in natural hosts,
mechanisms underlying high and maintained levels of plasma viremia
without apparent loss of target cells in natural hosts remain unclear.
Methods: Here, we have used flow cytometric sorting, quantitative
real-time PCR, immunohistochemistry, and in situ hybridization to
study viral infectivity and production within subsets of peripheral
blood and lymph node-resident CD4 T cells in cohorts of chronically
SIVsmm-infected sooty mangabeys and SIVsmE53-infected rhesus
macaques.
Results: We find: (1) infection frequencies among PB and LN-resident
CD4 T cells in chronically SIVsmE543-infected RM are significantly
higher than those in SIVsmm-infected SM; (2) differential virus
targeting is observed among anatomical LN niches and among
individual CD4 T cell subsets in SIV-infected RM and SM; (3) lymph
node resident TFH cells are preferentially SIV-infected in RM, but
these cells are not preferentially infected in SM and; (4) infectivity of
central and effector memory CD4 T cells is associated with plasma
viremia in RM while infectivity of only effector memory CD4 T cell
infectivity is associated with plasma viremia in SM.
Conclusion: These data provide mechanistic insights into the
maintenance of immunological function among chronically SIVinfected natural hosts for SIV, provide an explanation as to how
natural hosts are able to maintain high levels of plasma viremia
without apparent loss of target cells, and may lead to novel gene
therapy interventions to recapitulate the natural host phenotype to
animals that are susceptible to SIV-induced disease.
A23 - Regulation of gene expression and
latency
TUAA0102
Third generation long-read sequencing of HIV-1 transcripts
discloses cell type specific and temporal regulation of RNA
splicing
Track A Basic Science
F. Bushman1, S. Sherrill-Mix1, K. Ocwieja1, R. Mukherjee1, M. Brown2,
J. Chin2, R. Custers-Allen1, P. David3, J. Olson3, K. Travers2 and
E. Schadt2
1
University of Pennsylvania School of Medicine, Department of
Microbiology, Philadelphia, United States. 2Pacific Biosciences, Menlo
Park, United States. 3Raindance Technologies, Lexington
United States
Presenting author email: bushman@mail.med.upenn.edu
Background: Transcription of the HIV-1 genome yields an initial premRNA which undergoes complex alternative splicing to produce over
multiple spliced mRNAs. Analysis of host cell factors important for HIV
replication by genome-wide siRNA screens has emphasized that HIV
replication is extremely sensitive to the complement of available
splicing factors, suggesting that HIV splicing may be an attractive target
for therapeutic intervention. Here, we have used single molecule
amplification and third generation sequencing to characterize splice
patterns for the patient isolate HIV89.6 under different conditions.
Methods: We infected HOS cells or primary T-cells and carried out
single molecule PCR in emulsionsto minimize competition among
amplicons. We then used Pacific Biosciences single molecule
sequencing to analyze message populations.
Results: Primary sequence read lengths averaged 1.6 Kb, and 5%
of reads were over 3.8 Kb. Over 100 different messages was
documented, more than doubling the previous number. The HIV
sequence reads confirmed all of the known major splice junctions
and identified new splice junctions, which create new ORFs in the
89.6 isolate. The presence of these new transcripts was confirmed
using RT-PCR. The ORFs encode a novel form of Tat with an altered
carboxy terminus and a Rev-Nef fusion (dubbed ‘‘Ref’’) containing
the amino terminal helix of Rev and the carboxy terminal portion of
Nef. Using this assay, we found that HIV splicing differed between
different cell types, differed between different human donors, and
changes over time after infection.
Conclusion: These data illustrate how the diversity and promiscuity
of splicing in HIV allows the virus to respond to different cellular
environments and provides a continuous supply of evolutionary
novelty that can potentially serve as a substrate for natural selection.
WEPDA0205
HIV-1 Tat protein up-regulates human cellular miRNAs
involved in T cell apoptosis: requirement of Tat second exon
M. Sánchez del Cojo, M.R. López-Huertas, E. Mateos, M. Coiras and
J. Alcamı́
National Centre of Microbiology, Instituto de Salud Carlos III, AIDS
Immunopatology Unit, Majadahonda, Spain
Presenting author email: msdelcojo@isciii.es
Background: HIV-1 infected cells have evolved strategies to delay
apoptosis but the exact mechanism is unknown. One explanation
could be the enhancement of Bcl-2 levels. MicroRNAs (miRNAs) are
small non-coding RNAs that participate in the innate immune
response. Several cellular miRNAs target viral mRNAs, leading to a
decreased viral replication, but viruses may also counteract this
effect. In the case of HIV-1, Tat has been described as an RNAi
suppressor, although this statement remains controversial. To get
better insight into this issue and into the effect of Tat in protection to
apoptosis, we have analyzed the miRNA expression pattern in Jurkat
cells expressing different forms of Tat.
Methods: The miRNA expression profile of Jurkat cells with stable
expression of HIV-1 full-length Tat101 (two-exon protein) or Tat72
(exon 1 isoform) was analyzed with a two color-based array of miRNAs
(Exiqon). Differences in miRNA expression were then confirmed by
qRT-PCR.
11
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Results: Global down-regulation of cellular miRNAs due to the
expression of Tat was not observed. Instead, several specific miRNAs
were dis-regulated due to the expression of Tat101 or Tat72, although
the expression of the second exon granted a higher modification. We
confirmed that cellular miR-21 and miR-222 were up-regulated in
Jurkat Tat101 cells. miR-21 plays an important role in apoptosis. Since
a higher resistance to FasL-mediated apoptosis was observed in Jurkat
Tat101, we established a correlation between this protection and the
increased levels of Bcl-2 in Jurkat Tat101. Regarding miR-222, it
regulates cell cycle progression. In agreement with this, Jurkat Tat101
cells showed less proliferation capacity than control cells.
Conclusion: HIV-1 Tat does not show a general RNAi suppressor
activity but it increases specifically several human miRNAs, conferring cells protection to apoptosis. This phenomenon was dependent
on the expression of full-length Tat.
A25 - Cellular elements necessary for HIV
replication
TUAA0101
Discovery of novel transcription factors present only in
infected cells
G. Sampey1, R. Van Duyne1,2, I. Guendel1, E. Gregg1, N. Shafagati1,
M. Tyagi1, R. Easely1, Z. Klase3, F. Romerio4, M. Iglesias-Ussel4,
S. Nekhai5, K. Kehn-Hall1 and F. Kashanchi1
1
George Mason University, NCBID, Manassas, United States. 2George
Washington University, Washington, United States. 3National
Institutes of Health, Bethesda, United States. 4University of Maryland
School of Medicine, Baltimore, United States. 5Howard University,
Washington, United States
Presenting author email: fkashanc@gmu.edu
Background: Throughout the years many labs have discovered
important factors that contribute to the transcription of HIV-1. Most
of these factors have been well characterized and their significance
has been validated. Some of the critical factors involved in Tat
activated transcription include RNA Pol II (associated with LTR),
chromatin remodeling complexes (i.e. SWI/SNF), acetyltransferases
(i.e. CBP, p300, pCAF), NFkB and components of pTEF-b. Surprisingly,
almost none of the published literature has focused on finding these
factors as complexes from genuine HIV-1 infected cells. Here we
show presence of undiscovered complexes unique to HIV-1 infected
cells which may serve as targets of inhibition.
Methods: We utilized a combination of HIV infected cell lines and
primary latent cells (both T-cells and monocyte/macrophages) to
define changes of protein complexes in infected cells. We utilized large
quantities of infected cell lysates for size-exclusion chromatography to
find novel kinases (i.e. cdk9/T complexes), and chromatin remodeling
complexes, among others in presence of high salt (500 mM).
Results: We found that there are novel cdk9/T complexes ranging
from 2 MDa to 300 KDa present only in T-cells that produce virus.
Other components of the pTEF-b are also examined and found to be
mostly unchanged in infected vs uninfected cells. Other novel
complexes present only in infected cells included kinases for the
NFkB pathway and SWI/SNF proteins. Many of these proteins are
extremely stable and are targets of drug inhibition. Using a small panel
of drugs, we find that many of the kinases utilized for transcription of
HIV-1 have varying IC50s depending on the size of the complex and
their protein partners.
Conclusion: HIV-1 infected cells contain many novel protein complexes that are yet to be discovered. Here we use a simple method of
Track A Basic Science
size exclusion to discover novel complexes that could potentially be
used as targets of inhibition in therapeutics.
A27 - Viral mechanisms of persistence
and latency
MOAA0102
Myeloid dendritic cells and HIV latency in resting T cells
N. Kumar1,2, V. Evans1,2, S. Saleh1,2, C.F. Pereira1,2,3, P. Ellenberg1,2,
P.U. Cameron1,2,4 and S.R. Lewin1,2,4
1
Monash University, Department of Medicine, Melbourne, Australia.
2
Burnet Institute, Melbourne, Australia. 3Monash University, Monash
Micro Imaging, Melbourne, Australia. 4Alfred Hospital, Infectious
Disease Unit, Melbourne, Australia
Presenting author email: nakum1@student.monash.edu
Background: Latently-infected resting CD4 T-cells are a major
barrier to the eradication of HIV infection. These cells are enriched in
lymphoid tissue compared to blood. We hypothesized that interactions between dendritic cells (DC) and resting CD4 T-cells are
critical for the establishment and maintenance of HIV latency.
Methods: Resting CD4 T-cells labelled with eFluor670 were
cultured alone or with syngeneic DC for 24h prior to infection with
a CCR5-tropic, EGFP-reporter virus. Non-proliferating (eFluor670hi),
non-productively-infected (EGFP-) CD4 T-cells were sorted on day
5 post-infection. Latent infection was re-activated and amplified by
co-culturing sorted cells with mitogen stimulated PBMC.
Results: Infection of resting CD4 T-cells in the presence of myeloid
(m)DC significantly increased latent infection of non-proliferating
CD4 T-cells compared to infection of T-cells cultured alone
(p 0.0005, n 11). Latent infection was not increased in resting
CD4 T-cells co-cultured with plasmacytoid DC (n 11) or monocytederived-dendritic-cells (n 2). Co-culture of mDC with memory
(CD45RO) CD4 T-cells but not naı̈ve (CD45RO-) CD4 T-cells
resulted in latency (n6). eFluor670hiEGFP- CD4 T-cells that had
been co-cultured with mDC showed a significant increase in the
expression of CD69 (p 0.01, n8) and PD-1 (p 0.007, n10), but
did not express HLA-DR or Ki67. Treatment of the mDC-T-cell
co-cultures with blocking antibodies to the chemokines CCL19 and
CXCL10 (shown to induce latent infection in resting CD4 T-cells); the
chemokine receptor CXCR3; or the adhesion molecule LFA-1 (binds to
ICAM) led to no changes in the frequency of latently-infected CD4 Tcells (n 5). When mDC-T-cell contact was prevented using transwells
the number of latently-infected CD4 T-cells was reduced (n 3).
Conclusion: mDC play a key role in the establishment and/or
maintenance of HIV latency in resting memory CD4 T-cells. Our
results suggest this is likely to be mediated through DC-T-cell contact
via alternative pathways to ICAM-LFA-1 binding.
TUAA0201
Unique regulatory mechanisms of CNS-derived HIV-1 LTRs
associated with latency
L. Gray1,2, D. Cowley1,3, E. Crespan1, C. Welsh1,4, C. Mackenzie1,5,
P. Gorry1,3,6, S. Wesselingh1,7 and M. Churchill1,3,4
1
Burnet Institute, Centre for Virology, Melbourne, Australia. 2Monash
University, Department of Biochemistry and Molecular Biology,
Clayton, Australia. 3Monash University, Department of Medicine,
Clayton, Australia. 4Monash University, Department of Microbiology,
Clayton, Australia. 5Monash University, Department of Immunology,
12
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Melbourne, Australia. 6The University of Melbourne, Department of
Microbiology and Immunology, Melbourne, Australia. 7South
Australian Health and Medical Research Institute, Adelaide, Australia
Presenting author email: lachlang@burnet.edu.au
Background: HIV-1 penetrates the central nervous system (CNS)
during early infection, establishing a viral reservoir. While macrophages and microglia represent the sites of productive HIV-1
infection, astrocytes undergo a restricted/latent infection. We
recently demonstrated that astrocytes are extensively infected and
may therefore constitute a significant potential reservoir of HIV-1
within the CNS. Here, we analyzed HIV-1 promoters (LTR) from
matched CNS and non-CNS compartments to determine their role in
virus restriction within CNS-derived cells. Determining the regulatory
mechanisms of CNS-derived LTRs is essential to understanding the
CNS as a HIV-1 viral reservoir, and in developing strategies aimed at
HIV-1 eradication.
Methods: HIV-1 LTR sequences from a cohort of HIV-1 autopsy
subjects consisting of matched CNS- and non-CNS-derived isolates
were examined and their activity was determined in T-cells and SVG
astrocyte cells. Electrophoretic mobility shift assays (EMSA) were
used to analyze transcription factor binding activity within the core
and basal promoter regions of the LTR.
Results: CNS-derived LTRs demonstrated restricted basal transcriptional activity in both T-cells and SVG cells, and non-CNS-derived
LTRs showed decreased activity in SVG cells. Restricted basal
activity mapped to the three Sp binding motifs, previously shown
to be essential for both Tat-independent and Tat-dependent activation of the LTR in T-cells. Further repression in astrocytes
was observed due to elevated levels of the repressor Sp3 in SVG
cells.
Conclusion: The reduced transcriptional activity observed for CNSderived HIV-1 promoters was found to correlate with a reduction in
Sp1 binding, which mapped to mutations within the core Sp binding
motif. Transcriptional activity in SVG cells was further regulated by
Sp3, which outcompeted Sp1 for Sp-motif binding. These data
suggest that CNS-derived viruses have a reduced capacity to initiate
viral transcription in astrocytes and highlights that unique transcriptional mechanisms exist within the CNS, ultimately affecting the fate
of viral infection and the development of latency.
TUAA0202
Complete transcriptome analysis of latently infected CD4
T cells
M. Iglesias-Ussel1, L. Marchionni2 and F. Romerio1
1
University of Maryland School of Medicine, Institute of Human
Virology, Baltimore, United States. 2Johns Hopkins University, Sidney
Kimmel Comprehensive Cancer Center, Baltimore, United States
Presenting author email: fromerio@ihv.umaryland.edu
Background: Latent reservoirs of HIV-1 consist of cells harboring
dormant, stably integrated viral genomes that can be reactivated
after cell stimulation. Latent HIV-1 evades immune responses and
resists anti-retroviral therapy. CD4 T cells are the major reservoir of
latent HIV-1. These cells are very rare and lack distinctive markers,
which has hindered their characterization.
Methods: We developed an in vitro model suitable to investigate
HIV-1 latency in CD4 T cells. In our system CD4 T cells are
activated with dendritic cells and antigen, infected in vitro with HIV1, and then brought back to quiescence through a resting phase in
the presence of interleukin-7. During the resting phase, the latently
infected cells generated with our system lack expression of activation
markers; do not undergo cellular proliferation and do not sustain
Track A Basic Science
viral replication. We sorted latently infected and uninfected cells
from the same cell culture at the end of the resting phase, and
profiled their entire transcriptome.
Results: The results of this microarray analysis revealed profound
differences between latently infected and uninfected cells derived
from the same culture. First, a number of genes involved in all major
cellular metabolic pathways are down-modulated in latently infected
cells. Second, several messengers involved in gene expression
(including chromatin organization, transcription, translation, posttranslational modification, transport and assembly) are also downregulated in latently infected cells. Third, genes involved in signal
transduction, cell activation, cell proliferation and cell cycle progression are down-modulated in latently infected cells. Finally, several
genes encoding cell surface molecules are differently expressed in
latently infected vs. uninfected cells.
Conclusion: The establishment of HIV-1 latency does not simply
entail suppression of HIV-1 expression, and the return to cell
quiescence. Rather, HIV-1 appears to exploit and/or promote
suppression of all cellular functions, leading to cell quiescence and
viral latency. These results may have therapeutic implication for viral
eradication.
TUAA0204
Epigenetic modifications of HIV proviral LTRs: potential
targets for cure
S. Weber1, H. Burger2, K. Kemal2, B. Weiser2, K. Korn1, K. Anastos3
and W. Doerfler1
1
Erlangen University, Institute for Virology, Erlangen, Germany.
2
Wadsworth Center, New York State Dept. of Health, Albany,
United States. 3Albert Einstein College of Medicine/ Montefiore
Medical Center, New York, United States
Background: HIV-1 cure remains elusive despite HAART due to the
reservoirs of proviral DNA integrated into the human genome. Efforts
to cure HIV-1 therefore need to aim at eliminating proviral DNA from
cellular reservoirs. The first epigenetic signal identified in virus
infected and uninfected cells has been promoter methylation.
Compelling evidence confirms that specific promoter methylation
can lead to gene silencing. Previous studies have examined HIV-1
epigenetics mostly in vitro.
Methods: We determined methylation patterns in HIV-1 proviral
genomes from PBMCs obtained from 21 individuals with a spectrum
of disease progression. The CpGs in the long terminal repeats (LTRs)
of proviral DNA were investigated by bisulfite sequencing in up to
85 genomic variants per individual. This approach facilitates the
study of the full range of CpG methylation and sequence variability
of HIV-1 proviruses under conditions of natural selection in human
populations.
Results: In patients with advanced disease, the HIV-1 proviruses
remained essentially unmethylated in their LTRs. In one long-term
nonprogressor, the percentage of methylated proviruses varied
from 077% at different times after infection. More important and
unexpected was the detection of three specific LTR-located CpG
dinucleotides that had been selectively mutated to TpAs in 20 out
of the 32 samples analyzed. Comparison to 11 HIV-1 LTR sequences
in the Los Alamos HIV database demonstrated that mutations in
the sites identified by our study occurred more frequently than
at other locations, although the mutations were different from
TpAs.
Conclusion: These specific CpGs, possibly including their abutting
sequences, might indicate weak spots in the proviral genomes whose
sacrifice by mutation to TpAs could enhance the HIV-1 potential for
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
long-term proviral survival. These data suggest that the sites of the
mutated CpGs occurring at conserved sites may serve as potential
targets for therapeutic interventions to eliminate integrated
proviruses.
Grants: DFG-DO165/28-1; NIH-UO1-AI35004
TUAA0205
Unique integration patterns: in vitro model of HIV latency
S. Saleh1,2, D. Vatakis3, P. Cameron1,2,4, A. Harman5, A. Cunningham5
and S. Lewin1,2,4
1
Monash University, Medicine, Melbourne, Australia. 2Burnet
Institute, Melbourne, Australia. 3University of California at Los
Angeles, Medicine, Los Angeles, United States. 4Infectious Diseases
Unit, Alfred Hospital, Melbourne, Australia. 5Westmead Millenium
Institute, Sydney, Australia
Presenting author email: suha.saleh@med.monash.edu.au
Background: We have demonstrated that HIV latency can be
established in resting CD4 T-cells infected after incubation with
the CCR7 ligand, CCL19. The aim of this study was to identify the sites
of viral integration in this model and to determine the relationship of
integration sites to transcription factor binding sites and cellular
gene expression.
Methods: Resting CD4 T-cells were incubated with either IL2/PHA,
CCL19, or in media alone (unactivated). After 2 days, cells were
infected with NL4.3 and the presence of integrated DNA was
confirmed at day 4. Total cellular DNA was purified and provirushost junctions cloned and sequenced and mapped on the human
genome using the UCSC Genome Browser. Gene expression in each
cell type was determined using Illumina microarrays. Comparisons
were made between these in vitro conditions and CD4 T-cells from
HIV-infected patients on antiretroviral therapy (ART). Gene ontology
was analysed using ClueGo.
Results: We identified unique integration sites in infected CCL19treated (n 247), IL2/PHA (n 432) and unactivated (n 133) Tcells. Integration occurred in transcriptionally active genes and most
were involved in cellular housekeeping and cell signalling pathways.
Integration sites were a similar distance from CpG islands, CTCF, pol II
and histone methylation and acetylation sites. Compared to IL2/PHAactivated and unactivated cells, integration in CCL19-treated cells
was further away from regions with high transcriptional activity
(including transcriptional start sites (TSS); (pB 0.0001)) and closer to
Long Interspersed Nuclear Elements (p B 0.0001), H4K20me3 (pB
0.0001) (a methylation site mapped to heterochromatin) and
H4R3me2 (pB 0.0001; involved in priming gene expression).
CCL19 treated cells and patient derived cells were similar in some
but not all integration site patterns.
Conclusion: HIV integration occurred in transcriptionally active genes
in all culture conditions although integration patterns in CCL19treated latently infected cells were distinct. The significance of
unique integration site selection in the setting of latency warrant
further investigation.
THAA0104
SIVagm infection of rhesus macaques: a model of functional
cure with persistent reservoirs of replication-competent
virus
D. Ma1, A. Cillo2, C.L. Xu1, J. Kristoff1, J. Fang1, G. Haret-Richter1,
J. Mellors2, I. Pandrea1 and C. Apetrei1
1
University of Pittsburgh, Center for Vaccine Research, Pittsburgh,
United States. 2University of Pittsburgh, Division of Infectious
Track A Basic Science
Diseases, Department of Medicine, Pittsburgh, United States
Presenting author email: apetreic@pitt.edu
Background: SIVagm infection of rhesus macaques (RMs) provides a
model of functional cure: initial high level viremia (108 copies/ml)
and massive mucosal CD4 T cell depletion are followed by durable
control of SIVagm replication, complete recovery of CD4 T cells,
normalization of T-cell activation and seroreversion. The advantage of
this model is that the functional cure occurs in all SIVagm-infected
RMs. Immune control of SIVagm replication can be temporary
reversed by experimental CD8-cell depletion.
Methods: Our objectives were to further characterize the RM/
SIVagm model of functional cure by: (i) assessing the level of
persistent chronic SIVagm viremia using qPCR with single copy
sensitivity (SCA); (ii) determining whether rebounding virus after
CD8-cell depletion is replication-competent by inoculation of uninfected RMs; and (iii) characterizing the diversity of rebounding virus
using single genome sequencing (SGS).
Results: SCA revealed low level viremia, averaging 20 copies/ml
(range 1030), in RMs 9 month after viremia became undetectable
by conventional qPCR. Inoculation of new RMs with plasma collected
during virus rebound after CD8 cell depletion resulted in peak
viremia of 108 109 SIVagm RNA copies/ml, followed by control of
viremia with kinetics similar to that following infection with high titer
SIVagm stock virus. SGS of rebound plasma virus after CD8 cell
depletion revealed sequence homogeneity consistent with clonality.
Rebound virus was genetically similar to unpassaged SIVagm used to
infect RMs, suggesting that the viral reservoirs that were the source
of the rebounding virus were seeded early after infection.
Conclusion: These findings further validate SIVagm-infected RMs as a
model of functional cure of replication-competent retrovirus infection. Deciphering the mechanisms of control may identify new
strategies to achieve functional cure. This model is well suited to
assess new therapeutic strategies to deplete viral reservoirs without
the complexity of multidrug antiretroviral therapy.
MOLBA01
Unintegrated HIV-1 generates an inducible reservoir of
replication competent virus in nonproliferating CD4 T cells
B. Trinité, E. Ohlson, S. Rana, J. Alster and D.N. Levy
New York University College of Dentistry, Basic Science, New York,
United States
Background: Integration into host cell chromosomal DNA is considered an essential step in the replication of retroviruses, yet HIV-1
replication in vivo or in vitro generates one to two orders of
magnitude more copies of unintegrated viral DNA (uDNA) than
successfully integrated proviruses (iDNA). These extrachromosomal
species are reported to possess limited capacity for gene expression
and to be a replicative dead end. Resting CD4 cells are the major
targets of early infection following mucosal transmission, and resting
memory CD4 T cells constitute the major reservoir of latent
infection. The cytokine environment in mucosal and lymphoid
compartments facilitates HIV-1 infection of CD4 T cells in the
absence of TCR mediated activation.
Methods: We employed a combination of HIV-1 reporter viruses,
flow cytometry and quantitative PCR to analyze HIV-1 early and late
gene expression and virus production in purified peripheral blood
CD4 T cells.
Results: We find that resting CD4 T cells rendered permissive
to HIV-1 replication by cytokines IL-2, IL-4, IL-7 or IL-15 provide a
reservoir for the persistence of unintegrated HIV-1 DNA. Nonproliferating cells containing uDNA could generate de novo HIV-1 and transmit virus efficiently to uninfected cells, resulting in recombination
14
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
between viruses. uDNA generated an order of magnitude less virus
than integrated proviruses, but cells generating virus from uDNA
survived and produced virus longer. Vpr packaged in virions was
necessary for initial gene expression from uDNA. Subsequent T cell
receptor/coreceptor-mediated activation substantially increased
early viral gene expression from uDNA, but an increase in virus
production was observed only when activation-induced cell proliferation was inhibited by de novo Vpr generated from the uDNA template.
Activation through the T cell receptor or HDAC inhibitors in
combination with Prostratin efficiently activated latent uDNA several
weeks after infection of resting T cells.
Conclusion: We propose unintegrated HIV-1 as a potential reservoir
of inducible virus.
WEPDA0202
Role of UHRF1 in transcriptional regulation and
maintenance of HIV-1 latency
A.F.B. Victoriano, Y. Hibi, N. Tan Gana, K. Asamitsu and T. Okamoto
Nagoya City University Graduate School for Medical Sciences,
Department of Molecular and Cellular Biology, Nagoya, Japan
Presenting author email: rency@med.nagoya-cu.ac.jp
Background: A thorough understanding of the molecular mechanisms governing HIV-1 latency is essential in the development of
rational therapeutics for the eradication of the virus. Evidence is
accumulating that histone methylation regulates HIV latency. The
multi-domain protein UHRF1 (ubiquitin-like, containing PHD and
RING finger domains 1), a key epigenetic regulator for maintaining
DNA methylation patterns, has also been reported to interact with
histone 3 lysine 9 methylated histones. This study investigates the
role of UHRF1 in the transcriptional silencing of latent HIV-1 provirus.
Methods: 293T cells were co-transfected with wild type HIV-1 long
terminal repeat (LTR) and either with constructs encoding wild type
or mutant forms of human UHRF1, treated with tumor necrosis
factor alpha (TNF-a) and the promoter activity was determined by
the dual luciferase assay. The presence of UHRF1 at the LTR was
assessed by chromatin immunoprecipitation assay using sheared
chromatin lysates from latently infected cells, ACH-2 and J-Lat 6.3.
Small interfering RNA (siRNA) experiments were conducted using
TZM-bl cells, which contain a chromatin-integrated HIV-1 LTR, to
confirm the influence of UHRF1 on the HIV-1 LTR.
Results: We observed that UHRF1 inhibited both basal and the
induced HIV-1 gene expression by TNF-a. Chromatin immunoprecipitation assay revealed the presence of UHRF1 at the vicinity of the
HIV-1 LTR and UHRF1 occupancy was reduced upon activation.
Meanwhile, knockdown of UHRF1 expression modestly increased
basal LTR activity.
Conclusion: Results suggest that UHRF1 contributes to the transcriptional silencing of latent HIV-1 provirus and further elucidate the
underlying molecular mechanisms that maintain latency.
WEPDA0203
Modeling HIV latency using the humanized BLT mouse
M. Marsden, M. Kovochich, N. Suree, S. Shimizu, R. Mehta,
R. Cortado, G. Bristol, D.S. An and J. Zack
UCLA, Los Angeles, United States
Presenting author email: mmarsden@ucla.edu
Background: Replication-competent HIV persists in patients who are
treated with highly active antiretroviral therapy (HAART). One
significant reservoir of this persistent virus is within rare latently
infected CD4 T cells. However, the infrequent nature of these cells
Track A Basic Science
makes them challenging to study directly in infected patients, and
clinical attempts to completely eliminate this viral reservoir have not
been successful. Therefore improved models for HIV latency and
eradication strategies are needed. The humanized bone marrow-liverthymus (BLT) mouse provides robust multi-lineage immune reconstitution with human cells. When infected with HIV, these mice can also
serve as an in vivo model for investigating HIV latency.
Methods: BLT mice were infected with HIV and assessed for the
presence of latently-infected cells. Cells were stimulated ex vivo with
a variety of canonical and novel latency activators. Infected mice
were also treated with HAART and then assessed for the presence of
activation-inducible virus.
Results: Up to 3% percent of human cells in spleen, peripheral blood,
and thymus/liver implants in HIV-infected BLT mice harbored latent
HIV. This virus was integrated, activation-inducible, and replication
competent. The latently-infected cells were also responsive to
stimulation with protein kinase C activators and latency-activating
nanoparticles. Furthermore, activation-inducible virus was detectable in HAART-treated mice, although at lower frequencies than in
untreated mice.
Conclusion: The humanized BLT mouse provides a versatile system
for ex vivo and in vivo investigation of HIV latency.
WEPDA0204
Maraviroc (MVC) can activate NFkB in resting CD4 T cells of
patients infected with R5 or D/M HIV-1
N. Madrid-Elena, B. Hernandez-Novoa, M. Lamas, L. Garcia-Bermejo
and S. Moreno
Hospital Ramon y Cajal, Madrid, Spain
Presenting author email: nadiapatricia.madrid@salud.madrid.org
Background: In a previous ART intensification study with MVC we
detected episomal 2-LTR-DNA in all patients at week 24, while
undetectable at baseline (Gutierrez C, et al. PLoS ONE, 2011). A
residual agonistic effect of MVC on CCR5 receptor through calcium
flux has been discarded. Activation of CCR5 intracellular signaling
pathways leading to transcription factors activation, including NFkB,
could promote HIV-1 transcription in resting CD4 T cells. We aimed to
study if MVC could trigger this effect.
Methods: TROPISMVC (NCT01060618) is a clinical trial of 10 days
MVC monotherapy in naı̈ve HIV-1-infected patients. Blood samples
were drawn at baseline, after 10 days of MVC and 18 days after MVC
withdrawal (day 28). PBMCs were isolated from nine patients,
bearing CCR5 (n 6) and D/M (n 3) tropic viruses. Resting CD4 T
†
cells were separated by MACS Technology and aliquots of 5 million
cells were frozen. Nuclear proteins were obtained using the Actif
Motif Nuclear Extract Kit. NFkB activation was detected by ELISA
plates coated with oligonucleotides mimicking the specific consensus
binding sites (TransAMTM NFkB family, Actif Motif), following
the manufacturer’s instructions. NFkB activity was estimated measuring target genes’ expression by real-time PCR of the extracted
RNA.
Results: NFkB activity was detected in 4/6 patients with R5 tropic
viruses and in 2/3 patients with D/M tropic viruses; results expressed
in fold change (FC) compared to baseline according to HIV-1 tropism.
The presence of MVC increased NFkB activity consistently, as
summarized in the following table. Upregulation of at least one
NFkB targeted gene was observed in all but one cases with available
RNA sample.
Conclusion: MVC can activate NFkB, and the expression of targeted
genes, in resting CD4 T cells from HIV-infected patients regardless of
the viral tropism. Through this pathway, MVC could trigger HIV-1
transcription in resting cells thus accelerating the decay of the HIV-1
cell reservoir.
15
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track A Basic Science
Resting CD4 Tcell
NF-kB(FC)
IFN-g(FC)
Day 10
(on MVC)
Day 28
(off MVC)
Day 10
(on MVC)
27 (R5)
7.6
10.4
28 (R5)
4.6
5.3
35 (RS)
4.6
29 (R5)
17.6
50 (D/W)
57 (D/M)
Pattern (Tropism)
IL-6, (FC)
Day 28
(off MVC)
Day 10
(on MVC)
226
164
B2
B2
B2
10.1
NA
9.1
10.5
B2
2.6
10.8
MA
B2
IL-10 (FC)
TNF-a(FC)
Day 28
(on MVC)
Day 10
(on MVC)
Day 28
(off MVC)
21.4
5
221
B2
B2
B2
2
B2
4.2
NA
NA
11.2
MA
Day 10
(on MVC)
Day 28
(on MVC)
103.8
41
195
B2
B2
B2
B2
3.1
B2
B2
NA
NA
NA
NA
NA
4.1
4.1
B2
B2
25.3
B2
B2
B2
NA
MA
446.7
38.8
NFkB activity.
THPDA0205
CXCR4-tropism is associated with the preferential
establishment of an HIV-reservoir in naı̈ve CD4 T cells
among HIV-positive Ugandan children receiving
antiretroviral therapy
T. Ruel1, J. Achan2, W. Huang3, H. Cao4, P. Li4, L.A. Eller5, M. Killian4,
E. Sinclair4, E. Charlebois4, D.V. Havlir4 and J. Wong4
1
University of Calfornia at San Francisco, Department of Pediatrics,
San Francisco, United States. 2Makerere University College of Health
Sciences, Department of Paediatrics, Kampala, Uganda. 3Monogram
Biosciences, South San Francisco, United States. 4University of
Calfornia at San Francisco, Department of Medicine, San Francisco,
United States. 5US Military HIV Research Program, Bethesda,
United States
Presenting author email: ruelt@peds.ucsf.edu
Background: Children have large populations of naive CD4 T-cells
that characteristically express high levels of CXCR4 and low levels of
CCR5, compared to memory CD4 T-cells. We hypothesized that
HIV Ugandan children infected with CXCR4-tropic virus would
exhibit larger HIV-DNA reservoirs in naı̈ve CD4 T-cells, compared to
children infected with CCR5-tropic (R5) virus.
Methods: Cryopreserved PBMC from a convenience sample of 12
HIV Ugandan children receiving antiretroviral therapy (ART) with
undetectable plasma HIV-RNA ( B 400 copies/ml, Amplicor, Roche)
were sorted into naı̈ve (CD27CD45RA) and memory (CD27CD45 and CD45-CD279) CD3CD4 T-cells. HIV-DNA levels
were determined using a Taqman assay targeting gag, normalized to
cellular-DNA content (tert, ABI). Co-receptor tropism was determined
using a commercial phenotypic assay (Trophile, Monogram). We
calculated 1) the ratio of the prevalence of infection (copies per 106
cells) in naı̈ve to the prevalence in memory CD4 T-cells and 2) the
proportion of the total peripheral CD4 T-cell HIV-reservoir that is
contained in naı̈ve CD4 T-cells, and compared them between
children with R5- and dual/mixed(CXCR4/CCR5, DM)-tropic virus
using non-parametric statistics.
Results: Median age was 4.9 (interquartile range 3.5-8.1) years,
CD4T-cell number 743 cells/ul (565-1089), CD4 T-cell percentage
25 (21-29), and ART duration 95 days (95-147), with 6 subjects each
with HIV-envelope-subtypes A and D. R5 virus was identified in 8 and
DM virus in 4 children.
Conclusion: In ART-treated adults, the vast majority of persistently
infected CD4 T-cells are memory cells. By contrast, we found that a
significant proportion of the reservoir resides in the naı̈ve CD4 Tcells among Ugandan HIV ART-treated children. Infection with DM
virus was associated with preferential naı̈ve T-cell infection. In
developing strategies to eradicate HIV, it will be important to take
into account the high levels of naı̈ve T-cell infection in children,
particularly among those with DM virus.
A28 - Mechanisms of eradication
THAA0101
Long-term reduction in peripheral blood HIV-1 reservoirs
following reduced-intensity conditioning allogeneic stem
cell transplantation in two HIV-positive individuals
T.J. Henrich1,2, G. Sciaranghella3, J.Z. Li1,2, S. Gallien4, V. Ho2,5,
A.S. Lacasce2,5 and D.R. Kuritzkes1,2
1
Brigham and Women’s Hospital, Boston, United States. 2Harvard
Medical School, Boston, United States. 3Ragon Institute of MGH, MIT
and Harvard, Boston, United States. 4Hopital Saint-Louis, Paris,
France. 5Dana-Farber Cancer Institute, Boston, United States
Presenting author email: thenrich@partners.org
Background: Functional HIV-1 cure has been described in the setting
of myeloablative allogeneic stem cell transplant (alloSCT) with
ccr5^32/ ccr5^32 donor cells, but the effects of alloSCT on viral
reservoirs are largely unknown. We studied the longitudinal effects
HIV Copies/10^6
HIV Copies/10^6 Memory
Ratio of infection
HIVNaive CD4T-cells/Total
Naı̈ve CD4T-Cells
CD4T-cells
prevalence
HIVCD4T-cells
R5
2,962 (12910,668)
9,931 (103711,808)
0.7 (0.24.3)
53% (25%80%)
DM
14,733 (1,344135,120)
930 (15129,702)
8.9 (6.613.0)
92% (88%95%)
P-value*
0.31
0.61
0.04
0.07
* Comparing R5 to DM with Kruskal-Wallis Test.
HIV-Reservoir by CCR5/DM Tropism.
16
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track A Basic Science
MD, United States. 3Merck Research Laboratories, West Point, PA
United States
Presenting author email: lifsonj@mail.nih.gov
of reduced-intensity conditioning (RIC) alloSCT on HIV-1 peripheral
blood reservoirs in two infected male patients with hematologic
malignancies who previously underwent autologous SCT.
Methods: Analysis of peripheral HIV-1 reservoirs was performed on
banked samples (1 pre- and 3 post-RIC-AlloSCT) for both patients,
including: 1) quantification of HIV-1 DNA from peripheral blood
mononuclear cells (PBMCs), 2) quantification of 2-LTR circles from
PBMC episomal DNA, 3) full-length envelope amplification and
phenotypic coreceptor usage prediction from proviral DNA, 4)
quantification of plasma viremia by a single-copy assay, 5) flow
cytometric characterization of lymphocyte subsets and coreceptor
expression, and 6) CCR5 genotyping.
Results: No HIV-1 DNA was detected 8 to 17 months after alloSCT
in PBMC from both patients despite presence of modest levels of
total PBMC-associated HIV-1 DNA prior to and 2-3 months after
SCT (87271 copies/106 PBMCs). 2-LTR circles were not detected
at any time-point despite excellent recovery of episomal mitochondrial DNA. Both patients were heterozygous for ccr5^32
mutation prior to transplant; a transient reduction in CXCR4
expression was observed following transplant. Pseudoviruses
incorporating envelopes from early time-points used predominately CCR5 for entry. Both patients remained virologically
suppressed on ART, but were either started on prednisone or
continued on tacrolimus/sirolimus immunosuppressive therapy for
chronic graft-versus-host disease (GVHD) near the time of loss of
HIV-1 reservoir detection.
Conclusion: PBMC HIV-1 DNA became undetectable 8 months after
RIC-alloSCT. This finding may be due to a dilutional effect of donor
cell engraftment in the setting of protective ART, the additive effect
of cytotoxic therapies, and/or GVHD. Confirmation of results by
sampling large-volume blood collections and other tissue compartments is warranted.
Background: Nonhuman primate (NHP) models are needed for
evaluation of proposed but unproven, and potentially dangerous
strategies targeting residual virus and latent reservoirs in AIDS virusinfected subjects receiving suppressive antiretroviral drug treatment (ART), but such models have proven challenging to develop.
Methods: We treated a cohort of 6 Indian rhesus macaques with
a novel three class (NRTI, PI, IN-STI) six drug (PMPA/FTC/DRV-RTV/
L-870812/L-870564) ART regimen beginning at 4 weeks postinfection with SIVmac239. Peripheral blood CD4 T cells from ARTtreated animals with suppressed viremia were evaluated ex vivo
for responses to SAHA, including changes in histone acetylation
patterns and induction of expression of SIV. Beginning approximately
26 weeks post infection, animals received four 21 day courses of
daily treatment with SAHA, with each course of SAHA separated by
an approximately 3 week interval, with continuous ART throughout
and longitudinal sampling of blood and lymph nodes for immunological, virological, and pharmacodynamic evaluations. Animals were
euthanized and necropsied after the final SAHA dose, while still on
ART, and tissues studied virologically.
Results: The ART regimen was feasible, safe and well tolerated
over one year of treatment and allowed suppression of plasma
viremia to B30 copy Eq/mL. Ex vivo SAHA treatment of CD4 T cells
from ART-suppressed macaques increased histone acetylation and
induced SIV expression. SAHA treatment of macaques was safe and
well tolerated, and induced measurable in vivo changes in histone
acetylation in CD4 T cells but did not reproducibly impact plasma
viremia. Analysis of cell associated viral DNA and RNA levels from
blood and tissues is in progress and will be presented.
Conclusion: This study demonstrates the feasibility of developing
and applying NHP models for studying AIDS virus reservoirs and
eradication strategies, along with the in vivo safety of SAHA treatment at pharmacologically active doses.
MOLBA02
Evaluation of treatment with the histone deacetylase
inhibitor vorinostat (suberoylanilide hydroxamic acid;
SAHA) in antiretroviral drug treated, SIVmac239-infected
rhesus macaques
1
1
1
1
THPDA0201
The cure of the ’Berlin patient’: why did pre-existing X4variants not emergence after allogeneic CCR5-D32 SCT?
2
J. Lifson , G. Del Prete , R. Kiser , C.M. Trubey , J. Smedley ,
V. Coalter1, K. Oswald1, R. Shoemaker1, R. Fast1, Y. Li1, A. Lara1,
A. Wiles1, R. Wiles1, R. Macallister2, R. Sanchez3, J. Wai3, C. Tan3,
B. Keele1, J. Estes1, M. Piatakjr1 and D. Hazuda3
1
SAIC Frederick, Inc., Frederick Naitonal Laboratory for Cancer
Research, AIDS and Cancer Virus Program, Frederick, MD,
United States. 2SAIC-Frederick, Inc., Frederick National Laboratory for
Cancer Research, Laboratory Animal Sciences Program, Frederick,
J. Symons1, S. Deeks2, G. Hutter3, A. Wensing1, J. Martin2, P. van
Ham1, L. Vandekerckhove4 and M. Nijhuis1
1
University Medical Center Utrecht, Department of Virology, Utrecht,
Netherlands. 2University of California, Department of Medicine
San Francisco, United States. 3Heidelberg University, Institute of
Transfusion Medicine and Immunology, Mannheim, Germany
Sample Collection Time
Total HIV-1 DNA
2-LTR HIV-1 DNA
Plasma HIV-1 RNA
(months from allogeneic SCT)
(copies/million PBMCs)
(copies/million PBMCs)
(copies/ml)
A
0.5 (pre-SCT)
144
ND
B3
A
2
87
ND
B3
Patient
A
8
ND
ND
B3
A
B
14
0.2 (pre-SCT)
ND
96
ND
ND
B3
B3
B
3
281
ND
B3
B
9
ND
ND
B3
B
17
ND
ND
B3
ND Target Not Detected
Quantification of Peripheral Blood HIV Reservoirs.
17
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
.4Ghent University Hospital, Department of Internal Medicine,
Infectious Diseases and Phychosomatic Medicine, Ghent, Belgium
Presenting author email: j.symons@umcutrecht.nl
Background: The ‘‘Berlin patient’’ is the first patient functionally
cured of HIV. He received stem cell transplantation from a
homozygote CCR5-D32 donor. The reconstituted CD4 T-cell population should be susceptible to infection with CXCR4-using viruses.
According to gp120-V3 deep sequencing analysis of plasma-derived
variants present before transplantation, the patient harbored a
minority (2.9%) of viruses predicted to be CXCR4-tropic (geno2phenocoreceptor FPR 10%). It remains puzzling why these variants failed to
emerge post-transplant. We hypothesize that these CXCR4-predicted
variants depend on CCR5 for replication.
Methods: Patient-derived viral constructs were generated by cloning
V3-sequences of the CXCR4-predicted viruses (pX1-pX7) and the
dominant CCR5-predicted strain (pR5) into HXB2-DV3. As controls
V3-sequences of HXB2 (cHXB2; CXCR4-tropic) and BaL (cBaL; CCR5tropic) were cloned. Co-receptor preference was investigated in U373-MAGI-cells expressing CD4CCR5 or CD4CXCR4, PBMCs
from healthy donors and patient-derived post-transplant CCR5-D32
PBMCs.
Results: Three pre-transplant CXCR4-predicted strains had an amino
acid substitution in the V3 glycosylation-motif and one had a lysine
at position 25, all associated with CXCR4-tropism. Five of the 7 viral
clones were infectious. As expected cHXB2 infected CD4CXCR4MAGI-cells and was inhibited by AMD-3100 (CXCR4-inhibitor) in
donor PBMCs. Remarkably, the CXCR4-predicted viruses (FPR 2.7
9.3) depended on CCR5 for replication in MAGI-cells and were
inhibited by maraviroc (CCR5-inhibitor) in donor PBMCs similar to
pR5 and cBaL. As an ultimate proof it was shown that CXCR4predicted strains could not replicate in the post-transplant derived
CCR5-D32 PBMCs, whereas cHXB2 replication was observed.
Conclusion: The minority population of CXCR4-predicted viral strains
which the patient harbored pre-transplant were fully dependent on
CCR5 for replication in vitro. This could explain lack of rebound after
treatment discontinuation. This provides a strong rationale for the
further development of CCR5-targeted gene therapy and suggests
that successful reconstitution of CCR5-depleted immune system may
work, even if there is some evidence of CXCR4-predicted variants.
A29 - Tissue reservoirs
THAA0102
Viral tissue reservoirs are determined early and little viral
RNA is detected during suppression by three or four drug
regimens in the macaque model
C. Kline1, J. Ndjomou1, T. Franks1, R. Kiser2, V. Coalter2, M. Piatak, Jr2,
J. Estes2, J. Mellors1, J. Lifson2 and Z. Ambrose1
1
University of Pittsburgh School of Medicine, Medicine, Pittsburgh,
United States. 2SAIC-Frederick, Inc., NCI Frederick, AIDS and Cancer
Virus Program, Frederick, United States
Presenting author email: zaa4@pitt.edu
Background: Although HIV-infected individuals can suppress plasma
viremia to undetectable levels with antiretroviral therapy, infected
cells remain in the body and can contribute to viremia when therapy
is discontinued. Macaque models allow investigators to more easily
characterize viral reservoirs.
Methods: Twelve male macaques were infected with RT-SHIV, an SIV
virus containing HIV-1 reverse transcriptase, and monitored for
plasma viremia and CD4 counts. After 10-14 weeks post-infection,
Track A Basic Science
6 animals were not treated and 6 animals were treated for 1720
weeks with 3 drugs (tenofovir, lamivudine, and efavirenz) or 4 drugs
(tenofovir, lamivudine, efavirenz, and an integrase inhibitor). Viral
RNA and viral DNA were measured longitudinally in the blood and
at necropsy in over 20 different tissues by quantitative PCR and
normalized for cellular RNA and DNA.
Results: In untreated and treated animals, RT-SHIV DNA was highest
in lymphoid and gastrointestinal tissues and very low to absent in the
brain, genital tract, and kidney. The amount of viral DNA detected in
multiple lymphoid tissues correlated with the level of plasma viremia
1 week post-infection. RT-SHIV RNA was abundant in the lymphoid
tissues of untreated macaques with detectable viremia, but was
detected variably in different regions of the gastrointestinal tract.
Little or no viral RNA was detected in the tissues from animals after
17-20 weeks of therapy. There was no obvious difference in RT-SHIV
RNA levels between animals treated with 3 or 4 drugs.
Conclusion: Our results suggest that the majority of virally-infected
cells are located in lymphoid tissues with variable levels in the
gastrointestinal tract. The number of infected cells in these reservoirs
correlates with viremia one week after infection, suggesting that viral
reservoirs are seeded within days of infection. Little viral RNA is
evident in tissue after suppressive therapy with either 3 or 4
antiretroviral drugs.
THAA0105
Characterization of persistent HIV-1 in a broad spectrum of
CD4 T cells isolated from peripheral blood and gut
associated lymphoid tissue from patients on long-term
suppressive therapy
L. Josefsson1,2, S. Eriksson2, E. Sinclair3, T. Ho3, M. Killian3, L. Epling3,
A. Tan3, P. Lemey4, N.R. Faria4, W. Shao5, P. Hunt3, M. Somsouk3,
D. Douek6, P. Bacchetti7, L. Loeb3, J. Custer3, L. Poole3, S. Deeks3,
F.M. Hecht3 and S. Palmer1,2
1
Karolinska Institutet, Department of Microbiology, Tumor and
Cellbiology, Solna, Sweden. 2The Swedish Institute for Communicable
Disease Control, Department of Diagnostics and Vaccinology, Solna,
Sweden. 3University of California - San Francisco, Department of
Medicine, San Francisco, United States. 4KU Leuven, Rega Institute,
Leuven, Belgium. 5National Institiute of Cancer, Advanced Biomedical
Computing Center, SAIC, Frederick, United States. 6National Institute
of Allergy and Infectious Diseases, National Institutes of Health,
Immunology Laboratory, Vaccine Research Center, Bethesda,
United States. 7University of California - San Francisco, Department
of Epidemiology and Biostatistics, San Francisco, United States
Presenting author email: lina.josefsson@smi.se
Background: The role of ongoing virus replication in HIV persistence
during long-term antiretroviral therapy is unknown. Since residual
replication should result in detectable evolution, we investigated the
degree of sequence evolution in blood-derived and rectal tissuederived CD4 T cells.
Methods: Using single-genome and single-proviral sequencing techniques, we obtained 20-50 single viral genomes from pre-therapy
plasma samples from 5 subjects who initiated therapy during
acute infection and 3 subjects who initiated therapy during chronic
infection. Pre-therapy plasma viral sequences were compared to
single proviral HIV-1 genomes derived from HIV-1-infected T-cells
(naı̈ve, memory, central- and effector-memory) from peripheral
blood (PB) and gut-associated lymphoid tissue (GALT) samples
collected after 4-12 years of suppressive therapy. Maximum likelihood
phylogenetic trees were constructed using the general time reversible
model incorporating rate variation among sites. Evolutionary divergence was explored using root-to-tip analysis (Path-O-Gen).
18
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Results: The geometric mean infection frequency of memory
and naı̈ve CD4 T-cells in the PB was 13- and 24-fold higher
respectively in subjects treated during chronic compared to acute
infection. This was also true for effector memory CD4 T-cells from
the GALT (6-fold higher). Phylogenetic analysis revealed clear evidence
against any substantial evolution between the pre-therapy plasmaderived HIV RNA sequences and on-therapy intracellular HIV DNA
sequences. Numerous intracellular HIV sequences identified after
long-term therapy contained replication-incompetent virus. One
patient had a predominant intracellular clone in both memory and
effector memory T-cells containing a 380bp deletion after 9 years of
therapy.
Conclusion: Early initiation of effective therapy results in substantially lower reservoir size in blood and gut. The lack of HIV-1 genetic
evolution in the HIV-1 infected CD4 T-cell populations after years
of therapy argues against virus replication as a major cause of
persistence in these cell populations. The role of replication in other
tissues and cell types however remains to be defined.
Track A Basic Science
polymorphisms (away from consensus B) that could explain reduced
anti-APOBEC3G activity of Vif derived from EC.
Conclusion: Anti-APOBEC3G activity of Vif proteins derived from EC
was reduced. This reduced activity was independent of presence or
absence of known protective HLA alleles. Common Vif mutations in
EC unlikely explain the observed reduction; rather it might be
attributable to unique mutations to each EC Vif protein.
TUAA0203
CBF-1 induces both establishment and maintenance of HIV
latency via recruiting PcG corepressor complex at LTR
M. Tyagi
George Mason University, Manassas, United States
Presenting author email: mudittyagi1970@gmail.com
T. Kikuchi1, Y. Iwabu2, A. Kawana-Tachikawa1, M. Koga1, N. Hosoya1,
S. Nomura1, Z.L. Brumme3, H. Jessen4, A. Kelleher5, M. Markowitz6,
F. Pereyra7, A. Trocha7, B.D. Walker7, A. Iwamoto1, K. Tokunaga2 and
T. Miura8
1
The Institute of Medical Science, the University of Tokyo, Tokyo,
Japan. 2National Institute of Infectious Diseases, Tokyo, Japan.
3
Simon Fraser University, Burnaby, Canada. 4Jessen Praxis, Berilin,
Germany. 5University of New South Wales, Sydney, Australia. 6Aaron
Diamond AIDS Research Center, New York, United States. 7MIT and
Harvard, Ragon Institute of MGH, Charlestown, United States.
8
Nagasaki University, Nagasaki, Japan
Background: Repressive epigenetic modifications have been shown
to induce and maintain HIV latency; however underlying molecular
mechanisms are not yet clear. We have previously demonstrated the
critical role of CBF-1 (Latency-C-promoter binding factor 1) in
establishing repressive chromatin structures at HIV LTR during
latency establishment. The knockdown of CBF-1 results in the
reactivation of latent proviruses and overexpression of CBF-1
facilitates latency establishment. Here we extend these studies to
show that multiple repressive epigenetic modifications that CBF-1
induces are the result of recruitment of Polycomb Group (PcG)
corepressor complex at HIV LTR by CBF-1.
Methods: Both transformed and primary T cells were infected with
lentiviral vectors expressing Tat in cis to study the underlying
molecular mechanisms regulating HIV latency and via running
various molecular assays, including Chromatin Immunoprecipitation
(ChIP) assays.
Results: In this study, we demonstrate that CBF-1 induces repressive
chromatin structures at HIV LTR by recruiting Polycomb Group (PcG)
corepressor complex at HIV LTR. The knockdown of endogenous CBF1 results in the dissociation of PcG complex components from HIV
LTR. Furthermore, knockdown of the individual components of PcG
complex leads to the reactivation of latent HIV proviruses demonstrating the direct role of PcG complex in establishing HIV latency.
Overall our results demonstrate that the CBF-1 induced various
Background: HIV-1-infected individuals who control viremia to below
the limit of detection without antiviral therapy have been termed
elite controllers (EC). Functional attenuation of some HIV-1 proteins
has been reported in EC. However, little is known about role of the
HIV-1 accessory protein Vif function in EC, which enhances HIV-1
infectivity through APOBEC3G degradation. In this study, the antiAPOBEC3G function of Vif was compared between EC, chronic
progressors (CP) and individuals with acute infection (AI).
Methods: Forty-nine EC, 49 CP and 44 AI were studied. vif genes
were amplified by nested RT-PCR using concentrated plasma. To
compare anti-APOBEC3G activity of Vif proteins among those groups,
VSV-G-pseudotyped viruses were generated by co-transfecting 293T
cells with expression plasmids encoding patient-derived Vif,
APOBEC3G, VSV-G, together with a vif/env-deficient HIV-1 proviral
DNA clone carrying a luciferase reporter gene. VSV-G-pseudotyped
viruses were normalized for p24 antigen and used to infect 293T cells
and luciferase activity was measured at 48 h postinfection.
Results: Anti-APOBEC3G activity of Vif from EC was significantly
reduced compared to those from CP or AI (Figure 1). These results
remained significant after excluding individuals expressing protective
HLA alleles B*27 and/or B*57. No significant difference was observed
between CP and AI. Significant differences in amino acid usage in vif
genes were found at 7 residues between CP and EC, and at 13
residues between AI and EC. However, there were no common
Figure 1. Comparison of anti-APOBEC3G activity of Vif From AI, CP
and EC patients.
Each dot represents mean RLU of each patient.
A30 - Host cellular factors and latency
TUAA0103
Anti-APOBEC3G activity of HIV-1 Vif protein from elite
controllers is attenuated compared to those from untreated
chronic progressors or those from individuals with acute
infection
19
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
epigenetic modifications are the result of recruitment of Polycomb
Group (PcG) corepressor complex at HIV LTR, which carry a variety of
epigenetic factors that repress HIV gene expression via generating
several layers of repressive epigenetic modifications.
Conclusion: We have established that analogous to the transformed
T cell lines in primary T cells CBF-1 induced repressive chromatin
structures play important role in establishing HIV latency. Additionally by recruiting PcG corepressor complex at LTR, CBF-1 not only
facilitates HIV latency establishment also play critical role in
maintaining and stabilizing the latent proviruses.
THAA0103
Distribution of the HIV reservoir in patients spontaneously
controlling HIV infection after treatment interruption
C. Bacchus1, L. Hocqueloux2, V. Avettand-Fenoël3, A. Saez-Cirion4,
A. Mélard3, B. Descours5, A. Samri1, C. Blanc6, B. Autran1,
C. Rouzioux3 and VISCONTI and ALT ANRS study groups
1
Cellular and Tissular Immunology Laboratory, Pierre and Marie Curie
UniversityPitié-Salpêtrière Hospital, INSERM UMR-S 945, Paris,
France. 2Infectious and Tropical Diseases Department, Regional
Hospital, Orléans, France. 3Virology Laboratory, René Descartes
University, Necker Hospital, Paris, France. 4Institut Pasteur, Unité de
Régulation des Infections Rétrovirales, Paris, France. 5Human Genetic
Institute, Molecular Virology Laboratory, CNRS UPR1142,
Montpellier, France. 6Flow Cytometry Platform CyPS, Pierre and
Marie Curie University, Pitié-Salpêtrière Hospital, Paris, France
Presenting author email: charlinebacchus@gmail.com
Background: Virological and Immunological Studies in CONtrollers
after Treatment Interruption (VISCONTI) are required to understand
the benefits of an early treatment at acute HIV-1 infection on the HIV
reservoir. We studied the distribution, magnitude and inducibility of
the HIV reservoir in VISCONTI patients.
Methods: The prospective VISCONTI study included twelve patients
controlling HIV for a median of 76[IQR:67.584.5] months after
interruption of a 3[IQR:1.75.9] years long HAART initiated within 10
weeks post-infection. Circulating resting CD25-CD69-HLADR- CD4T
cell subsets were sorted as naive (TN), central-memory (TCM),
transitional-memory (TTM) and effector-memory cells (TEM) for
further cell-associated HIV-DNA quantification by ultrasensitive realtime-PCR, and viral inducibility by culture with anti-CD3/anti-CD28/
IL-2/IL-7. Reservoir distribution was compared to the one observed
in 8 untreated Elite-Controllers for whom 90% of HIV-RNA measures
was undetectable (below 200 copies) over 12[914] years.
Results: In the VISCONTI group, activated CD4T cells had
significantly higher HIV-DNA levels than resting ones (median
2.7[IQR:2.43.4] and 2[IQR:1.82.5] log copies/million cells,
p0.005). HIV-DNA was detected in all subsets from all patients
except for 8 out of 12 TN-sorted cells, which were 10 fold less
infected than all memory subsets (median TN:1.5[IQR:1.21.6],
TCM:2.5[IQR:1.82.9], TTM:2.6[IQR:2.22.8] and TEM:2.4[IQR:2
2.8] log copies/million cells, pB 0.007). TTM was the major subset
contributing to 56% of this reservoir. The same HIV reservoir
characteristics were observed in Elite-Controllers in term of magnitude and distribution, except that both TCM and TTM equally
contributed to the Elite-Controllers HIV reservoir. The VISCONTI HIV
reservoir was inducible after TCR-stimulation in all sorted memory
subsets from all patients, except in TN where no virus was recovered
in 6 out of 8 patients.
Conclusion: In VISCONTI patients, treatment initiated at primary
HIV-1 infection leads, after treatment interruption, to a low -but
inducible- durable HIV reservoir distributed mainly in short-lived
Track A Basic Science
memory CD4T cells that mimicks the natural distribution observed
in Elite-Controllers.
MOPDA0105
Immune and inflammatory gene expression in the
periphery and CNS of cART-treated SIV-infected macaques
M.C. Zink, D.R. Graham, L. Gama, S.E. Queen, K.A. Meulendyke,
J.L. Mankowski and J.E. Clements
Johns Hopkins School of Medicine, Baltimore, United States
Presenting author email: mczink@jhmi.edu
Background: A major hurdle toward curing HIV is the establishment
of long-lived latent reservoirs such as the CNS. Using an SIV model of
HIV infection we examined the effect of combination antiretroviral
therapy (cART) on immune and inflammatory gene expression in the
periphery and CNS that leads to virus downregulation.
Methods: To examine the effect of cART on acute and long-term
systemic and CNS immunopathogenesis, groups of SIV-infected
macaques were untreated and euthanized at 21 postinoculation
(dpi) or end stage disease, or treated with cART starting at 4 or 12 dpi
and euthanized at 21 or 175 dpi, respectively. RNAs for immune and
inflammatory genes were quantified in the spleen and brain by nonamplification Nanostring technology or by qRT-PCR. SIV replication
and viral DNA were also measured.
Results: cART initiation at 4 or 12 dpi did not prevent SIV seeding of
the brain; brain viral DNA levels were the same as in untreated
animals. cART treatment initiated at 4 dpi had little effect on
peripheral and CNS immune and inflammatory gene expression
profiles as compared to responses mounted in untreated macaques
after acute infection, as indicated by similar levels of IL17A, IL17F,
and CCL5 in the periphery and IL-6, IFNß, and TNFa in the CNS.
Conclusion: The CNS is a latent reservoir for SIV that is seeded early
after infection regardless of cART initiation at 4 or 12 dpi. The innate
and adaptive immune responses are nearly as effective as early cART
treatment at returning the host to peripheral and CNS immune
homeostasis by 21 dpi. However, at the same time those responses
likely promote the establishment of latent reservoirs by suppressing
viral replication, not eliminating the reservoir.
A31 - Host genetics of resistance and
susceptibility
MOPDA0101
Toll-like receptor (TLR) 9 variant is associated with motherto-child transmission (MTCT) of HIV-1 and TLR9 and TLR8
variants are associated with peak viral load in HIV-1-positive
infants
K. Beima-Sofie1, A. Bigham2, J.R. Lingappa3,4,5, D. Wamalwa6,
R.D. Mackelprang7, E. Maleche-Obimbo6, B. Richardson8 and
G. John-Stewart3,4,9
1
University of Washington, Public Health Genetics, Seattle,
United States. 2University of Michigan, Anthropology, Ann Arbor,
United States. 3University of Washington, Medicine, Seattle,
United States. 4University of Washington, Global Health, Seattle,
United States. 5University of Washington, Pediatrics, Seattle,
United States. 6University of Nairobi, Nairobi, Kenya. 7University of
Washington, Seattle, United States. 8University of Washington,
20
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Biostatistics, Seattle, United States. 9University of Washington,
Epidemiology, Seattle, United States
Presenting author email: beimak@uw.edu
Background: Toll-like receptors (TLRs) are critical proteins of the
innate immune system. We evaluated association of single nucleotide polymorphisms (SNPs) in 6 TLR and 2 TLR-associated genes with
infant HIV-1 acquisition and progression.
Methods: HIV-outcomes were assessed from birth to 1-year of age
among infants from a Kenyan perinatal cohort in which HIV-infected
women were enrolled during pregnancy and received short-course
zidovudine. Infants were genotyped for 6 candidate and 118
haplotype-tagging polymorphisms in TLRs 2, 3, 4, 7, 8, and 9,
MyD88 and TIRAP, and 144 ancestral informative markers. Cox
proportional hazards and linear regression were performed to assess
TLR polymorphism associations with HIV-1 acquisition, peak HIV-1
RNA levels, and infant mortality. Sex-stratified analyses of TLR7 and
TLR8 were conducted due to their X-chromosome location.
Results: Among 368 mother-infant pairs, 56 (15%) infants acquired
HIV-1 by month 1 and 17 (4.6%) between 1 and 12 months. Infants
with the TLR9 1635A (rs352140) variant were more likely to acquire
HIV by 1 month (HR 1.49, 95% confidence interval [CI] 1.04
2.38, p0.028) and by month 12 (HR 1.40, CI 1.021.92,
p0.038) in additive models adjusted for maternal plasma HIV-1
viral load (VL) and genetic ancestry. Among 56 HIV-1 infected infants
infected at B1 month, peak VL was 6.8 log10 c/ml. The TLR9 1635A
allele was associated with a 0.40 log10 c/ml decrease in peak VL
(p 0.002); female infants with the TLR8 1G (rs3764880) variant had
a 0.62 log10 c/ml increase in peak VL (p 0.001). No variants were
significantly associated with mortality in infected infants.
Conclusion: This study is the first to evaluate the association
between TLR polymorphisms and HIV-related outcomes in a perinatal
African cohort and confirms TLR9 associations previously observed in
Caucasians. Defining the role of TLR polymorphisms in HIV-1
transmission and progression may inform future prevention strategies that exploit the innate immune response.
MOPDA0102
Polymorphisms in TLR2 and TLR7 are associated with
plasma HIV-1 RNA set-point in an African heterosexual
cohort
R. Mackelprang1, A. Bigham2, C. Celum1, G. de Bruyn3, K. Beima1,
G. John-Stewart1, A. Ronald4, N. Mugo5, A. Rainer1, K. Buckingham1,
M. Bamshad1, J. Mullins1, J. McElrath1 and J. Lingappa1
1
University of Washington, Seattle, United States. 2University of
Michigan, Ann Arbor, United States. 3University of the
Witwatersrand, Johannesburg, South Africa. 4University of Manitoba,
Winnipeg, Canada. 5University of Nairobi, Kenyatta National Hospital,
Nairobi, Kenya
Presenting author email: romelm@u.washington.edu
Background: The Toll-like receptor (TLR) genes mediate the innate
response to viral infections and may impact HIV-1 pathogenesis. We
evaluated TLR polymorphisms for association with plasma HIV-1 RNA
set-point in HIV-1 infected individuals from East and Southern Africa.
Methods: Analyses included prospective data and DNA from 500
Africans with heterosexually-acquired HIV-1 (125 incident, 375
prevalent). For incident HIV-1, set-point was defined as the median
plasma HIV-1 RNA level ]4 months after the estimated infection
date. For prevalent HIV-1, set-point was the average of ]2
consecutive plasma HIV-1 RNA measurements before ART initiation
or CD4 decline to B200 cells/mm3. Genotyping was performed for
124 single nucleotide polymorphisms (SNPs) from 6 TLR and 2 TLR-
Track A Basic Science
associated signaling genes (TIRAP and MYD88) and 144 ancestral
informative markers. These included 8 candidate SNPs previously
associated with HIV-1, and 115 haplotype tagging SNPs (tagSNPs)
representing common variation across TLR genes. Associations were
determined using linear regression with adjustment for sex, age, and
population stratification, and Bonferroni correction.
Results: Among 492 HIV-1 infected individuals who passed
quality control, the median HIV-1 set-point was 4.6 (IQR: 3.85.0)
log10 copies/mL and did not differ between seroprevalent and
seroincident participants. TLR2-rs3804100 (minor allele frequency
[MAF] 0.053), a candidate C-T synonymous SNP located in exon 1
was associated with an average 0.37 (95% confidence interval [CI]:
0.10, 0.65, p 0.007) log10 copies/ml increased set-point. TLR7rs179012, a haplotype-tagging SNP located in intron 1 was associated
with a 0.31 (95% CI: 0.47, 0.14, Bonferroni-adjusted p0.032) log10
copies/ml decrease in HIV-1 set-point.
Conclusion: These are the first associations between TLR polymorphisms and plasma HIV-1 RNA level reported among African populations.
TLR2 rs3804100 has been previously linked with more rapid disease
progression in Caucasians. Our finding of TLR7 rs179012and improved
control of infection has not been previously reported. Further study of
these SNPs may improve understanding of HIV-1 pathogenesis.
MOPDA0103
Association of polymorphisms in the regulatory region of
cyclophilin A gene (PPIA) with disease progression and gene
expression levels
P. Madlala1,2, R. Singh1, L. Werner3, S. Sibeko3, P. An4, S.S.A. Karim3,
C.A. Winkler4 and T. Ndung’u1
1
University of KwaZulu-Natal, Nelson R. Mandela School of Medicine,
HIV Pathogenesis Programme (HPP), Durban, South Africa.
2
University of KwaZulu-Natal, Genetics, Pietermaritzburg, South
Africa. 3University of KwaZulu-Natal, Nelson R. Mandela School of
Medicine, Centre for the AIDS Programme of Research in South
Africa (CAPRISA), Durban, South Africa. 4National Cancer InstituteFrederick, Basic Research Laboratory, Frederick, United States
Presenting author email: madlalap@ukzn.ac.za
Background: Human cyclophilin A (CypA) encoded by peptidyl prolyl
isomerase A gene (PPIA), is an important cellular co-factor for
efficient human immunodeficiency virus type 1 (HIV-1) infection. In
this study we investigated the effect of genetic variation in the
regulatory region of PPIA on HIV-1 disease progression and CypA
mRNA expression levels in HIV-1 South African cohorts.
Methods: A total of 603 black South African participants from
these cohorts were genotyped for single nucleotide polymorphism
(SNP) A1650G in the regulatory region of CypA using PCR-RFLP. 247
(195 HIV-1 seronegative participants [SNs] and 52 primary infected
participants [SPs]) participants were from the CAPRISA acute infection (AI) 002 cohort and 356 HIV-1 chronically infected participants
were from the Sinikithemba cohort. CypA mRNA expression was
quantified in 30 SNs and 28 SPs from the CAPRISA AI 002 cohort by
real-time RT-PCR. Lastly, we assessed the effect of SNP A1650G on viral
(NL4.3) replication in PBMCs isolated from HIV-1 negative individuals.
Results: The minor allele (G) of SNP A1650G (referred to as 1650G)
was significantly associated with higher viral load (p B0.01) and
lower CD4 T cell count (p B 0.01) during primary HIV-1 infection.
Interestingly, the1650G was associated with rapid CD4 T cell decline
during chronic infection (p 0.01). The 1650G was also significantly
associated with higher CypA mRNA expression levels (p B0.01).
PBMCs isolated from participants harboring the 1650G supported
higher levels of NL4.3 replication ex vivo.
21
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Conclusion: Our results suggest that higher expression levels of CypA
mRNA enhance HIV-1 replication in a South African population. The
results demonstrate the clinical relevance of CypA and provide
additional in vivo validation of the CypA as a pertinent target for
therapeutic intervention. This study supports the development of
small molecule inhibitors against CypA and HIV-1 interaction.
WEPDA0101
HLA class I associations with rates of HIV-1 seroconversion
and disease progression in the Pumwani sex worker cohort
T. Peterson1, J. Kimani2,3, C. Wachihi2, T. Bielawny1, L. Mendoza4,
S. Thavaneswaran3, M. Narayansingh3, T. Kariri2, B. Liang3, E. Ngugi5,
F. Plummer3,4 and M. Luo1,3
1
National Microbiology Laboratory, HIV and Human Genetics,
Winnipeg, Canada. 2University of Nairobi, Department of Medical
Microbiology, Nairobi, Kenya. 3University of Manitoba, Department
of Medical Microbiology, Winnipeg, Canada. 4National Microbiology
Laboratory, Winnipeg, Canada. 5Universiy of Nairobi, Department of
Community Health, Nairobi, Kenya
Presenting author email: trevp.87@gmail.com
Background: Class I Human Leukocyte Antigens (HLA) play an
important role in the adaptive immune response by presenting
antigens to CD8 T-cells. Previous studies have reported multiple
HLA associations with rates of disease progression in HIV infected
individuals, while few class I associations with resistance or
susceptibility to HIV-1 infection have been reported.
Methods: HLA-A, -B, and -C were typed for more than 1000 women
enrolled in the Pumwani sex worker cohort using a sequence-based
typing method. Kaplan-Meier analysis was used to identify alleles
influencing seroconversion and disease progression to AIDS (CD4
decline to B200/mm3).
Results: A*01 (P 0.020), C*06:02 (P 0.042) and C*07:01 (P
0.050) are independently associated with protection from seroconversion. Women with any of these alleles are better protected from
seroconversion (P0.003, OR:1.988, 95% CI:1.2673.122) than those
without them. Conversely, A*23:01 (P 0.004), B*07:02 (P 0.003)
and B*42:01 (P 0.025) are independently associated with rapid
seroconversion. Women with any of these alleles are twice as likely to
seroconvert (P 0.002, OR:0.486, 95% CI:0.3040.775). The effect of
beneficial alleles in protection from seroconversion is more than three
fold when compared with those with susceptible alleles (P 0.00004,
OR:3.636, 95% CI:1.9306.852). B*14(P 0.003) and B*57:03(P
0.012) are independently associated with slower progression to AIDS,
while B*53:01(P 0.035) is associated with rapid CD4 T-cell decline.
Women with B7 supertype rapidly progressed to AIDS and individuals
homozygous for this supertype fared even worse (P0.004).
Conclusion: Understanding why these HLA class I alleles are
associated with protection/susceptibility to HIV-1 acquisition and
disease progression could contribute to the development of effective
prophylactic and therapeutic vaccines for HIV-1.
A32 - Host restriction factors including
APOBEC, TRIM and others
WEPDA0206
TRIM22 repression of HIV-1 transcription is mediated by
interaction with SP1
Track A Basic Science
A. Kajaste-Rudnitski1, S. Marelli1, G. Poli2, B. Berkhout3, A.T. Das3 and
E. Vicenzi1
1
San Raffaele Scientific Institute, Milan, Italy. 2Vita-Salute San
Raffaele University, Milan, Italy. 3University of Amsterdam,
Department of Medical Microbiology, Amsterdam, Netherlands
Presenting author email: vicenzi.elisa@hsr.it
Background: We have recently shown that the IFN-inducible
Tripartite motif-containing protein 22 (TRIM22) suppresses basal
HIV-1 LTR-mediated transcription through a Tat-and NF-kB-independent mechanism [Kajaste-Rudnitski et al., J Virol 2011, 85(10):5183
96]. In the absence of Tat/TAR RNA complex, HIV-1 transcription can
occur through the positive elongation factor (P-TEF) b function and
Sp1. We have here investigated whether TRIM22 interferes with Sp1mediated transcriptional activation of the HIV-1 LTR.
Methods: 293T cells, devoid of endogenous TRIM22, were transfected with increasing amounts of a TRIM22-expressing plasmid
together with a fixed amount of an HIV-1 LTR reporter construct that
contains a TAR sequence unresponsive to Tat and two tet-O motifs
that bind to rtTA in the presence of doxycycline (Dox). Constructs
containing the deletion of one, two or three Sp1 sites were also
tested.
Results: TRIM22 efficiently inhibited Dox-induced WT HIV-1 LTR
transcription. Interestingly, this inhibitory effect was progressively
lost with the LTR reporters lacking one, two or all three Sp1 binding
sites, respectively. In line with these observations, addition of three
Sp1 sites into a reporter construct based on a CMV-derived promoter
element, normally insensitive to TRIM22, renders it susceptible to
TRIM22 transcriptional repression, indicating that TRIM22 could have
a broader regulatory role in Sp1-mediated gene expression. Although
TRIM22 does not alter overall Sp1 expression levels when transfected
into 293T cells, immunoprecipitation experiments performed on
293T cells transfected with a FLAG-tagged TRIM22 revealed that
TRIM22 directly interacts with Sp1.
Conclusion: These results suggest that TRIM22 may inhibit HIV-1
LTR-driven transcriptional initiation through interference with the
Sp1-mediated signaling and activation of early HIV-1 gene expression, rendering it an attractive candidate for novel therapeutic
approaches.
THPDA0204
Apobec3G levels are inversely associated with resting
CD4 T memory cell integrated provirus in vivo and
infectivity of reactivated HIV-1 ex vivo
M. De Pasquale1, Y. Kourteva2, T. Allos2 and R. D’Aquila2
1
Vanderbilt University School of Medicine, Infectious Diseases,
Nashville, United States. 2Vanderbilt University School of Medicine,
Nashville, United States
Background: We hypothesized that APOBEC3G (A3G) was associated
with provirus burden in resting memory CD4 T cells, and infectivity
of HIV produced from them.
Methods: Cells from antiretroviral-naı̈ve, long-term non-progressor
(LTNP, n7) and HAART-suppressed (HS, n 11) subjects were
negatively selected from PBMCs (Robo-Sep). Sorting (FACS Aria,
BD) separated activated cells (CD25, CD69, CD38 and HLADR) from resting central memory (Tcm: CCR7, CD45RO),
resting effector memory (Tem: CCR7-, CD45RO, which includes
resting transitional memory) and resting naı̈ve (CCR7, CD45RO)
T cells. A3G was quantified by immunoblotting (Odyssey, Li-Cor).
Provirus was quantified by alu-PCR. Reactivated HIV was recovered
from cells treated ex vivo with anti-CD3,8 bispecific monoclonal
22
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
antibody and IL2. Virus p24 levels in culture supernatants were
quantified by ELISA. Infectivity of virus produced from ex vivo
activated cells was assessed using TZM-bl indicator cells.
Results: Tcm and Tem from LTNP had less provirus in vivo than the
same cell type from HS subjects (p 0.01 for Tcm and 0.02 for Tem).
A3G protein levels were higher in Tcm and Tem from the LTNP, in
comparison to Tcm and Tem from the HS, subjects (p 0.02 for Tcm
and p0.02 for Tem). Virions were recovered from ex vivo activated
Tcm from 5 of the HS subjects. Infectivities of normalized virion
amounts were inversely associated with the A3G levels in virions
produced from them (Spearman r -0.99, p0.01)
Conclusion: Resting central and effector memory CD4 T cells
from LTNP had less provirus and higher levels of A3G protein
than the same cell types from HS subjects. Infectivity of HIV
reactivated ex vivo from Tcm of HS subjects was inversely associated
with virion A3G levels. A3G appears able to restrict viral spread
from proviruses reactivated from resting memory CD4 T cells,
suggesting that improving this restriction may contribute to ’curing’
HIV.
A33 - Systems biology approaches to HIV
infection
WEPDA0201
Integration of global techniques to implicate posttranscriptional regulation in HIV infection
J. Blackinton, M. Thompson, N. Mukherjee, S. Freel, G. Tomaras and
J. Keene
Duke University, Durham, United States
Presenting author email: jeff.blackinton@duke.edu
Background: The immediate and early dynamic cellular response to
an HIV virion entering the cell is not well understood, particularly at
the post-transcriptional level where known rapid immune responses
occur. Several RNA-binding proteins (RBPs) are known to be
important in infection, including HuR, which is known to bind to
and regulate the mRNA transcripts of several of the known early
entry co-factors such as PPIA, TRIM5, APOBEC3G and CUL5.
Methods: We have previously integrated three global methods to
measure post-transcriptional regulation in Jurkat T cell activation
and examine relationships between ribonucleoprotein (RNP) interactions, transcription, RNA stability and translation. Dynamic changes
in association with HuR caused measurable effects on RNA stability
and translation of mRNAs. Transcripts that increased in association
with HuR during activation showed increased stability and translation
while those that decreased show decreased stability and translation.
Furthermore, these changed transcripts fell into relevant functional
groups, where cell cycle regulators were largely decreased in
association, stability and translation, and DNA/RNA regulators were
largely increased in association, stability and translation.
Results: To test the effect of post-transcriptional regulation in HIV
infection, we used the C8166 T cell line for a near complete and
synchronous infection and measured global changes in RNA stability
and rates of transcription using 4-thiouridine stability profiling at five
time points over the initial 24 hours of infection. Simultaneously, we
measured dynamic changes in mRNA association with HuR during
the same infection time points. Comparing the two datasets, we
observed several mRNA transcripts, including myc mRNA, a known
target of HuR, showing dynamic regulation at the level of stability
during the infection time course.
Track A Basic Science
Conclusion: Elucidation of these events supports the involvement of
the post-transcriptional response early in HIV infection and suggests
that potentially modifying or amplifying the post-transcriptional
response may be able to reduce the efficiency of infection.
A34 - Mucosal transmission
MOAA0101
The effect of liquefaction on the ability of semen and
semen amyloid fibrils to enhance HIV infection
N. Roan1,2, J. Muller3, A. Gawanbacht3, O. Zirafi3, S. Chu1,
F. Kirchhoff3, J. Munch3 and W. Greene1,4
1
The J. David Gladstone Institutes, Gladstone Institute of Virology
and Immunology, San Francisco, United States. 2University of
California at San Francisco, Department of Urology, San Francisco,
United States. 3Institute of Molecular Virology, Ulm University
Medical Center, Ulm, Germany. 4University of California at San
Francisco, Departments of Medicine, Microbiology and Immunology,
San Francisco, United States
Presenting author email: nroan@gladstone.ucsf.edu
Background: Semen, the most common vector for HIV transmission,
enhances HIV infection in vitro. We recently identified amyloid fibrils
comprised of fragments from semenogelins, the predominant
component of the semen coagulum. Semenogelin amyloids interact
with virions (Figure 1) and potently enhance HIV infection of
target cells. During semen liquefaction, semenogelins are fragmented and eventually completely degraded by PSA. We hypothesized
that if semenogelins are important for the viral enhancing activity
of semen, then the change in the levels of these proteins
during liquefaction should affect the ability of semen to enhance
infection.
Figure 1.
Roan et al.
23
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Methods: Seminal fluid liquefied for different amounts of time were
assayed for viral enhancing activity and semenogelin levels in the
absence or presence of PSA inhibitors. We also tested the effect of
purified PSA on the activity of amyloids formed from chemicallysynthesized semenogelin peptides.
Results: The viral enhancing activity of semen decreases with
increasing liquefaction time in a manner that parallels the degradation of semenogelins. Semenogelin degradation and loss of viral
enhancing activity in semen are both prevented in the presence of a
PSA inhibitor. Finally, PSA specifically cleaves and inhibits the viral
enhancing activity of semenogelin fibrils.
Conclusion: Seminal fluid’s viral enhancing activity is retained for
several hours and then progressively decreases during prolonged
liquefaction. We found a correlation between activity and semenogelin levels during liquefaction. These findings underscore the
importance of semenogelins for the viral enhancing activity of
semen. We also provide evidence that PSA directly regulates the
activity of semenogelin fibrils, suggesting that these amyloids are
regulated by liquefaction. As such, mechanisms to enhance the
natural liquefaction process may be a useful approach to limit the
ability of semen to enhance viral transmission.
MOAA0103
Impact of depot medroxyprogesterone (DMPA) on human
vaginal leukocytes and HIV-1 target cells
N. Chandra1, A. Thurman1, S. Anderson1, T. Cunningham2, C. Mauck1
and G. Doncel1
1
CONRAD, Eastern Virginia Medical School, Norfolk, United States.
2
Eastern Virginia Medical School, School of Public Health, Norfolk,
United States
Presenting author email: thurmaar@evms.edu
Background: The relationship between exogenous contraceptive
hormones and permissiveness of the female genital tract to human
immunodeficiency virus type 1 (HIV-1) remains the subject of intense
debate, due to a recent study showing a two-fold increase in the rate
of acquisition and transmission in serodiscordant couples using
depot medroxyprogesterone acetate (DMPA)[1]. In order to better
characterize the effect of DMPA on the vagina, we compared the
leukocyte populations and density of epithelial junction proteins in
vaginal tissue biopsies of women at baseline (during both the
follicular and luteal phases of the menstrual cycle) and 12 weeks
after receiving one DMPA injection.
Methods: Vaginal biopsies were obtained from 20 healthy women in
the follicular and luteal phases of the menstrual cycle, and
approximately 12 weeks after receiving a 150 milligram intramuscular injection of DMPA. Leukocyte populations, activation phenotype and epithelial thickness and tight junction and adherens
proteins were measured by immunohistochemistry and integrated
optical density. Statistical analyses were performed using Wilcoxon
signed rank tests.
Results: After DMPA administration, CD3, CD8, CD45, CD68, HLA-DR
and CCR5 bearing lymphocytes were all significantly (p B0.05)
increased in vaginal tissues, compared to the follicular and or luteal
phases. There were no significant differences in vaginal leukocyte
populations between the follicular and luteal phases of the control
cycle (p 0.05). Epithelial thickness and tight junction and adherens
proteins were not statistically different between sampling times
(p 0.05).
Conclusion: After exposure to DMPA, vaginal leukocyte populations
significantly increase in the vaginal mucosa. In absence of changes in
epithelial integrity, the increase in vaginal T cells, activation markers,
and HIV-1 receptors point to a possible immunological basis for the
Track A Basic Science
observed effects of DMPA on HIV-1 acquisition and transmission in
women.
MOAA0105
HIV-1 transmission from semen to cervicovaginal tissue
ex vivo
A. Introini1, C. Vanpouille1, A. Lisco1, J.-C. Grivel1, A. Munawwar2,
S. Singh2 and L. Margolis1
1
National Institute of Child Health and Human Development,
National Institutes of Health, Bethesda, United States. 2All India
Institute of Medical Sciences, New Delhi, India
Presenting author email: margolis@helix.nih.gov
Background: Semen is the main carrier of sexually transmitted
viruses, including HIV-1. However, semen of HIV-infected men is not
merely a passive transporter of HIV-1 but, because of its richness in
biologically-active compounds, including chemokines, may facilitate
HIV-1 transmission. To test this hypothesis and to study HIV-1
transmission under controlled conditions, we evaluated HIV-1 loads
and the cytokine milieu in semen and blood from infected men
as well as, the role of these cytokines in HIV transmission to
cervicovaginal tissue ex vivo.
Methods: We measured 21 cytokines/chemokines with a multiplex
bead assay and evaluated the loads of HIV-1 in seminal and blood
plasmas from 50 HIV-1-infected and 28 uninfected Indian men.
Results: We found that semen and blood are two separate
immunological compartments, in which concentrations of cytokines
and loads of coinfecting herpesviruses are profoundly different. Upon
HIV infection, the levels of blood and semen cytokines were
significantly altered, thus facilitating cytokine network compartmentalization. HIV-1 infection changes the seminal cytokine spectrum by
upregulating 16 of the 21 measured cytokines, while in blood 2
cytokines were downregulated and 7 were upregulated. One of the
most prominent cytokine in semen was IL-7, which was significantly
upregulated in semen of HIV-1-infected individuals. IL-7 in concentrations similar to that in semen of HIV-1-infected individuals
facilitates HIV-1 infection in cervicovaginal tissue ex vivo. This
facilitation is associated with a suppression of apoptosis of infected
CD4 T cells.
Conclusion: HIV-1 infection results in an aberrant production of
cytokines, changing the seminal cytokine network. The altered
seminal milieu is an important determinant of HIV-1 sexual
transmission: Cytokines altered by seminal infection facilitate HIV-1
transmission to cervicovaginal tissue ex vivo. Cervicovaginal tissue
infected ex vivo provides a platform to study the mechanisms of this
phenomenon and to develop new preventive strategies by targeting
the seminal microenvironment.
MOLBA03
HIV-1 female-to-male sexual transmission: evaluation of
circumcised and uncircumcised penile tissue
M. Dinh1, M. Anderson1, C. Gioia1, M. McRaven1, Z. Okocha1,
G. Cianci1, T. Hirbod2, G. Kigozi3, J. Prodger4, R. Kaul4, X. Kong5,
R. Gray5 and T. Hope1
1
Northwestern University Feinberg School of Medicine, Cell and
Molecular Biology, Chicago, United States. 2Karolinska Institutet,
Stockholm, Sweden. 3Rakai Health Sciences Program, Entebbe,
Uganda. 4University of Toronto, Toronto, Canada. 5Johns Hopkins
Bloomberg School of Public Health, Baltimore, United States
Presenting author email: m-dinh@northwestern.edu
24
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Background: Male circumcision has been shown to decrease rates of
HIV acquisition in African men. The STEP vaccine trial also demonstrated that vaccinated, uncircumcised men were at increased risk
for HIV acquisition. We sought to identify the mode(s) by which HIV
infection may occur in uncircumcised men.
Methods: Foreskins were obtained from consenting male donors
receiving prophylactic male circumcision in Rakai, Uganda. Whole
penile specimens were obtained from tissue donation organizations (ScienceCare and NDRI). Using fluorescent immunohistochemistry, foreskin keratin layers were labeled with filaggrin and
involucrin markers. Penile tissues were incubated with ex vivo
with photo-activatable GFP-linked-Vpr HIVBal for 4 hours, snapfrozen, and cryosections stained for target cells and keratin. Images
were obtained with epifluorescent microscopy and analyzed for
keratin thickness, viral particles, and viral penetration into penile
epithelia.
Results: We found no significant differences between inner and
outer foreskin keratin layers from 19 foreskin samples obtained in
Uganda, indicating that reduced keratin thickness is not likely
to make the inner foreskin more susceptible to HIV. Preliminary
data from whole penile specimens (uncircumcised n 7, circumcised
n 7) shows no significant difference in number of visualized
virions per image captured, but more virions entering uncircumcised as compared to circumcised glans tissue (uncircumcised:circumcised 2:1). Virions were found at distances from
the epithelial surface (mean9SD 33.5922.3 mm) in the range
where CD4 cells are also localized (mean9SD 53.6 932.3 mm),
in the absence of trauma to the epithelium. Finally, we visualize
virions interacting with the male urethral pseudo-stratified columnar
epithelia, though to a lesser degree than seen with stratified
squamous epithelia (n 5, glans:urethra 2:1).
Conclusion: These preliminary results suggest preferential routes by
which HIV-1 may enter the male genital tract in female-to-male HIV
sexual transmission.
A36 - Acute and early HIV infection
WEAA0105
The HIV-1 envelope protein gp120 mimics MAdCAM and
VCAM in binding to Integrin-a4b7
F. Nawaz1,2, C. Cicala1, D. Van Ryk1, D. Wei1, M. Pascuccio1,
S. Shrestha1, J. Knox1, C. Schwing1, J. Hiatt1, J. Chang1, K. Jelicic1,
A. Fauci1 and J. Arthos1
1
NIAID, National Institutes of Health, Bethesda,
United States. 2New York University School of Medicine, New York,
United States
Presenting author email: nawazf@niaid.nih.gov
Background: Our laboratory previously reported that HIV binds
and signals through Integrin-a4b7, the gut homing receptor, on
the surface of CD4 T-cells. This interaction may be critical during
the earliest events of HIV transmission, when the virus rapidly
homes to the gut and a massive depletion of gut CD4 T cells
ensues. Understanding the precise manner by which the virus
engages a4b7 may therefore provide insights into the earliest
events in HIV infection and the design of novel therapeutics. Both
its natural ligands (MAdCAM and VCAM) and gp120 bind a4b7 in
a cation-dependent manner. In each case a divalent cation bound
to the integrin coordinates an aspartic acid (Asp) residue in the
ligand. We previously described a highly conserved Asp in the V2loop of gp120 that mimics the natural ligands of a4b7, and plays
Track A Basic Science
a critical role in this interaction. However, MAdCAM and VCAM
utilize a second Asp residue and a second coordinating cation to
mediate recognition of both a4 and b7 chains in a complex way.
Our data suggests that gp120 interactions with a4b7 are similarly
complex.
Methods: To identify critical residues in HIV-gp120 that
mediate a4b7-reactivity we designed site-directed Asp mutants in
recombinant gp120s, and measured the binding of each mutant
to a4b7.
Results: By this approach, we identified two sites that mediate
gp120-a4b7 interactions. A single Asp mutant at either position
reduced reactivity with a4b7 by 2-fold relative to the wildtype,
while the double Asp mutants diminished a4b7 binding to nearundetectable levels.
Conclusion: This observation reveals the discontinuous nature
of the gp120-a47 epitope and suggests gp120 interactions with a47
closely mimic MAdCAM and VCAM. These results advance
upon our previous understanding of the molecular basis of a4b7gp120 interactions and lay the groundwork for further structural
studies.
A37 - Highly exposed seronegative
individuals (HESN)
MOAA0203
HIV-1 peptide-specific NK cell responses in HIV seropositive
and highly exposed seronegative men
R. Fecek, R. Mailliard and C. Rinaldo
University of Pittsburgh Graduate School of Public Health, Infectious
Diseases and Microbiology, Pittsburgh, United States
Presenting author email: rof19@pitt.edu
Background: Highly exposed seronegative (HESN) individuals have
had repeated exposures to HIV-1 yet remain virus and antibody
negative. We evaluated HIV-1 specific NK cell responses in men who
have sex with men (MSM) defined as HESN based on high-risk sexual
activities engaged in the early 1980’s.
Methods: Fresh, whole blood samples from HIV-1 seropositives
on ART (HIVpos), HIV-1 seronegatives (HIVneg), and HESN subjects in
the Multicenter AIDS Cohort Study were cultured with overlapping
15-mer peptide pools representing consensus sequences of
HIV-1 Gag, Env, and Reg (Tat, Rev, Vif, Vpu, Vpr), or peptide diluent
(Tiemessen, et al., JID 2010). The cultures were analyzed for
CD3-CD56 NK cell and CD3CD8 T cell responses by flow
cytometry.
Results: HIV-1 peptide-specific NK cell IFN-g and TNF-a responses
were present in 19/23 (83%) HIVpos, 6/13 (46%) HESN and 4/21
(19%) HIVneg (PB 0.001 and P 0.07 compared to HIVpos and
HESN, respectively). The IFN-g response magnitudes ranged from 1%
to 20% of all NK cells: HIVpos 5.691.1%, HESN 1.590.7%,
and HIVneg 0.4790.1% (PB 0.001 and P 0.065 compared to
HIVpos and HESN, respectively). HIVpos NK cells predominately
responded to Env peptides, whereas HESN NK cells responded to
both Env and Reg peptides. While both HIVpos and HESN
demonstrated CD8 T-cell responses to Env and Reg, only HESN
had CD8 T-cell IFN-g reactivity to Reg in association with NK cell
responses.
Conclusion: We show for the first time that contemporaneous
blood samples from MSM defined as HESN exhibit relatively
robust, innate NK cell immunity, and less common CD8 T cell
25
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
immunity, specific for HIV-1 proteins. These presumably long
lasting, NK cell responses to Env and Reg peptides could be due to
prior exposure to HIV-1, or to an inherited genetic resistance.
In-depth assessment of these virus-specific NK cell responses
could be important in designing effective HIV-1 therapeutics and
vaccines.
WEPDA0102
Highly-exposed HIV seronegative persons (HESN) had
higher levels of inflammatory and immune activationassociated serum biomarkers than lower risk HIV
seroconverters (LRSC)
O. Martinez-Maza1,2, R. Detels2, L. Magpantay3, J. Phair4,
J.H. Bream5, C.R. Rinaldo6 and L.P. Jacobson7
1
David Geffen School of Medicine at UCLA, UCLA AIDS Institute
Los Angeles, United States. 2UCLA School of Public Health,
Epidemiology, Los Angeles, United States. 3David Geffen
School of Medicine at UCLA, Obstetrics & Gynecology, Los Angeles,
United States. 4Northwestern University, Medicine - Infectious
Diseases, Chicago, United States. 5Johns Hopkins University
Bloomberg School of Public Health, Molecular Microbiology and
Immunology, Baltimore, United States. 6University of Pittsburgh,
Graduate School of Public Health, Infectious Diseases and
Microbiology, Pittsburgh, United States. 7Johns Hopkins University
Bloomberg School of Public Health, EpidemiologyUnited States,
Baltimore
Presenting author email: omartinez@mednet.ucla.edu
Background: Marked differences are seen in individuals’ susceptibility to HIV infection. Inflammation and immune activation are
critical factors contributing to initial infection with HIV. The objective of this study was to define serum levels of cytokines and
biomarkers of inflammation in participants in the Multicenter
AIDS Cohort Study (MACS) who were at high risk for acquiring HIV
infection but remained HIV seronegative (HESN), and in those at
lower risk who did (LRSC), or did not (LRSN), subsequently undergo
HIV seroconversion.
Methods: Serum levels of cytokines, and biomarkers for inflammation
were quantified using Luminex multiplexed assays, in 188 HESN, 125
LRSC, and 197 LRSN. LRSC were tested at a study visit preceding HIV
seroconversion. HESN were defined as persistently seronegative
participants who were multiply-exposed (45 anal sexual partners
in the 2.5 years prior to MACS visit 2). The LRSC and LRSN groups
hadB20 anal partners during this same period. CCR5D32
homozygotes were excluded from the HESN group. Age-adjusted
left-censored generalized gamma regression models were used to
compare levels and logistic regression models for detectability across
groups.
Results: HESN men demonstrated significantly lower age-adjusted
serum levels of APO-A1 (P0.036) and higher levels of sTNFR2
(P0.022) than LRSC. Additionally, HESN men demonstrated
significantly higher serum levels of sTNFR2 (P0.014), sCD27
(P0.035), sCD14 (P0.014), and IL-8 (P B 0.004), and lower
serum levels of CXCL13 (P 0.034) and IFNg (P0.22), than LRSN.
The likelihood of having detectable IL-2, IL-4, and IL-12 was higher in
LRSN vs HESN, but detection of these biomarkers was similar
between LRSC and HESN men.
Conclusion: HESN men displayed lower age-adjusted serum levels of
an anti-inflammatory molecule, APO-A1, and higher levels of a
molecule associated with enhanced TNF responses (sTNF-R2) than
did LRSC. These results are consistent with enhanced immune
responsiveness and inflammation being associated with resistance
to persistent infection with HIV.
Track A Basic Science
A38 - Mother-to-child transmission
WEAA0203
Target cell restriction may limit mother-to-child
transmission of SIV in sooty mangabeys
A. Chahroudi1,2, D. Carnathan2, P. Carnathan2 and G. Silvestri2
1
Emory University School of Medicine, Pediatrics, Atlanta,
United States. 2Yerkes National Primate Research Center, Atlanta,
United States
Presenting author email: achahro@emory.edu
Background: Mother-to-infant transmission (MTIT) of HIV results in
400,000 infected children each year, with a transmission rate of
3540%. In contrast, nonhuman primate species that are naturally
infected with SIV in the wild (‘‘natural hosts’’, including sooty
mangabeys, SMs) rarely transmit SIV from mothers to infants. The
mechanisms underlying this protection are unknown. In this study
we tested the hypothesis that limited target cell availability protects
SMs from MTIT.
Methods: The availability of target cells (CD4CCR5 and
CD4Ki67 T-cells) for SIV infection in seven uninfected SM infants
was measured by flow cytometry among naı̈ve and memory T-cell
subsets obtained from tissues (lymph nodes, spleen, tonsil, and
multiple sites along the gastrointestinal tract) at necropsy.
Results: We found that, in infant SMs, the median percentage of
CD4Ki67 T-cells ranged from 3.2%-10.3% depending on the anatomic site analyzed, with lower values found in CD95-CD28 naı̈ve
CD4 T-cells. In contrast, the CD95CD28CCR7 central memory
and CD95CD28CCR7- transitional memory CD4 T-cells displayed higher median levels of Ki67 (10.4%-49.3%). The percentage of
Ki67CD95CD28-CCR7- effector memory CD4 T-cells tended to
be between that of the naı̈ve cells and other memory subsets. Despite
this increased level of proliferation (compared to adult SMs), CCR5Tcells comprised B10% (and, in most cases, B5%) of the CD4
lymphocyte population at all sites and within all T cell subsets, thus
revealing restricted expression of the SIV coreceptor in infant SMs.
Conclusion: We have shown that MTIT is substantially less frequent
in SIV-infected SMs than in HIV-infected humans. Here we demonstrate that while robust T-cell proliferation is present in infant SMs,
SIV target cells (CD4CCR5 T-cells) are extremely limited in
multiple tissues. This finding reveals an additional, previously
unrecognized feature of the evolutionary adaptation to reduce the
risk of MTIT in SIV-infected SMs.
A39 - Preclinical HIV drug development
TUAA0301
Pre-clinical evaluation of HIV replication inhibitors that
target the HIV-integrase-LEDGF/p75 interaction
F. Christ1, C. Pickford2, J. Demeulemeester1, S. Shaw2,
B.A. Desimmie1, C. Smith-Burchnell2, S. Butler2, M. Westby2 and
Z. Debyser1
1
KULeuven, Laboratory for Molecular Virology and Gene Therapy,
Leuven, Belgium. 2Pfizer Inc, Sandwich, United Kingdom
Presenting author email: frauke.christ@med.kuleuven.be
Background: Current HIV-1 integrase inhibitors target the catalytic
activity, which is vital for sustained viral infection. Integrase mediates
the critical step of proviral DNA integration. Efficient integration also
26
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
requires a crucial cellular co-factor of HIV-1 integrase, LEDGF/p75,
that tethers the viral DNA to the host chromatin. LEDGINs, small
molecules designed to bind to the LEDGF/p75 interaction site on IN
and to disrupt the interaction, have recently been shown to act as
potent inhibitors of HIV replication in cell culture.
Methods: We have now analyzed the detailed mode of action of
LEDGINs, dissecting the allosteric nature of inhibition in vitro and
analyzing phenotypically their activity in cell culture. Mechanistic
studies and combination experiments shed light on potential synergy
of LEDGINs with known integration inhibitors. Analysis of the inhibition
of a broad spectrum of HIV strains allows predictions on combinations
with other drugs such as entry, RT and protease inhibitors.
Results: Biochemical evaluation of LEDGINs demonstrates in addition
to a potent inhibition of the integrase-LEDGF/p75 interaction, a block
of the catalytic integrase activities. This allosteric inhibition is
promoted by the stabilization of the dimer-interface of IN upon
LEDGIN binding most likely by affecting interaction with viral DNA.
These properties of LEDGINs result in potent inhibition of HIV
replication in both MT2 and PBMC cells. Moreover, LEDGINs are
active across a broad range of HIV clades. LEDGINs retained full
activity against a panel of viruses containing mutations that confer
resistance to integrase strand transfer inhibitors. Combining LEDGINs
with strand transfer inhibitors demonstrates a synergistic effect of
these classes of integration inhibitors.
Conclusion: The biochemical data together with the lack of cross resistance and the observed synergistic effects of LEDGINs in combination
with strand transfer inhibitors support the potential for combined use
of LEDGINs with strand transfer inhibitors in HIV therapy.
A40 - Preclinical development of
microbicides
Track A Basic Science
Bioengineering Pharmaceutics and Pharmaceutical Chemistry, Salt
Lake City, United States
Presenting author email: mclark@conrad.org
Background: Tenofovir (TFV) is the only microbicide antiretroviral that
has shown clinical effectiveness when dosed pericoitally in a vaginal
gel. There remains a need to improve TFV delivery by providing longlasting, coitally-independent, effective drug levels. Intravaginal rings
(IVRs) offer this capability; however TFV is hydrophilic and demonstrates inadequate delivery from conventional IVR technologies. Our
objective was to develop a novel IVR technology capable of releasing
]10 mg/d TFV for ]90 days, alone or co-delivered with 10 or 20 mg/d
of the contraceptive levonorgestrel (LNG).
Methods: IVRs were designed using single (TFV-only) or dual (TFVLNG) reservoir-type polyurethane (PU) segments. TFV segments
comprised water-swellable PU tubing filled with a high density TFV
paste. LNG segments comprising a LNG-loaded non-swellable PU
core with a rate controlling membrane were cut to 1 and 2 cm
lengths to obtain target release rates of 10 and 20 mg/d, respectively.
In vitro release testing (IVRT) and 3-month pharmacokinetic (PK)
studies in rabbits and sheep evaluated device performance.
Results: IVRT revealed time-independent and tunable TFV and LNG
release rates which were optimized to achieve our target 10 mg/d
TFV and 10 or 20 mg/d LNG. In sheep, TFV and LNG release rates were
estimated at 1217 mg/d and 1431 mg/d, respectively. TFV
vaginal tissue and fluid levels were 104 and 106 ng/g, respectively,
similar to levels reported after clinical dosing of TFV 1% gel. In
rabbits, LNG PK demonstrated 2-fold differences in plasma and
cervical tissue concentrations between the two dose groups, as
predicted by in vitro release.
Conclusion: We developed a unique IVR technology that met our
target product profile delivering a high flux of a hydrophilic
antiretroviral (TFV) alone or with a low flux of a hydrophobic drug
(LNG) in a controlled, time-independent manner. PK results are
highly encouraging and warrant a Phase I clinical study. [Picture of
prototype TFV and TFV/LNG IVRs]
WEPDC0103
Development of a new intravaginal ring technology for the
extended delivery of the microbicide tenofovir with and
without the contraceptive levonorgestrel
T. Johnson1, M. Clark2, J. Clark1, N. Shelke1, G. Doncel3, D. Friend2
and P. Kiser4
1
University of Utah, Bioengineering, Salt Lake City, United States.
2
CONRAD, Eastern Virginia Medical School, Obstetrics & Gynecology,
Arlington, United States. 3CONRAD, Eastern Virginia Medical School,
Obstetrics & Gynecology, Norfolk, United States. 4University of Utah,
Figure 1.
A42 - Nucleic acid-based HIV and SIV
therapies
TUAA0302
Towards HIV eradication: excision of HIV-1 proviral DNA by
Tre-recombinase in HIV-positive humanized mice
Picture of prototype TFV and TFV/LNG IVRs.
27
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
H. Hofmann-Sieber1, I. Hauber1, J. Chemnitz1, A. Grundhoff1,
J. Chusainow2, A. Schambach3, C. Baum3, P. Ziegler4, M. Manz5,
F. Buchholz2 and J. Hauber1
1
Heinrich Pette Institute-Leibniz Institute for Experimental Virology,
Hamburg, Germany. 2University of Technology Dresden, University
Hospital and Medical Faculty Carl Gustav Carus, Department of
Medical Systems Biology, Dresden, Germany. 3Hannover Medical
School, Institute of Experimental Hematology, Hannover, Germany.
4
Institute for Research in Biomedicine, Bellinzona, Switzerland.
5
University Hospital Zurich, Zurich, Switzerland
Presenting author email: helga.hofmann-sieber@hpi.uni-hamburg.de
Background: HIV-1 integrates into the host chromosome and persists
as a provirus flanked by long terminal repeats (LTR). To date, treatment
regimens primarily target the virus enzymes or virus entry, but not the
integrated provirus. Therefore, HAART requires lifelong treatment
which is frequently accompanied by the occurrence of substantial side
effects and/or the development of drug-resistant viruses. Previously,
we engineered a LTR-specific recombinase (Tre-recombinase) that
effectively excises integrated HIV-1 proviral DNA from infected human
cell cultures, suggesting that customized enzymes might someday
help to eradicate HIV-1 from the body. Therefore, we here analyzed
the potential of Tre-recombinase to reverse HIV-1 infection in vivo.
Methods: We constructed an advanced lentiviral self-inactivating
(SIN) vector that expresses Tre-recombinase conditionally in HIVinfected cells. We monitored Tre functionality and potential Trerelated cytopathic effects over time in tissue cultures. Moreover, the
effect of Tre activity on HIV-1 infection was investigated in
humanized mice.
Results: It is shown that Tre-recombinase is efficiently delivered into
cells and accurately excises HIV-1 proviral DNA from chromosomal
integration sites. Apparently, prolonged overexpression of Tre-recombinase does not induce undesired cytopathic effects in the transduced
cells. Finally, we demonstrate pronounced antiviral activity of Trerecombinase in HIV-1 infected Rag2 / ?c / mice, which were
either engrafted with Tre-transduced human CD4 T cells or with Tretransduced human CD34 hematopoietic stem cells (HSC).
Conclusion: The presented data suggest that Tre-recombinase may
be a valuable component of future antiretroviral therapies of the
post HAART era that aim at virus eradication, thereby providing a
cure for AIDS.
TUAA0303
In vivo suppression of HIV by antigen specific T cells derived
from engineered hematopoietic stem cells
S. Kitchen, B. Levin, G. Bristol, V. Rezek, S. Kim, C. Aguilera-Sandoval,
A. Balamurugan, O. Yang and J. Zack
David Geffen School of Medicine at UCLA, UCLA AIDS Institute,
Los Angeles, United States
Presenting author email: skitchen@ucla.edu
Background: In HIV infection, the HIV-specific cytotoxic T lymphocyte
(CTL) response is a critical component in controlling viral replication
that ultimately fails in its ability to eradicate the virus from the body.
Our primary aim is the development of a way to enhance the HIVspecific CTL response to allow long-term viral suppression or viral
clearance.
Methods: In our approach, we sought to genetically manipulate
human hematopoietic stem cells (HSCs) such that they differentiate
into mature CTLs that will kill HIV infected cells. To perform this, we
utilized molecularly cloned HIV-specific T cell receptors (TCRs) derived
from CD8 T cells. These TCRs were used to genetically transduce
HSCs that were introduced into a humanized mouse and were allowed
Track A Basic Science
to differentiate into mature human CD8 CTLs. Mice expressing the
transgenic HIV-specific TCR and, separately, control mice were then
infected with HIV-1 and functional cellular responses, viral suppression, and viral and T cell dynamics were assessed.
Results: We found that genetic modification of human HSCs with a
cloned TCR allows proper differentiation of the cells to occur in vivo
and these cells migrate to multiple anatomic sites, mimicking what is
seen in humans. We observed that the genetically modified HIVspecific CTLs form a functional antiviral response in vivo that results
in the significant suppression of HIV replication in multiple organs. In
addition, we found significant correlations between the levels of
reconstitution with cells bearing the HIV-specific TCR, antigen-driven
T cell expansion, and the control of viral replication.
Conclusion: We have developed a system to closely characterize the
engineering of antiviral immunity and HIV-specific CTL responses.
Our results strongly suggest that stem cell based gene therapy may
be a feasible approach in the treatment of chronic viral infections
and provide a foundation towards the development of this type of
strategy.
THPDA0202
Hematopoietic stem cell gene therapy targeting HIV-1 based
on lentiviral CCR5D32 and multiple microRNAs
L.-J. Chang1, G. Alkhatib2, L.-M. Huang3, Y. Chen1 and Y. Yeh1
1
University of Florida, Molecular Genetics and Microbiology,
Gainesville, United States. 2Texas Tech University Health Sciences
Center, Biomedical Sciences, El Paso, United States. 3National Taiwan
University, Pediatrics, Taipei, Taiwan, Province of China
Presenting author email: lchang@mgm.ufl.edu
Background: Treatment of HIV infection by antiretroviral therapy is
effective but costly and often associated with numerous side effects.
The key to a permanent treatment to chronic HIV infections is to
elicit potent host resistance to viral infection and to restore immune
functions. The prolonged incubation period of HIV-1 provides a good
opportunity for applying non-conventional interventions such as
gene therapy. For HIV gene therapy to be effective, the combination
of an efficient gene transfer vector and a powerful anti-HIV strategy
is necessary.
Methods: HIV resistance will be established in patients? hematopoietic stem cells (HSCs) by lentivector (LV) transduction of (i) a
microRNA to block endogenous CCR5 expression, (ii) a sequencemodified CCR5D32 gene to interfere with the function of native
CCR5 and CXCR4 and (iii) effective multiple anti-HIV shRNAs to target
viral RNAs.
Results: We generated LVs encoding the native and a codonoptimized CCR5D32 gene. Ectopic expression of CCR5D32 in HOSR5 and Magi-R5 cells established protection against R5-HIV-1
infection. Unexpectedly, we observed severe cytotoxicity in HOS-R5
cells and primary CD4 T cells when CCR5D32 was expressed. In a
second approach, we generated a LV expressing an H1-promoter
driven CCR5 miRNA and demonstrated marked protection against
R5-HIV-1 infection. In a third approach, we generated a novel LV
expressing three miRNA intronic cassettes (miR155-19a-30a) targeting HIV-1 pol, int and vpu, respectively, and demonstrated marked
protection against HIV-1 infection. LV transduction of adult CD34
HSCs had no adverse effect on hemopoiesis for dendritic cell
development but T cell development appeared to be impaired based
on an in vitro assay.
Conclusion: We conclude that ectopic expression of CCR5D32 in
adult CD34 HSCs using a constitutive expression promoter is
cytotoxic because the CCR5D32 transgene can activate uncontrollable intracellular T cell signaling. However, miRNAs targeting
28
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
endogenous CCR5 and multiple HIV sequences is highly effective
against HIV infection without cytotoxicity.
A43 - B cell-based vaccines
MOLBA05
Stabilized exposure of conserved epitopes by structure
guided insertion of disulfide bonds in HIV envelope
glycoprotein
A. Dey1, A. Kassa1, A. Nandi1, P. Sarkar1, Y. Sun2, K. Hartog2,
C. Labranche3, D. Montefiori3, I. Srivastava4, A. Carfi1 and S. Barnett1
1
Novartis Vaccines & Diagnostics Inc., Cambridge, United States.
2
Novartis Vaccines & Diagnostics Inc., Emeryville, United States.
3
Duke University Medical Center, Durham, United States. 4Vaccine
Research Center / NIAID/NIH, Vaccine Production Program
Laboratory / VRC/NIAID, Bethesda, United States
Presenting author email: antu.dey@novartis.com
Background: The transition from native to receptor-bound and
eventually to the fusion-competent conformation of HIV-1 envelope
glycoprotein (Env) Env requires a tightly choreographed interaction
among highly conserved structures within the viral envelope
glycoprotein. Recent structural information has revealed that these
conformational transitions are regulated by three conserved but
highly mobile layers stacked between the receptor-binding domain
(gp120) and the fusion arm (gp41) of Env. We hypothesized that
limiting the mobility of these layers by artificially insertion of
covalent bonds will capture Env in a conformation where conserved
sites are stably exposed.
Methods: We scanned residues that lie at the interface of gp120
layers (layers 1, 2 and 3) and identified targets that are predicted to
form disulfide bonds if substituted with paired cysteines. We
substituted a pair of residues between layers 1 and 2 with cysteine
& expressed and purified the disulfide-stabilized gp120 (and gp140)
antigens and analyzed them using Surface Plasmon Resonance (SPR)
assay. Following in vitro analysis, we immunized rabbits with both
the wild-type and disulfide-stabilized gp120 (and gp140) antigens,
adjuvanted with CarbopolMF59, and evaluated serum antibodies
for binding, neutralization and epitope-specificity.
Results: A single disulfide bond inserted between the highly
conserved layers 1 and 2 led to enhanced stability of the receptor
bound conformation of gp120. This was revealed by lower dissociation constant (Kd) of the mutant gp120 binding to 17b antibody,
which recognized a conserved CD4 induced (CD4i)-epitope on gp120.
Upon immunization in rabbits, the disulfide-stabilized gp120 (and
gp140) antigens, in comparison to wild-type antigens, elicited higher
level of antibodies directed to CD4-binding site and CD4i-site.
Conclusion: We demonstrate that structure guided stabilization of
inter-layer interactions within Env can be used to improve and
stabilize the exposure of conserved epitopes on the antigen and elicit
improved antibody response, with the aid of a potent adjuvant, upon
immunization.
TUPDA0103
Novel DNA vaccine candidates that mimic the
neutralization-competent structure of the MPER of
HIV-1 gp41
N. Gulzar1, M. Montero1, K.-A. Klaric1, C. Lepik1, J. Donald2, S. Tsai1,
S. Wu1, S. Wang3, W. Degrado4, S. Lu3 and J.K. Scott5
Track A Basic Science
1
Simon Fraser University, Burnaby, Canada. 2University of
Pennsylvania, Philadelphia, United States. 3University of
Massachusetts Medical School, Worcester, United States. 4University
of California-San Francisco, San Francisco, United States. 5Simon
Fraser University, MBB/FHS, Burnaby, Canada
Presenting author email: jkscott@sfu.ca
Background: The limited success of vaccines targeting the MPER of
HIV-1 gp41, we hypothesize, may in part reflect the difficulty of
mimicking its neutralization-competent structure (NCS). We have
developed DNA-vaccine candidates meant to emulate the NCS of the
MPER, and report on their ability to elicit MPER-specific, neutralizing
(Nt) antibodies (Abs).
Methods: DNA vaccines encoding various gp41 ectodomain fragments, and the transmembrane region (TM) of either the plateletderived growth factor receptor (PGDFR), or that of gp41 were
engineered, transiently expressed in COS-7 cells, and tested for
antigenicity. Rabbits were immunized with plasmid DNA of select
candidates; sera were collected and tested for MPER reactivity.
Results: Work with the protein products of these vaccines has shown
they mimic the NCS of the MPER by several criteria, including the
ability to be bound tightly by well-characterized Nt MAbs, but weakly
by their non-neutralizing mutant-MAb counterparts. Immunizations
with plasmids expressing the MPER tethered to the PDGFR-TM
elicited MPER-specific Abs that targeted the epitope of the 2F5 NtAb.
Immunization with DNA vaccines encoding the MPER and gp41 TM,
elicited low-titre Abs that cross-reacted weakly with the MPER, and
strongly with regions outside the MPER. Both sets of immunizations
failed to produce Abs that cross-reacted with the 4E10 epitope, or
neutralized pseudoviruses bearing HIV-1 Env. We found that the
presence of the PGDFR-TM significantly reduced MPER-binding to
4E10 MAb, but not by 2F5. Putative models suggest that in the
PDGFR-TM fusions, the 4E10 epitope faces into the lipid bilayer,
thereby altering its exposure.
Conclusion: Our work reveals key structural features involved in
promoting the NCS of the MPER. While the gp41 TM is vital in properly
exposing neutralizing epitopes on the MPER, it was also found to
elicit Abs against sites outside the MPER. Current work is focused on
engineering the gp41 TM to optimally expose MPER epitopes.
A44 - T cell-based vaccines
WEAA0102
A novel HIV vaccine approach: targeting the protease
cleavage sites of HIV-1
M. Luo1,2, D. Tang1, R. Capina1, X.-Y. Yuan1, C. Prego3, J.C. Pinto3,
M. Alonso3, C. Barry1, R. Pilon1, C. Daniuk1, J. Tuff1, S. Pillet1, D. La1,
T. Bielawny1, C. Czarnecki1, P. Lacap1, H. Peters1, G. Wong1,
M. Kimani4, C. Wachihi4, J. Kimani2,4, T. Ball1,2, P. Sandstrom1,
G. Kobinger1,2 and F. Plummer1,2
1
National Microbiology Laboratory, HIV and Human Genetics,
Winnipeg, Canada. 2University of Manitoba, Medical Microbiology,
Winnipeg, Canada. 3University of Santiago de Compostela, Pharmacy
and Pharmaceutical Technology, Santiago, Spain. 4University of
Nairobi, Nairobi, Kenya
Presenting author email: ma.luo@phac-aspc.gc.ca
Background: The classical vaccine approach for combating other
viruses has failed so far in dealing with HIV-1, a virus infecting a key
component of immune system and with greater diversity and rapid
mutation. New approaches are needed to develop a preventative
vaccine.
29
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
The protease of HIV-1 is a small 99-amino acid aspartic enzyme
mediating the cleavage of Gag, Gag-Pol and Nef precursor polyproteins. The process is highly specific, temporally regulated and
essential for the production of infectious virions. A total of 12
proteolytic reactions are required to generate a viable virion.
Therefore, a vaccine targeting the 12 protease cleavage sites(PCS)
could be effective. The PCS of HIV-1 are highly conserved, direct
immune responses against these sites would yield several advantages. First, the immune response could destroy the virus before its
establishment in the host. Second, it could force the virus to
accumulate mutations eliminating the normal function of the HIV
protease. Third, restricting the immune responses to these sites can
avoid distracting immune responses that often generate unwanted
inflammatory responses, induce excess immune activation, and
attract more targets for HIV-1 infection, establishment and spread.
Methods: We conducted a pilot study to investigate the feasibility
and effectiveness of this approach. The recombinant VSV-peptides
were used to immunize cynomolgus macaques and nanopackaged
peptides were used to boost the immune response to the
12 PCS of SIVmac239. The controls and immunized macaques were
repeatedly challenged intrarectally with an increased dosage of
SIVmac239.
Results: Antibody and T cell responses to the 12 PCS can protect
macaques against higher dosage of SIVmac239 challenge (p 0.0005,
R0.8005) and the vaccine group maintains significantly higher
CD4 counts (p 0.0002) than the controls weeks after being
infected. Population coverage analysis showed that this approach
can be applied to 95% populations in the world.
Conclusion: Targeting 12 PCS of HIV-1 is a viable approach.
A45 - Novel vectors and strategies
WEAA0101
Characterization of early gene expression profile in the
blood of macaques immunized a Thai trail-like vaccine
M. Vaccari1, M. Cameron2, N. Liyanage1, P. Pegu1, S. Gordon1,
M. Doster1, R.-P. Sekaly2 and G. Franchini1
1
National Institute of Health, Bethesda, United States. 2VGTI-Florida,
Port St Lucie, United States
Presenting author email: vaccarim@mail.nih.gov
Background: A strategy combining Canarypox based vaccine, ALVACHIV with gp120 protein has resulted in limited but significant
protection from HIV infection in The RV144 vaccine efficacy trial.
We have previously tested a similar strategy in the non-human
primate model of HIV infection obtaining a similar efficacy to what
observed in humans.
Methods: To study the contribution of innate immune responses
as correlate of protection, we have performed microarray analysis
in the blood collected from 6 macaques at 16, 24 48 and 72 hours
after the first two immunizations with ALVAC (V1 and V2 respectively) and the 3rd immunization with ALVAC/gp120 protein (V3).
Results: Our results show that 1) 24h after the 1st immunization with
ALVAC-SIV (V1) genes with antiviral activity were up regulated (MX1,
HERC-5, CD79b), but interestingly inflammatory genes where down
regulated (IL1, IL18RAP, IFNR1), suggesting a reciprocal regulation of
genes for IFN type I and II; 2) similar patterns of gene expression
where observed earlier, at 16h from V2, suggesting the presence
of "memory -innate" anti viral responses; 3) the 3rd boost with
ALVAC, given simultaneously to the gp120 protein adjuvanted in
Alum (V3), resulted in significant changes in the gene expression
Track A Basic Science
profile when compared to the first two vaccinations. At 24h from this
immunization there were a far less number of IFN-related genes that
were significantly up regulated (V3 3) when compared to the first
and second immunization (V1 17; V2 27), and the IFN-responses
still up regulated were associated with NK cells, B cell- (CD79B) and
T cell- (PKC, CD28 TCR) responses.
Conclusion: These results suggest that each component of vaccination could have contributed to the protection from infection
underscored the ALVA/gp120 strategy. Understanding how to induce
different types of immune responses that are protective for
HIV may be relevant for the generation of more effective vaccine
strategies.
A53 - Mycobacteria and tuberculosis
THPDA0101
Peripheral blood monocytes contribute to the immune
reconstitution inflammatory syndrome (IRIS): is the
complement system emerging to the spotlights?
H. Tran Thi Thanh1,2, R. Van den Bergh1,2, L. Kestens3, M. MassingaLoembe3, R. Colebunders3, P. De Baetselier1,2, G. Raes1,2 and TB-IRIS
Study Group
1
Vrije Universiteit Brussel, Cellular and Molecular Immunology Unit,
Brussels, Belgium. 2Myeloid Cell Immunology Laboratory, VIB,
Brussels, Belgium. 3Institute of Tropical Medicine, Antwerpen,
Belgium
Presenting author email: thitran@vub.ac.be
Background: One of the most frequent complications associated
with antiretroviral therapy (ART) in HIV-tuberculosis (TB) co-infected
patients is the Immune Reconstitution Inflammatory Syndrome
(IRIS). While monocytes/macrophages play a major role in both
HIV- and TB-infection individually, the putative contribution of
monocytes to the development of TB-IRIS remains uncharacterized.
We therefore applied a parallel approach of genome-wide microarray
analysis and focused gene expression profiling in monocytes from
Ugandan HIV-TB co-infected patients before and shortly after ART
initiation, to investigate the possible functional contribution of
monocytes to the development of IRIS.
Methods: Monocyte gene expression of TB-IRIS patients and non-TB†
IRIS patients was analyzed by Affymetrix GeneChip Human Gene
1.0 ST Arrays and was confirmed using the nCounter system; datasets
were analyzed for overrepresented pathways using Ingenuity Pathway Analysis. Expression levels of and enzymatic activities of proteins
of interest were characterized in the isolated monocyte fractions and
in the plasma of IRIS patients.
Results: Pathway analysis indicated that the complement system was
significantly modulated in monocytes of TB-IRIS patients, both before
initiation of therapy (baseline) and after two weeks of therapy. At
baseline, expression of both C1q and C1-inhibitor was higher in TBIRIS patients. After two weeks, the C1q mRNA levels in the majority
of TB-IRIS patients increased, whereas C1-inhibitor mRNA levels
decreased pronouncedly. Additionally, the inhibitory activity of C1inhibitor was significantly higher in TB-IRIS patients compared with
non-TB-IRIS patients at baseline but reduced to the level of C1inhibitor activity in non-TB-IRIS patients at week 2.
Conclusion: For the first time, we provide evidence that monocytes
at least partially contribute to the development of TB-IRIS, probably
through the complement system response. An intriguing possibility
is that the relative balance between C1q and C1-inhibitor may
be affecting the inflammatory function of C1q in the complement
cascade.
30
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
A55 - Interactions with other pathogens
THPDA0102
Cytokine storm in leishmania/HIV-1 co-infected patients can
be caused by LPS and leishmania infection
J. Santos-Oliveira1, C. Giacoia-Gripp1, E. Regis1, P. AlexandrinoOliveira2, V. Amato3, J.A. Lindoso3, H. Goto3, J. Guerra4, M. Mattos1,
M. Oliveira-Neto1, B. Grinzstejn1, M. Morgado1 and A. Da-Cruz1
1
Oswaldo Cruz Foundation/ FIOCRUZ, Rio de Janeiro, Brazil. 2Federal
University of Mato Grosso do Sul, Rio de Janeiro, Brazil. 3University
of Sao Paulo (USP), Sao Paulo, Brazil. 4Tropical Medicine Foundation,
Manaus, Brazil
Presenting author email: joanna_reis@yahoo.com.br
Background: We have shown that leishmaniasis contributes to
heightened T-cell activation in HIV-1/Visceral leishmaniasis (AVL)
patients. Now we investigate whether lipopolysaccharide (LPS) has a
crucial role in the pathogenesis of this co-infection.
Methods: 10 healthy volunteers, 17 AVL/HIV-1 and 16 HIV-1/AIDS
patients were recruited. CD4T counts and CD8T cells expressing
CD38 were analyzed by flow cytometry. LPS and sCD14 levels were
measured by enzymatic assays. Plasmatic pro-inflammatory cytokines (IL-1/IL-6/IL-8/IL-17/IFN-g/TNF-a) were assessed by multiplex
analysis. The macrophage migration inhibition factor (MIF) and
intestinal fatty acid binding protein (IFABP) were quantified by
ELISA. Mann-Whitney and Spearman correlation test were employed
for statistical analysis. Multivariate linear regression was used to
determine influence of intervenient factors over T-cell activation.
Results: AVL/HIV-1 patients in leishmaniasis remission presented
equal CD4T counts or T-cell activation levels in comparison to
patients in the active phase of leishmaniaisis. Higher levels of CD8/
CD38 were seen independently of leishmaniasis clinical phase
when compared to HIV/AIDS cases (p B 0.05). Viral load levels had
no influence in CD8/CD38 levels. Co-infected and HIV patients
presented similar LPS and IFABP levels, but higher than healthy
donors (pB 0.001). Pro-inflammatory cytokines levels, but not MIF
were significantly augmented in co-infected cases. LPS levels
were positively correlated with MIF (r 0.40;p B 0.05). We found
positive correlation between LPS levels and CD38 on CD8 T
lymphocytes(pB0.001), independently of CD4 T counts, HIV
viremia, sCD14, MIF and IFAB levels. Leishmania infection was also
positively correlated with activation levels(p B 0.001). We also
observed that LPS and Leishmania infection were positively correlated with IL-6(p B 0.05) and IL-8(p B 0.01) levels.
Conclusion: Leishmania/HIV-1 patients had an exacerbated proinflammatory cytokine response. In addition, LPS contributes to
higher T-cell activation. In conclusion, Leishmania infection along
with LPS levels may contribute to cytokine storm, which in turn may
increase T-cell activation, worsening the condition of patients
harboring both pathogens.
THPDA0104
HIV-facilitated paracellular penetration of HPV into mucosal
epithelium
S. Tugizov1, R. Herrera1, P. Veluppillai2, D. Greenspan2 and J. Palefsky1
1
University of California at San Francisco, Medicine, San Francisco,
United States. 2University of California at San Francisco, Orofacial
SciencesSan Francisco, United States
Presenting author email: sharof.tugizov@ucsf.edu
Background: The incidence of HPV-associated lesions is higher in
HIV-infected than in HIV-uninfected individuals. Oral and anogenital
Track A Basic Science
mucosal epithelia of HIV/AIDS-positive individuals contain infiltrating
HIV-infected immune cells that express viral tat and gp120, and
proinflammatory cytokines TNF-a and IFN-g. These proteins may
disrupt tight junctions (TJ) of mucosal epithelium, facilitating HPV
penetration. Our aims were to investigate how HIV-associated
disruption of mucosal epithelium promotes HPV infection.
Methods: Polarized oral and cervical epithelial cells and tissue
explants from HIV-uninfected individuals were treated with recombinant HIV-1 tat, gp120, TNF-a and IFN-g independently and together.
The cells and tissue explants were exposed to HPV 16 pseudovirions
labeled with fluorescent dyes. Paracellular HPV penetration through
disrupted epithelium was evaluated by confocal microscopy.
Results: Treatment of oral and cervical epithelial cells with tat,
gp120, TNF-a, or IFN-g independently for 24 h did not induce
significant disruption of TJ but the combination of all 4 proteins
caused disruption of TJ in about 90% of cells. Prolonged treatment of
cells with these proteins independently for 5 days also induced
substantial disruption of TJ. Epithelial disruption mediated by these
proteins facilitated paracellular PsV passage through polarized cells30-45% of apically applied virions were detected in the basolateral
compartment. Treatment of oral epithelial explants with HIV tat,
gp120, TNF-a, and IFN-g led to disruption of epithelial TJ with
paracellular HPV penetration into epithelium and entry of HPV into
basal cells.
Conclusion: Our data indicate that HIV tat, gp120, TNF-a, and/or
IFN-g in the epithelial microenvironment disrupt epithelial TJ in a
time-dependent manner. Alone or together, they potentiate HPV
penetration into basal epithelial cells where HPV infection is
initiated. Interference with the effects of these proteins may be
useful to reduce the risk of HPV infection when applied topically to
at-risk genital mucosal epithelium prior to sexual exposure.
THPDA0105
Prevalence and genotypic variability of TT virus are
extremely high in HIV-1-infected adults in the Lampang HIV1 cohort in northern Thailand
H. Thaisri1, M. Moriuchi2, N. Tsuchiya3, A. Rojanawiwat1,
P. Pathipvanich4, P. Sawanpanyalert1, K. Ariyoshi3 and H. Moriuchi2
1
National Institute of Health, Bangkok, Thailand. 2Nagasaki University
Graduate School of Biomedical SciencesDepartment of Molecular
Microbiology and Immunology, Nagasaki, Japan. 3Nagasaki
University, Institute for Tropical Medicine, Nagasaki, Japan. 4Lampang
Hospital, Lampang, Thailand
Presenting author email: hiromori@nagasaki-u.ac.jp
Background: TT virus is genetically variable and widespread among
the general population without apparent pathological effects. It has
been detected in the peripheral blood and a variety of body fluids
such as semen and cervical fluids. Studies from North America and
Europe have reported that TTV infection is more prevalent in HIV-1infected individuals than in healthy control, but its prognostic
significance has been controversial. No study has been reported
for TTV co-infection in HIV-1-infected Asian people. This study was
aimed to demonstrate prevalence, genotypic variability and prognostic significance of TTV coinfection in northern Thailand HIV
cohort.
Methods: A total of 756 HIV-1-infected adults were enrolled in the
Lampang HIV cohort in northern Thailand, and their blood samples
were collected. HIV-1 plasma viral loads and CD4 counts were
measured at enrollment, and their clinical courses had been
monitored. 40 healthy Japanese adults were also tested as controls.
DNA of 5 TTV genogroups (G1 to G5) was detected by PCR using
genogroup-specific primer pairs.
31
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Results: 753 (99.9%) of 754 HIV-1-infected adults were infected with
any genogroup of TTV: G1 (700/754, 93%), G2 (0/754, 0%), G3a (740/
754, 98%), G3b (732/754, 97%), G4 (601/754, 80%) and G5 (562/754,
75%). On the other hand, 38 (95%) of 40 healthy Japanese adults
were infected with any TTV genogroup: G1 (63%), G2 (3%), G3a
(70%), G3b (68%), G4 (63%) and G5 (20%). Infection with more than
one genogroup is more common in HIV-1-infected adults (99%) than
in controls (68%). 62% HIV-1-infected and only 13% healthy adults
were infected with all of G1, G3a, G3b, G4 and G5.
Conclusion: TTV infection is highly prevalent in both HIV-1-infected
and uninfected Asian adults; however, mixed genogroups were much
more common in the former. Correlations between certain TTV
genogroup or TTV loads and CD4 counts or HIV-1 load will be
determined.
Track A Basic Science
Conclusion: We have developed a versatile secretion capture assay,
which allows the detection of any secreted protein of interest, and
does not compromise cell viability. This method is useful in understanding modifications to cytokine secretion induced by viruses such
as HIV-1.
A57 - Novel assays for virological
monitoring
TUPDE0203
Evaluation of the use of dried blood spots for viral load
monitoring in resource-limited settings in Zimbabwe
A56 - Novel assays of immune responses
TUAA0105
A universal nanoparticle cell secretion capture assay for the
study of HIV-1-positive tissues
W. Fitzgerald and J.-C. Grivel
NIH, NICHD, Bethesda, United States
Presenting author email: grivelj@mail.nih.gov
Background: Secreted proteins play an important role in intercellular
interactions, especially between cells of the immune system.
Infection of human lymphoid tissues by HIV-1 may alter secretion
patterns. Here, we describe a novel, easy, inexpensive, and versatile
method, which allows the identification and isolation of a living cell
actually secreting any protein of interest.
Methods: We coupled carboxylated magnetic iron oxyde nanoparticles (IONPs) or quantum dots to polyclonal goat anti-mouse
IgG(HL) antibodies (GAM) and used them as a platform to bind
a cell-specific antibody, conferring cell targeting, and an antibody
specific for a secreted protein. Purified complexed IONPs form an
affinity matrix on the cell surface and capture the cell-secreted
product, which can then be detected on the surface of the secreting
cell by another secreted-protein-specific labeled antibody.
Results: GAM-IONPs complexed with anti-CD45 antibody and either
anti-IL-2 or anti-IFNgamma. This capture assay was as efficient as a
commercial assay and intracellular cytokine staining in identifying
cells that secrete IL-2 and IFNg. Respectively, these assays detected
IL-2 secretion on 16.994%, 14.791.8% and 16.391.4% of T cells
(N 6, P B0.88) in activated PBMC cultures. Similarly, IFNg secretion
was detected equally by these three assays. Quantum dots can be
used in place of IONPs and allowed similar detection of cytokines as
well as fluorescent targeting of cells. The capture assay also detected
the secretion of MIP-1a, MIP-1b and RANTES for which no
commercial assays are available, and levels were comparable to
intracellular staining. This method is amenable to multiplexing and
several cytokines may be detected on the same cells.
S. Ngwende1, B. Mudenge2, D. Madzimure2 and G. Mudenge2
1
National Microbiology Reference Laboratory, Ministry of Health and
Child Welfare, Harare, Zimbabwe. 2Flow Cytometry Laboratory,
Harare, Zimbabwe
Presenting author email: stngwende@gmail.com
Background: Monitoring of antiretroviral treatment (ART) with
human immunodeficiency virus (HIV) viral loads, is rarely available
in resource-limited settings because of the high costs, stringent
requirements for storage and transport of plasma. Monitoring of
antiretroviral therapy (ART) with HIV-1 viral load assays to determine
virological treatment failure and to decide when to change to second
line therapy is highly recommended. Requirements for -80 degrees
Celsius freezers for sample storage prohibit implementation of this
level of care in resource poor settings. Dried blood spots (DBS) can
be used as an alternative to plasma, but the use of DBS for HIV-1
assays has not been assessed in Zimbabwe. This study investigates
the performance of DBS for HIV viral load monitoring of patients on
ART in Zimbabwe.
Methods: Parallel forty eight (48) plasma samples and 48 DBS
samples were used in this study. They were selected from samples
stored at Flow Cytometry Laboratory, Zimbabwe, collected from
patients with ART failure and who were being monitored for HIV
drug resistance. Viral load assays were performed on 48 samples
using plasma and dried blood spots methods. Plasma was separated
and frozen at -80 degrees Celsius and DBS were kept at room
temperature for 30days.
Results: The correlation between plasma and DBS viral load was high
(R2 0.75). Mean difference was 0.05 log10 copies/mL (SD 0.58),
and only 8 samples showed 1 log10 difference. Sensitivity and
specificity of DBS to detect virological failure (plasma viral load
400 copies/mL) was 82.5 and 93.1%, respectively.
Conclusion: There was a very good correlation between DBS stored
at room temperature for 30 days and plasma viral load assays. The
evaluation shows that DBS can be a feasible and reliable method for
virological monitoring of patients on ARVs in rural areas with
transport facilities for referring samples to a central laboratory.
Abstract Coding Guide
Example: MOAA01(Weekday) MO (Session type) AA (Session order) 01
Weekdays: SU (Sunday), MO (Monday), TU (Tuesday), WE (Wednesday), TH (Thursday), FR (Friday)
Session types: oral abstract sessions AA (Track A), AB (Track B), AC (Track C), AD (Track D), AE (Track E), AX (Cross-Track), LBA (Late
Breaker Track A), LBB (Late Breaker Track B), LBC (Late Breaker Track C), LBD (Late Breaker Track D), LBE (Late Breaker Track E), LBX (Late
Breaker Cross-Track); oral poster discussions sessions PDA (Track A), PDB (Track B), PDC (Track C), PDD (Track D), PDE (Track E) PDX
(Cross-Track)
Session order: 01, 02, 03, 04, etc.
32
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
http://www.jiasociety.org/index.php/jias/article/view/18439 | http://dx.doi.org/10.7448/IAS.15.5.18439
Track B Clinical Science
3
B1 - Impact of co-factors: viral clade,
tropism, genetic factors, age and gender
on disease progression
MOAB0104
Toll-like receptor 4 polymorphism influence the
development of opportunistic diseases in HIV-positive
patients
T. Kyrychenko1, G. Dubynska2, T. Koval2, I. Kaidashev2 and
V. Korshenko1
1
Poltava Regional HIV/AIDS Prevention and Control Center, Poltava,
Ukraine. 2Ukrainian Medical and Dental Academy, Poltava, Ukraine
Presenting author email: loyal7@rambler.ru
Background: Toll-like receptors (TLRs) are transmembrane receptors
that activate cells of the innate immune systems upon recognition
of pathogen-associated molecular patterns. The TLR4 is an essential
component of the innate immune response to various microorganisms. We investigated the impact of TLR4 polymorphism on
development of opportunistic diseases in HIV-infected patients.
Methods: The presence of TLR4 Asp299Gly single nucleotide
polymorphisms (SNPs) was determined in a cohort of 180 antiretroviral treatment-naive HIV-1 infected patients and evaluated in
relation to the occurrence of opportunistic infections. TLR4 genotyping was performed by real-time PCR.
Results: One hundred sixty-five patients were homozygous for the
wild-type genotype (AA); 15 patients (8,3%) were heterozygous for
the Asp299Gly SNP (AG).
TLR4 polymorphism was associated with more frequent development of the opportunistic infections, such as active tuberculosis
(OR 3.27; 95% CI [1.2110.29]), herpes zoster (OR 4.15; 95% CI
[1.247.29]) and toxoplasmosis (OR 6.23; 95% CI [1.1918.67])
compared with genotype AA.
In addition, TLR4 SNP was associated with development of
opportunistic diseases among individuals with CD4 cell count
of 100 cells/mm3, compared with homozygous HIV-infected patients (OR, 5.25; 95%, CI [2.2810.47]).
Conclusion: This study suggests a greater risk of developing of active
tuberculosis and other opportunistic infections in patients with the
Asp299Gly TLR4 polymorphism.
B2 - Acute and early infection
TUPDB0202
Prospective detection and description of acute HIV infection
in a high risk cohort of women in resource-limited settings:
identifying factors that contribute to the continued spread
of HIV
K. Rono1, H. Kibuuka2, L. Maganga3, J. Kosgei1, A. Sekiziyivu2,
E. Sanga3, E. Ngetich1, A. Bolen Valenzuela4, N. Michael4 and
M. Robb4
1
Kenya Medical Research Institute-Walter Reed Project, Kericho,
Kenya. 2Makerere University Walter Reed Project, Kampala, Uganda.
Mbeya Medical Research Programme, Mbeya, United Republic
of Tanzania. 4US Military HIV Research Program, Bethesda
United States
Presenting author email: krono@wrp-kch.org
Background: Diagnosis of acute HIV infection (AHI) is uncommon in
resource limited settings. This abstract describes acute HIV infection
in women in three East African countries.
Methods: Women at high risk of infection were recruited from ‘hot
spots’ in Kericho (rural Kenya), Kampala (urban Uganda) and Mbeya
(rural Tanzania). HIV negative eligible women were prospectively
screened twice a week using HIV nucleic acid testing. A positive test
led to entry into an intensive one-month diagnostic verification
phase to definitively establish HIV infection status. Clinical and
laboratory assessments were performed semiweekly. Supportive care
and symptomatic treatment was provided.
Results: Overall, 1197 high-risk volunteers have enrolled to date with
37 cases of AHI identified (31 prior to detectable antibodies). Mean
age at HIV acquisition was 24.4 years (range 1834). Only six
reported unprotected sex with a known HIV positive partner. Crude
incidence was 2.77/100 PY (95% CI:90.87). Of the 37 AHI cases; 14
presented with malaria-like symptoms (all smear negative), 7 flu-like
symptoms while 16 had 12 mild complaints (8) or no symptoms (8).
Overall, AHI cases were evaluated at 302 visits and at least one
symptom was reported in only 75 visits (24.8%). Pregnancy did not
increase the frequency of symptoms but dehydration due to
vomiting resulted in 2 of the 3 hospitalizations observed.
Conclusion: Identification of AHI is feasible in East Africa. Young,
rural, females are most vulnerable. Individuals with clinical syndromes suggestive of malaria, but excluded by microscopy, should
raise index of suspicion for AHI. The majority of cases had few or no
symptoms or brief non-specific symptoms not requiring medical
intervention. Screening protocols based on malaria syndromic
presentation would not identify the majority of AHI cases.
TUPDB0204
Very early initiation of combination antiviral therapy results
in normal levels of markers of immune activation
M. Markowitz, T. Evering, A. Figueroa, K. Rodriguez, M. La Mar,
D. Garmon, V. Sahi and H. Mohri
Aaron Diamond AIDS Research Center, New York, United States
Presenting author email: mmarkowitz@adarc.org
Background: The use of combination antiretroviral therapy (cART)
has resulted in dramatic reductions in HIV-related mortality and
morbidity. Nevertheless, despite sustained suppression of viral
replication there remains evidence of increased levels of immune
activation, particularly in patients initiating treatment during latestage infection. We asked whether early initiation of therapy could
potentially ameliorate this apparent limitation of cART.
Methods: 40 subjects identified as acutely or early HIV-1 infected
were treated with either 3-drug cART (N 14) which included
TDF/FTC, a ritonavir-boosted protease inhibitor (atazanavir or
darunavir) or 5-drugs (N 26) cART as above with raltegravir and
maraviroc. CD38 and HLA-DR expression on CD8 T cells were
determined by flow cytometry at baseline and weeks 48 and 96.
Levels of sCD14 by ELISA were measured at weeks 48 and 96. These
results were compared to values in 13 healthy, HIV-1 uninfected
volunteers.
33
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
Results: A total of 29 subjects, 11 on 3-drugs and 18 on 5-drugs
remained on therapy, suppressed and were available for analysis at
48 weeks. After 96-weeks 25 subjects, 9 on 3-drugs and 16 on 5drugs were similarly analyzed. There are no statistically significant
differences (Mann-Whitney, pB0.05) in markers of cellular or
systemic immune activation between the 3-drug and 5-drug groups
at baseline or after 48 and 96 weeks of therapy. Importantly, the
early treated HIV-infected subjects display comparable levels of
markers of cellular and systemic immune activation when compared
to the healthy HIV-uninfected controls. Markers of Immu . . .
Results: Of 279 HIV/HCV seropositive subjects, 48 were HIV
controllers. HIV controllers were significantly more likely to have
evidence of spontaneous HCV clearance than HIV non-controllers
(58% vs. 38%, p0.01). While HIV controllers were more likely to
have HLAB57 than HIV non-controllers, (33% vs. 10%, pB0.01),
HLAB57 was not significantly associated with HCV clearance among
all participants (39% vs. 55% p0.06), and there was no evidence of
increased prevalence of HCV clearance among HLAB57 vs. HLAB57in HIV controllers (p 0.83). In multivariate analyses adjusted for
HLAB57, age, gender, and race/ethnicity, HCV clearance was
week 48
week 96
Baseline %CD8CD38
%CD8CD38
%CD8CD38
week 48 Mean
week 96 Mean
Group
HLA-DR T cells
HLA-DR T cells
HLA-DR T cells
sCD14 (ng/mL)
sCD14 (ng/mL)
3-drug
49.4
7.4
3.8
1681
1493
5-drug
36.6
7.5
5.2
1558
1449
HIV-uninfected,
7.3
1416
healthy controls
Markers of Immune Activation.
Conclusion: These data suggest that the early initiation of cART may
result in normalization of markers of immune activation that may
provide clinical benefit. These results support well-designed prospective trials to confirm these findings.
significantly more likely in HIV controllers than HIV non-controllers
(APR 1.44; 95% CI 1.042.0; p 0.026).
Conclusion: HIV controllers are more likely to spontaneously clear
HCV than HIV-non-controllers even when controlling for HLAB57
status. Immunologic factors other than HLAB57 must contribute to
the control of HIV and HCV in HIV controllers. Identifying these
factors may support the development of novel treatments for and
effective vaccines against both viruses.
B3 - Elite and viremic controllers
WEAX0105
HLAB57 does not fully explain the ability of HIV controllers
to spontaneously clear hepatitis C virus (HCV) infection
A. Asher1,2, G.-M. Santos1, E.K. Dokubo3, J. Martin4, S. Deeks4,
L. Tobler5, M. Busch5, P. Hunt4 and K. Page1
1
University of California San Francisco, Epidemiology & Biostatistics,
San Francisco, United States. 2University of California San Francisco
School of Nursing, Community Health Systems, San Francisco
United States. 3University of California San Francisco, Center for AIDS
Prevention Studies, San Francisco, United States. 4University of
California San Francisco, Positive Health Program, San Francisco,
United States. 5Blood Systems Research Institute, San Francisco,
United States
Presenting author email: alice.asher@ucsf.edu
Background: HIV controllers, maintaining low plasma HIV RNA levels
( B2000 copies/ml) in the absence of antiretroviral therapy, are also
more likely to spontaneously clear HCV infection. HLAB57, the major
histocompatibility class I gene, is highly enriched in HIV controllers
and is associated with HCV spontaneous clearance. Whether HLAB57
explains the increased prevalence of spontaneous HCV clearance
observed in HIV controllers remains unclear.
Methods: Patients in the Study of the Consequences of Protease
Inhibitor Era (SCOPE) were tested for anti-HCV using enzyme
immunoassay (EIA3) and HCV RNA using discriminatory HCV
transcription-mediated amplification assay (Norvatis† ). We compared the proportion of HIV controllers and HIV non-controllers with
serological evidence of HCV clearance (anti-HCV/RNA ) by chisquare tests and assessed whether HLAB57 status explains the
increased prevalence of HCV clearance in HIV controllers using
adjusted prevalence ratio (APR) with Poisson regression models.
B5 - Disease burden - morbidity/mortality
THAB0304
Trends over time in underlying causes of death in the D:A:D
study from 1999 to 2011
R. Weber1, C. Smith2 and D:A:D Study Group
1
University Hospital, Zurich, Switzerland. 2UCL, Infection and
Population Health, London, United Kingdom
Presenting author email: c.smith@ucl.ac.uk
Background: HIV individuals in care with access to ART may
experience a wider range of non-AIDS-related complications than
previously. It is important to accurately classify causes of death, and
monitor trends over time.
Methods: Individuals from a large prospective cohort collaboration
(D:A:D) were followed starting from 1999 until death, loss-to-followup or February 2011, whichever came first. Underlying causes of
death were attributed based on the Coding of causes of Death
(CoDe) system.
Results: 3,802 deaths occurred in 49,734 individuals followed for
304,695 person-years (rate 12.5/1000 person-years [95% CI 12.1
12.9]). Leading underlying causes were: AIDS-related (29%), nonAIDS-defining malignancies (NADM; 14%), liver disease (LD; 13%),
cardiovascular disease (CVD; 11%), invasive bacterial infection (7%),
drug overdose (3%), accidents (2%), renal disease (1%) and unknown
(7%). Decreases over time occurred in rates of all-cause (17.4/1000
person-years in 19992000 to 8.3 in 20092011), AIDS-related
(5.91.9), LD (2.70.8) and CVD-related (1.8 0.8) mortality.
However, the rate of NADM deaths remained stable (1.51.6).
34
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
Ratio ratio (95% CI) for underlying cause of death over calender time (reference=1999/2000)
2001/2002
2003/2004
2005/2006
2007/2008
20092011
Total deaths
Unadjusted
0.98 (0.851.12)
0.91 (0.791.04)
0.69 (0.600.80)
0.58 (0.500.67)
0.48 (0.410.55)
Adjusteda
1.06 (0.921.23)
1.03 (0.891.18)
0.80 (0.690.93)
0.71 (0.610.83)
0.66 (0.560.77)
AIDS
Unadjusted
0.91 (0.711.16)
0.88 (0.691.12)
0.56 (0.430.72)
0.44 (0.340.57)
0.31 (0.240.42)
Adjusteda
1.11 (0.871.43)
1.20 (0.941.54)
0.86 (0.661.11)
0.82 (0.621.07)
0.85 (0.641.13)
Liver-related
Unadjusted
0.96 (0.671.37)
0.71 (0.501.03)
0.63 (0.430.90)
0.46 (0.320.68)
0.28 (0.180.42)
Adjusteda
1.02 (0.701.47)
0.80 (0.551.17)
0.73 (0.491.07)
0.59 (0.390.88)
0.39 (0.250.61)
Non-AIDS malignancyb
Unadjusted
1.18 (0.741.89)
1.34 (0.842.11)
1.16 (0.731.84)
1.16 (0.731.83)
1.09 (0.691.72)
Adjusted
1.10 (0.681.78)
1.19 (0.751.90)
0.95 (0.591.52)
0.91 (0.571.46)
0.83 (0.521.35)
CVD-related
Unadjusted
1.07 (0.691.66)
0.97 (0.631.51)
0.77 (0.501.20)
0.69 (0.441.07)
0.46 (0.290.74)
Adjusteda
Other/Unknownc
0.99 (0.641.55)
0.84 (0.541.32)
0.62 (0.390.98)
0.51 (0.320.82)
0.31 (0.190.51)
Unadjusted
0.97 (0.761.25)
0.90 (0.701.15)
0.71 (0.550.92)
0.59 (0.450.76)
0.59 (0.450.76)
Adjusteda
1.05 (0.821.36)
1.00 (0.771.29)
0.82 (0.631.07)
0.71 (0.550.93)
0.75 (0.570.99)
Results from Poisson Regression Model. aAdjusted for (fixed) gender, age, ethnicity, riskgroup, HBV status, HCV status, smoking, diabetes,
hypertension, (time-updated) viral load, BMI and CD4 count.
b
Includes lung, prostate, anal, primary liver, GI, breast, uterus, testicular and bladder cancers, leukemias and Hodgkin’s lymphomas. cAlt deaths
that do not meet criteria for other categories.
After accounting for factors including current CD4 count (Table),
there was still evidence of decreases over time in LD and CVD deaths,
but not AIDS-related. The proportion of all deaths attributed to AIDS
(34% in 19992000 to 22% in 20092011), NADM (9%20%) and LD
(16%9%) changed over time.
Conclusion: Underlying causes of death have changed markedly over
the last 12 years. AIDS remains the leading cause. Although there
have been marked reductions over time in AIDS-related deaths, this
effect is removed when accounting for current CD4 and other
factors. NADMs are now the leading non-AIDS cause. Rates of LD and
CVD-related deaths have decreased substantially, even after accounting for the factors listed below, suggesting other improvements in
patient management during the study period. No trends in emerging
causes of unexpected deaths were observed. Collection of specific
causes of deaths is important to allow earlier interventions in HIV
case management.
B7 - HIV testing, including new
algorithms and strategies
THAB0301
Non-adherence to HIV testing guidelines and late HIV
diagnosis is common among U.S. black men who have sex
with men (MSM)
S. Mannheimer1,2, L. Wang3, H.V. Tieu4, C. del Rio5, S. Buchbinder6,
L. Wilton7, S. Glick8, V. Cummings9, K.H. Mayer10 and on behalf of the
HPTN 061 Study Team
1
Harlem Hospital/ Columbia University, Medicine, New York
United States. 2Mailman School of Public Health, Columbia
University, Epidemiology, New York, United States. 3Statistical Center
for HIV/AIDS Research & Prevention (SCHARP), Seattle, United States.
4
New York Blood Center, New York, United States. 5Emory University
Rollins School of Public Health, Department of Global Health, Atlanta,
United States. 6San Francisco Department of Health, HIV Research
Section, San Francisco, United States. 7Binghamton University,
Department of Human Development, Binghamton, United States.
8
The George Washington University School of Public Health and
Health Services, Department of Epidemiology and Biostatistics,
Washington, United States. 9Johns Hopkins University Medical
School, Pathology Department, Baltimore, United States. 10The
Fenway Institute/Harvard Medical School, Boston, United States
Presenting author email: sbm20@columbia.edu
Background: US CDC guidelines recommend at least annual HIV
testing for those at high risk. Nonadherence to testing guidelines and
late diagnosis of infection may contribute to HIV transmission.
Methods: HPTN 061 is a feasibility study of a multi-component HIV
prevention intervention for at-risk black MSM in 6 US cities. At
enrollment, participants were offered HIV testing. Participants
reporting past HIV-uninfected or unknown status at enrollment and
no HIV testing within the prior 12 months were considered
nonadherent to HIV testing guidelines. Participants with newly
diagnosed HIV and CD4 B200 at time of diagnosis were considered
to have late diagnosis. Predictors of nonadherence to testing
guidelines and late diagnosis were analyzed using logistic regression
models and Fisher?s exact tests. HIV test data are from baseline
testing performed at study sites; confirmatory testing is underway.
Results: HPTN 061 enrolled 1553 black MSM. At enrollment, 1384
reported no prior HIV diagnosis, and 1335 (96%) of those participants
agreed to testing; 98% were male, 3% transgender, 100% black,
8% Latino, with a median age of 39 years; 38% reported incomes
below US poverty level, and 67% were unemployed. Among those
tested, 309 (23%) reported no HIV test in prior 12 months; testing
35
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
nonadherence was highest in Atlanta (30%), lowest in DC (18%) and
Boston (17%); 185 (14%) reported never testing prior to enrollment.
Nonadherence to HIV testing guidelines was independently associated with age ]35, (AOR 1.96 [95% CI 1.402.75]), unemployment
(AOR 1.47 [1.052.05]), and living in Atlanta (AOR 1.85 [1.07, 3.21]).
167 (13%) participants had a new HIV diagnosis at enrollment;
median CD4 was 445 at diagnosis. Of 157 (94%) with CD4 data,
28 (18%) had a late HIV diagnosis.
Conclusion: Nonadherence to HIV testing guidelines, undiagnosed
infection and late diagnosis were common, underscoring the need
for additional HIV testing and prevention efforts for this population.
screening was cost-saving were 0.3% and 0.5% at the 3-month and
6-month screening intervals, respectively. Screening with a rapid test
was cost-saving at both 3- and 6-month intervals compared to annual
screening. The incremental cost-effectiveness of 3-month versus 6month screening was $813 per QALY saved.
Conclusion: HIV screening with either conventional or rapid testing
as frequently as every 3 months is cost-saving or very cost-effective.
Reexamination of HIV screening intervals for MSM should be
considered on the basis of the economic evidence.
TUPDB0203
THAB0302
Cost-effectiveness of more frequent HIV screening of men
who have sex with men in the United States
A. Hutchinson, S. Sansom and P. Farnham
Centers for Disease Control and Prevention, Division of HIV/AIDS
Prevention, Atlanta, United States
Presenting author email: ash2@cdc.gov
Background: Recent data showing a high incidence of HIV infection
among men who have sex with men (MSM) who had been tested
during the past year suggest that MSM might benefit from more
frequent HIV screening (e.g., every 3 to 6 months). We assessed the
cost-effectiveness of HIV screening at 3 and 6 month intervals
compared with annual screening.
Methods: We used a published mathematical model of HIV
transmission to evaluate screening intervals for a cohort of 10,000
MSM ages 1464. We incorporated HIV transmissions averted due to
serostatus awareness for each screening interval (e.g. 3, 6, 12
months), as well as HIV testing costs and treatment costs for averted
transmissions. We assumed an HIV incidence of 1.27% for MSM and
conducted threshold analyses on incidence. We assumed conventional testing with a 3rd generation antibody test and 75% receipt of
results. In sensitivity analyses, we investigated the impact of all rapid
testing and 100% receipt of results. We valued each HIV transmission
averted using lifetime treatment costs of $367,134.
Results: Compared to annual screening, conventional HIV testing
every 3 months and 6 months averted 2.04 and 1.36 HIV
transmissions, respectively, and both were cost-saving. The incremental cost-effectiveness of 3-month versus 6-month screening also
was cost-saving. Threshold values for HIV incidence at which
HIV Screening
Every 6
months
Every 3
months
compared to
compared to
compared to
annually
annually
every 6 months
$97,340
$284,574
Every 3 months
$187,233
Costs
HIV Transmissions
1.36
2.04
0.68
Averted
QALYs Saved
HIV Treatment
8.76
13.14
4.38
$500,149
$750,223
$250,074
Cost-saving
Cost-saving
Cost-saving
Costs Saved
Incremental Costeffectiveness
Ratio
Cost-effectiveness of HIV Screening for MSM.
Optimizing a dried blood spot-based pooled RT-PCR
technique for identification of acute HIV infections in
Mochudi, Botswana
R. Davis1, S. Dzoro1, S. Moyo1, S. Gaseitsiwe1,2, R. Musonda1,2,
V. Novitsky1,2 and M. Essex1,2
1
Botswana-Harvard AIDS Institute Partnership, Gaborone, Botswana.
2
Harvard School of Public Health AIDS Initiative, Immunology and
Infectious Diseases, Boston, United States
Presenting author email: rdavis@jhsph.edu
Background: Pooling techniques have been advanced to improve the
cost effectiveness of nucleic acid testing for diagnosis of serologically
undetectable acute HIV infections in resource limited settings.
Previously reported methods have relied on serum samples. The
goal of this study is to develop and apply a novel dried blood spot
(DBS) based RT-PCR pooling technique to facilitate household sample
collection, efficient diagnosis, and treatment-as-prevention strategies in Mochudi, Botswana.
Methods: Laboratory-prepared DBS samples with plasma viral
load 50,000 copies/mL are diluted with HIV negative DBS
samples to generate estimates of sensitivity for pool sizes of 5, 10,
25, 50, and 100 samples. RT-PCR is performed using the Abbott
RealTime HIV-1 assay. This analysis will inform the development of an
acute HIV case detection pooling algorithm to be applied to all
seronegative samples collected as part of a large prevention study
cohort.
Results: Preliminary findings based on 9 HIV positive samples used to
create 90 pools, reflected sensitivities ranging from 27.8% for pools
at 1/100 dilution to 100% for 1/5. We were able to detect the
presence of an HIV positive sample in pools of 10 with a sensitivity of
94.1%. The difference in sensitivity between pool sizes of 25 and 50
was minimal.
Table 1.
Sensitivities of DBS pooled RT-PCR
Mean copies per mL (95% CI)
Pool size
% Sensitivity
38680.96 (28170.00, 49191.91)
19965.30 (15020.37, 24910.23)
5
10
100
94.1
8735.91 (6800.21, 10671.61)
25
71.4
4992.78 (3579.63, 6405.93)
50
70.6
100
27.8
3121.21 (1676, 4566.20)
Conclusion: We have demonstrated the feasibility of using DBS
pooling for acute HIV diagnosis. Because acute HIV infection involves
high viral loads, we can reasonably expect to detect acute cases
50,000 copies/mL in pools of 10 with 94.1% sensitivity. Although
increasing pool size decreases sensitivities, the false negative rate
during the acute window period could be significantly reduced even
36
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
with the use of larger pools. Because secondary HIV transmission in
acute and recent HIV infection may contribute significantly to the
epidemic in Botswana, the potential for a treatment-as-prevention
strategy would be facilitated by screening methods to detect acute
HIV cases.
B8 - Viral load testing, including point of
care diagnostics
WEPDB0103
A field evaluation of HIV-1 RNA viral load in plasma and
dried blood spots using the COBAS Amplicor Analyzer and
the Nucleic Acid Extraction COBAS Ampliprep/Taqman in
Kisumu, Kenya
K. Ouma1, S. Basavaraju2, J. Okonji3, J. Williamson4, L. Mills4 and
C. Zeh4
1
KEMRI-CDC Research and Public Health Collaboration, Kisumu,
Kenya. 2Centers for Disease Control and Prevention, HIV Prevention
Branch, Division of Global HIV/AIDS, Center for Global Health,
Georgia, United States. 3KEMRI-CDC Research and Public Health
Collaboration, HIV Research Laboratory, Kisumu, Kenya. 4Centers for
Disease Control and Prevention, Division of HIV/AIDS Prevention,
Kisumu, Kenya
Presenting author email: kouma@kemricdc.org
Background: In Kenya, HIV-1 viral load (VL) monitoring is commonly
performed with the COBAS Amplicor using plasma specimens, but
interest is growing in transitioning to real-time PCR (RT-PCR),
including the COBAS Ampliprep/COBAS Taqman (CAP/CTM), using
Track B Clinical Science
dried blood spots (DBS). RT-PCR has several advantages including full
automation, lower detection limit, and broader measuring range.
Benefits with DBS include sample collection via finger or heel stick,
low biohazard risk, and specimen transportation under ambient
conditions. Prior to implementation, a direct evaluation of the two
assays using DBS field specimens is required.
Methods: This analysis compares sensitivity, specificity, negative
(NPV) and positive (PPV) predictive values, concordance correlation,
and agreement, as evaluated with Bland Altman analyses, between
HIV-1 VL measurements using paired plasma and DBS specimens
obtained from 512 HIV-1 infected treatment-naive pregnant women
enrolled in the Kisumu Breastfeeding Study, and tested with the
COBAS Amplicor and CAP/CTM assays.
Results: The sensitivity and NPV of VL detection in DBS specimens
were higher with CAP/CTM (sensitivity: 100%, 95% CI: 99.1100.0;
NPV: 100%, 95% CI: 59.0100.0) than COBAS Amplicor (sensitivity:
96.6%, 95% CI: 94.398.1; NPV: 58.8%, 95% CI: 40.775.4), with
comparable PPV; 99.5%, 95% CI: 98.399.9 and 99.6%, 95% CI: 98.6
100.0 for the respective assays. The specificity of VL detection in DBS
specimens was lower with CAP/CTM (77.8%, 95% CI: 40.097.2) than
COBAS Amplicor (95.2%, 95% CI: 76.299.9). Good concordance and
agreement were observed when testing paired plasma and DBS
specimens (Figures 1 and 2).
Conclusion: There was good correlation between DBS and plasma
viral loads as well as between COBAS Amplicor and CAP/CTM.
However, CAP/CTM had a better sensitivity compared to COBAS
Amplicor. Our findings show that DBS may be an alternative sample
type to plasma for viral load measurement, which could increase
access to viral load monitoring in resource limited settings.
Disclaimer: The content and views in this abstract are solely the
responsibility of the authors and do not necessarily represent the
official views of the affiliated organizations, United States Government, or Government of Kenya.
Figure 1. Concordance correlation analyses of HIV-1 viral load quantification among plasma and DBS specimens collected from patients
enrolled in Kisumu Breastfeeding Study and tested with COBAS Amplicor and CAP/CTM. COBAS Amplicor plasma viral loads were used as
reference group for comparison: a) vs. COBAS Amplicor DBS viral loads; b) vs. CAP/CTM plasma viral loads; c) vs. CAP/CTM DBS viral loads
[Correlation plots].
37
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
Figure 2. Bland-Altman analyses to evaluate agreement in HIV-1 viral load quantification among plasma and DBS specimens collected from
patients enrolled in Kisumu Breastfeeding Study and tested with COBAS Amplicor and CAP/CTM. COBAS Amplicor plasma viral loads were
used as reference group for comparison. The difference between the reference and the comparision assay/specimen type were plotted
against the average of the reference group and the comparision assay/specimen type o; a) COBAS Amplicor DBS viral loads; b) CAP/CTM
plasma viral loads; c) CAP/CTM DBS viral loads [Bland-Altman plots].
THPDB0102
Evaluation of the WHO immunologic criteria for
antiretroviral treatment failure among adults on first
line highly active antiretroviral therapy (HAART) in
south India
S. Vallabhaneni1, S. Chandy2, E. Heylen1 and M.L. Ekstrand1,2
1
University of California at San Francisco, Center for AIDS Prevention
Studies, San Francisco, United States. 2St John’s National Academy of
Health Sciences, Medicine, Bangalore, India
Presenting author email: snigdhav@gmail.com
Background: Routine viral load (VL) testing is not available or
recommended for patients on HAART in India. The implications of
not having routine VL testing are not known in this setting.
Methods: As part of a longitudinal adherence study, participants
on first-line HAART in Bangalore, India were monitored every
six months, for 24 months, with CD4 cell count, HIV VL, and
genotype, if VL 1000copies/ml. Participants with virologic failure
(VF) often continued on first line therapy due to local resource
constraints.
We compared the incidence of WHO-defined criteria for immunologic failure (IF) to VF, defined as two consecutive VL 1000
copies/ml or VL10,000 copies/ml for those who had only one VL
available.
Results: Five hundred nine participants were included in the
study (63% male, median age 36, median duration on HAART at
start of study 14 months). Forty (7.8%) experienced VF, 25 (6.1%)
IF and 10 (2.0%) both VF and IF. The sensitivity of immunologic
criteria to detect VF was 20%, specificity 95% and positive-predictive
value 29%. Of the 40 participants with VF only, 18 developed
new thymidine analogue mutations over the follow-up period
during which they continued on first line therapy; 11 of 18
developed high- level NRTI resistance, which would preclude
subsequent tenofovir use. In addition, six participants developed
NNRTI mutations, which confer genotypic resistance to etravirine and
rilpivirine.
Conclusion: WHO IF criteria have low sensitivity for detecting VF and
presence of IF poorly predicts VF. Relying on CD4 count data alone
would lead a substantial number of unnecessary switches to secondline therapy. A notable proportion of patients would be continued on
first line therapy that they are already failing, jeopardizing future
HAART options. Universal access to VL monitoring would avoid costly
switches to second line therapy and preserve future therapeutic
options.
B9 - Drug resistance testing
TUAB0304
High levels of drug resistance after failure of first-line
antiretroviral therapy in rural South Africa: impact on
standardised second-line regimens
J. Manasa1, N. McGrath1,2, R. Lessells1,3, A. Skingsley1, M.-L. Newell1
and T. de Oliveira1
1
University of KwaZulu-Natal, Africa Centre for Health and Population
Studies, Somkhele, South Africa. 2London School of Hygiene and
Tropical Medicine, Infectious Disease Epidemiology, London,
38
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
United Kingdom. 3London School of Hygiene and Tropical Medicine,
Clinical Research, London, United Kingdom
Presenting author email: jmanasa@gmail.com
Background: Rapid scale-up of antiretroviral therapy (ART) in
Southern Africa has put enormous strain on health systems.
Information about acquired drug resistance in treated individuals is
important to monitor quality of programmes and to ensure that ART
policies remain appropriate. The majority of resistance data so far
have come from urban, hospital-based programmes; limited data
have been reported from rural treatment programmes.
Methods: Adult ( ]16 years) HIV-infected individuals with virological
failure (2 VL1000 copies/ml) on first-line NNRTI-based ART were
enrolled from all 17 primary health care clinics of the Hlabisa ART
Programme. Genotypic resistance testing was performed using the
in-house SATuRN/Life Technologies system. Sequences were analysed
and genotypic susceptibility scores (GSS) were calculated using
RegaDB and Stanford HIVDB 6.0.5 algorithms.
Results: 187 adults enrolled between Dec 2010 and Dec 2011;
median age 37 years (IQR 3145); 70% female. Median time on ART
41 months (IQR 3153); median time on failing regimen 30 months
(IQR 2042). 120 (64%) had never achieved full virological suppression (VL 550 copies/ml). 160 (86%) individuals had ]1 drug
resistance mutation; 149 (80%) and 153 (82%) respectively had NRTI
and NNRTI mutations. 72 (38%) had at least one thymidine analogue
mutation (TAM) and 32 (17%) had ]3 TAMs. 14 (7%) had other NRTI
mutations that might impact on second-line therapy (K65R-12 (6%);
Q151M-3 (2%)). The standard second-line regimen was substantially
compromised (defined as GSS 51.5) in 33 (18%) individuals.
Conclusion: There are high levels of acquired drug resistance
associated with prolonged virological failure in this rural primary
health care programme. Standard second-line regimens would be
significantly compromised in almost one in five adults. This suggests
a role for genotypic resistance testing in routine care but, more
importantly, it highlights the need for increased attention to quality of
care and adherence to virological monitoring guidelines.
THPDB0101
Accumulation of protease mutations among patients on
non-suppressive 2nd-line ART in Nigeria
H. Rawizza1, B. Chaplin2, S. Meloni2, P. Okonkwo3, P. Kanki2 and the
APIN PEPFAR Team
1
Brigham & Women’s Hospital, Infectious Disease, Boston, United
States. 2Harvard School of Public Health, Immunology and Infectious
Disease, Boston, United States. 3AIDS Prevention Initiative In Nigeria
(APIN), Abuja, Nigeria
Presenting author email: hrawizza@hsph.harvard.edu
Background: In assessing the cost-effectiveness of CD4 versus viral
load (VL) monitoring strategies, the ‘‘resistance cost’’ associated
with delays in identifying non-suppression must be considered, and
would likely favor a VL strategy. Here we examined the extent of
protease (PR) mutation accumulation according to duration of 2nd-line
(2L) failure.
Methods: Since 2004, the Harvard PEPFAR/APIN Program has
provided ART to over 85,000 people in Nigeria. Approximately 8%
of patients have received protease inhibitor (PI)-based 2L therapy
(mostly LPV/r). A subset of patients with VL failure, defined as 2
consecutive VLs 1000cpm after ]6 months on 2L, underwent
genotypic resistance testing. Accumulation of PR mutations according to time on failing regimen was determined.
Results: Of 6714 patients who received PI-based ART, 661 (9.8%) met
virologic failure criteria. Genotypes were performed on 53 samples
(median CD4 183; VL 30150 at 2L failure).
Time on Failing 2nd-line Regimen
0 12 months (n 15)
13 24 months (n27)
Age (years), median (IQR)
43 (3447)
40 (3443)
42 (3251)
42 (3346)
% Female
33%
48%
55%
45%
Characteristic
24 months (n11)
Total (n53)
# ARVs previously used, median (range)
6 (47)
6 (48)
6 (59)
6 (49)
Duration on 1L (months), median (IQR)
Duration on 2L (months)
23 (1937)
12 (820)
28 (1637)
20 (1822)
16 (1423)
36 (3450)
24 (1535)
20 (1634)
8 (611)
18 (1620)
34 (3240)
17 (1222)
96 (87100)
91 (78100)
92 (84100)
Time Failing 2L Regimen (months)
2L Adherence (%), median (IQR)
89 (7998)
Characteristics of Patients Failing 2L ART.
Time on Failing 2L Regimen
Protease Resistance
0 12 months (n15) 13 24 months (n27)
24 months (n 11) Total (n53)
Total # PR mutations, median (IQR)
3 (15)
2 (05)
6 (06.5)
3 (05)
Major PR mutations
Minor PR mutations
0 (01.5)
2 (0.53.5)
0 (03)
2 (02)
3 (04)
2 (03)
1 (03)
2 (02)
23 (43%)
High- or Intermediate-level PI Resistance, # (%)
Lopinavir (LPV/r) and Atazanavir (ATV/r)
4 (27%)
12 (44%)
7 (64%)
Darunavir (DRV/r)
0 (0%)
4 (15%)
1 (9%)
5 (9%)
# PR mutations/6 mo. on Failing 2L, median (IQR)
2.7 (0.53.7)
0.9 (01.8)
0.8 (01.1)
1.1 (02.3)
# PR mutations/6 mo. on Failing 2L (No PR
3.4 (2.64)
1.4 (0.82.3)
1.1 (0.91.2)
1.8 (1.12.8)
mutations excluded)
Protease Mutation Accumulation by Time Failing.
39
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
Patients on non-suppressive 2L therapy for 512 months prior to
genotype testing had a median of 3 (IQR, 15) International AIDS
Society (IAS) PR mutations, compared with 6 (IQR, 06.5) among
patients failing for 24 months. Patients developed a median of 1.1
(IQR, 02.3) IAS PR mutations per 6 months on failing 2L therapy. In
30% of failing patients no PR mutations were present, suggesting
non-adherence; when these patients were excluded, the median
number of IAS PR mutations/6 months increased to 1.8 (IQR, 1.1
2.8). For patients failing 24 months, high- or intermediate-level
resistance to LPV/r and ATV/r was present in 64%, with 9% to
DRV/r.
Conclusion: This is the first report assessing the impact of duration of
non-suppressive 2L therapy on the accumulation of PR resistance in a
resource-limited setting. This information provides insight into the
‘‘resistance cost’’ associated with failing to switch non-suppressive 2L
regimens, and highlights the issue of 3rd-line access.
1999 to 2011. To be included in this evaluation, a person had
consecutive VL B200 copies/mL with consecutive CD4 counts ]200
cells/mL.
Results: Of the 906 persons who met our criteria, 32 subsequently
experienced a CD4 count B200 cells/mL. Within the year prior to
that CD4 count B200 cells/mL, 27/32 had a confirmed CD4 count of
200249 cells/mL, and only 5/32 had a confirmed count of 250349
cells/mL. No one who had a confirmed CD4 count ]350 cells/mL and
a VL that remained B200 copies/mL, ever experienced a CD4 count
drop below 200 cells/mL.
Conclusion: For an individual who has viral suppression ofB200
copies/mL and a confirmed CD4 count between 250 and 349 cells/
mL, CD4 cell count monitoring may be necessary less frequently than
34 times/year. After a confirmed CD4 count ]350 cells/mL, annual
measurements appear safe for persons who maintain viral suppression, and additional data may support even less frequent CD4 cell
count monitoring.
B11 - CD4 testing, including point of care
diagnostics
B12 - Opportunistic infections (excluding
tuberculosis)
WEPDB0101
MOAB0102
Frequent CD4 cell count monitoring is not necessary for
persons with counts ]350 cells/ml and viral suppression
H. Gale1, S. Gitterman1, F. Gordin1,2, D. Benator1,2 and V. Kan1,2
1
Veterans Affairs Medical Center, Infectious Diseases Section,
Washington, United States. 2George Washington University Medical
Center, Division of Infectious Diseases, Washington, United States
Presenting author email: howard.gale@va.gov
Background: In the USA, CD4 cell counts and HIV-1 viral load (VL)
have been tested concomitantly 24 times/year for persons receiving antiretroviral therapy (ART). With the advancement of effective
HIV care, many individuals now have viral suppression and higher
CD4 cell counts. After therapy is initiated, the CD4 cell count is used
to monitor the need for prophylaxis against opportunistic infections
and immunologic response to ART. We assessed whether CD4 cell
counts may be performed less frequently after viral suppression
of B200 copies/mL in persons with CD4 counts above the 200 cells/
mL threshold for opportunistic infections.
Methods: We examined approximately 25,000 paired VL and CD4
cell counts from the 1,720 individuals seen in our clinic during
Table 1.
Summary of persons with & without CD4 B 200
CD4 count
Persons with sustained
Persons experiencing a
range
CD4 count ]200 cells/
CD4 count B200 cells/
(cells/mL)
mL N874
mL N32
200249
127
27
250299
300349
107
107
3
2
]350
533
0
Summary of eventual CD4 cell counts during viral suppression of
B200 copies/mL, 19992011. The number of individuals in each
CD4 cell count stratum is given. CD4 cell count range refers to
the initial count for Persons with sustained CD4 cell counts ]200
cells/mL and to the highest count in the year prior for Persons
experiencing a CD4 count B200 cells/mL.
Cost benefit of integrating cryptococcal antigen screening
and preemptive treatment into routine HIV care
D. Meya1,2, R. Rajasingham1, M. Rolfes2, K. Birkenkamp2 and
D. Boulware2
1
Infectious Diseases Institute - Makerere University, Research,
Kampala, Uganda. 2Division of Infectious Diseases and International
Medicine, University of Minnesota, Department of Medicine,
Minneapolis, United States
Presenting author email: radha.rajasingham@gmail.com
Background: Cryptococcal meningitis (CM) is a leading cause of
death in AIDS patients in sub-Saharan Africa. Cryptococcal antigen
(CRAG) can be detected weeks before symptom onset, and those
who are asymptomatic but CRAG have a high risk of subsequent
CM and mortality. A new CRAG point-of-care immunochromatographic lateral flow assay (LFA) is available that is remarkably easy to
administer without laboratory infrastructure or expertise and has
excellent sensitivity and specificity.
Methods: We assessed the cost-benefit of targeted CRAG screening
for patients with CD4B100 cells/mcL using the LFA ($2.50 total/
screen) and preemptive fluconazole therapy in persons entering into
HIV care in sub-Saharan Africa.
Results: Based on published CRAG prevalence rates of 8.8%
among HIV-infected persons with CD4B100 cells/mcL in Kampala,
Uganda, the cost of detecting one person with asymptomatic
antigenemia with the LFA would be $28.37, and the cost of saving
one life would be $39.73 (95% CI: $28 to $60). Assuming an average
increase in life expectancy of 18 years for a 30 year old Ugandan
initiating antiretroviral therapy (ART) with a CD4 count B100 cells/
mcL, this equates to $1.57 per quality-adjusted life year (QALY)
saved. Based on CRAG prevalence of between 412% in subSaharan Africa, the cost to save one life ranges from $37$114 in
persons with CD4B100 cells/mcL. In contrast, the cost of hospitalization and treatment with amphotericin-based therapy for symptomatic CM is$414 per episode in Uganda. Thus, for the cost of
treating a single episode of CM, one could screen 165 persons using
the LFA screening protocol, which remains cost-effective to 1%
CRAG prevalence.
Conclusion: Screening and preemptive fluconazole therapy is costsaving to healthcare systems and should be integrated into routine
40
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
with humidity (P B0.001) in univariate and multivariate analyses.
Incorporating hypothetical exposure-to-admission delays revealed
a significant association with incubation periods of up to three
weeks (P for incubation of 1 week 0.0008, 2 weeks0.002,
3 weeks 0.002).
Conclusion: Our findings suggest that humidity is the most important
determinant of P. marneffei admissions, and that P. marneffei has an
incubation period of 13 weeks. Based on these results, we
postulate that humidity may drive reported P. marneffei incidence,
perhaps by promoting expansion of the environmental reservoir or
by facilitating fungal growth and/or survival in the environment.
Our findings provide clues to the environmental reservoir and
transmission of P. marneffei, which may direct the design and timing
of much-needed prevention strategies for people living with HIV/
AIDS in Asia.
HIV care, targeting those with CD4 counts B100 cells/mcL. Better
understanding of the implementation science is needed to determine how best to scale up CRAG screening.
MOAB0103
Determinants of penicilliosis seasonality in Ho Chi Minh
City, Vietnam
P. Bulterys1, T. Le2,3, V.M. Quang4, K. Nelson5 and J. Lloyd-Smith6,7
1
University of California Los Angeles, David Geffen School of
Medicine, Medical Scientist Training Program, Los Angeles, United
States. 2Oxford University Clinical Research Unit, Wellcome Trust
Major Overseas Program, Ho Chi Minh City, Viet Nam. 3University of
Hawaii at Manoa, Hawaii Center for AIDS, Honolulu, United States.
4
Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam. 5Johns
Hopkins Bloomberg School of Public Health, Department of
Epidemiology, Baltimore, United States. 6University of California Los
Angeles, Department of Ecology and Evolutionary Biology, Los
Angeles, United States. 7National Institutes of Health, Fogarty
International Center, Bethesda, United States
Presenting author email: pbulterys@mednet.ucla.edu
B13 - Tuberculosis (TB)
MOAB0301
Background: Penicillium marneffei is an emerging dimorphic
mycosis endemic in South and Southeast Asia, and a leading cause
of mortality among HIV-infected people in the region. Factors
governing the seasonal incidence of P. marneffei infection have yet
to be identified, and may yield critical insights into possible
reservoirs or modes of transmission. We used P. marneffei incidence
data from Ho Chi Minh City (HCMC), Vietnam from 20042010, as
well as high-resolution weather data, to identify climactic factors
that could account for the observed seasonality of P. marneffei
infection.
Methods: This study included all P. marneffei, Cryptococcus
neoformans, and HIV-related admissions to the Hospital for Tropical
Disease (HTD) in HCMC from 20042010, as well as temperature,
humidity, wind, and precipitation data for the corresponding period.
We used logistic regression modeling to identify factors significantly
associated with P. marneffei and C. neoformans admissions. We
also estimated the P. marneffei incubation period by incorporating
different exposure-to-admission delays in our models.
Results: This analysis included 719 HIV-infected patients presenting
with penicilliosis. P. marneffei admissions were closely associated
Relationship between weight, efavirenz (EFV)
concentrations and virologic suppression in HIV patients
on rifampin (RIF)-based TB treatment in the ACTG 5221
STRIDE study
A.F. Luetkemeyer1, S.L. Rosenkranz2, D. Lu2, P.S. Lizak3, P. Ive4,
S. Swindells5, C.A. Benson6, B. Grinsztejn7, I.M. Sanne4, D.V. Havlir1,
F. Aweeka3 and Adult AIDS Clinical Trials Group A5221
1
San Francisco General Hospital, University of California at
San Francisco, Division of HIV/AIDS, San Francisco, United States.
2
Statistical Data Analysis Center, Harvard School of Public Health,
Boston, United States. 3San Francisco General Hospital, University of
California at San Francisco, Department of Clinical Pharmacy
San Francisco, United States. 4University of Witswatersrand, Clinical
HIV Research Unit, Johannesburg, South Africa. 5University of
Nebraska at Omaha, Infectious Diseases, Omaha, United States.
6
University of California at San Diego (UCSD), Division of Infectious
Diseases, San Diego, United States. 7Fundação Oswaldo Cruz, STD/
AIDS Clinical Research Laboratory, Rio de Janeiro, Brazil
Presenting author email: aluetkemeyer@php.ucsf.edu
Table 1.
Weight (kg)
B50
]50
p-value
B60
]60
p-value*
total
p-value**
0.07
EFV Cmin ON RIF
2.08 (1.33, 4.33) 1.86 (1.18, 3.64)
0.09
2.02 (1.29, 4.09) 1.68 (1.07, 3.06)
0.02
1.87 (1.18, 3.66)
EFV Cmin ON RIF
2.05 (1.29, 3.26) 1.68 (1.22, 2.39)
0.04
1.89 (1.29, 2.74) 1.60 (1.21, 2.29)
0.14
1.79 (1.23, 2.62)
% Any EFV B1
27.2%
27.4%
0.95
26.2%
30.8%
0.32
27.3%
mg/ml, ON RIF
% Any EFV B1
(21.6, 32.8)
25.4%
(23.4, 31.5)
26.7%
0.79
(22.5, 29.9)
25.7%
(23.7, 37.9)
28.0%
0.06
(23.4, 31.2)
26.2%
mg/ml, OFF RIF
(19.0, 31.9)
(21.9, 31.5)
(21.3, 30.1)
(20.2, 35.7)
79.8%
84.2%
80.6%
88.8%
(74.8, 84.8)
(80.9, 87.6)
(77.3, 84.0)
(84.1, 93. 4)
% HIV RNA B400
at wk 48, ON
0.13
0.72
(21.7, 30.8)
0.01
82.7%
(79.9, 85.4)
EFV
EFV Cmin m/ml: median (IQR), Proportion (95% CI).
*For comparison of EFV Cmin, by weight, Wilcoxon-rank sum p-value was used.
For comparison of percent, chi-squared pvalue wos used.
**p-value for comparison of Cmin on-RIF (n 505) and off RIF (n362) Wilcoxon-rank sum p-value was used, and % EFV B1 on-RIF and off-RIF,
chi-square dp-value was used.
41
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
Background: RIF upregulates CYP 450 isoenzymes and can lower EFV
exposure, particularly if weight ]50 kg, However, clinical data have
not shown reduced HIV virologic suppression with 600 mg EFVRIF.
We conducted a nested PK study to evaluate EFV concentrations and
virologic suppression in A5221 patients on EFV(600 mg) and RIFbased TB treatment.
Methods: EFV Cmin was measured using HPLC (LLQ 0.1 mg /ml)
in samples from 2028 hours post-dose at weeks 4,8,16,24 on-RIF,
and weeks 4,8 off-RIF, in those with no missed doses for 3 days.
Two-sided Wilcoxon rank-sum tests, logistic regression and Fisher’s
Exact tests were evaluated at 5% Type I error rate.
Results: 780 patients from 4 continents received EFV, 543 provided
]1 EFV measurement. Median(IQR) weight was 52.8 kg(48.0,59.5),
BMI 19.4kg/m2(17.5,21.6), age 34, 63% male, race Black(74%),
Hispanic(20%), non-Hispanic White(5%), Asian(1%). Weight ]60 kg
on-RIF was associated with lower EFV Cmin, as was weight]50 offRIF(Table). Weight ]50 and]60 were not associated with less
frequent HIV virologic suppression (HIV RNA B400 copies/ml) at
week 48. In multivariate models, neither higher weight nor BMI was
associated with lower likelihood of virologic suppression. There was
no significant difference in the proportion with any subtherapeutic
Cmin ( B1) on-RIF(27.3%) vs. off-RIF(26.2%) Median Cmin was higher
on-RIF vs. off-RIF in Blacks(2.0 vs 1.6. pB0.01) but did not differ in
Whites(1.3 vs 1.6, p 0.5), Hispanics (1.7 vs. 1.9, p0.3), and
Asians(2.0 vs 1.6, p 1.0). On-RIF, Blacks had more supratherapeutic
Cmin ( 4) compared to Whites(22.9% vs 3.9%;p 0.002).
Conclusion: Overall, RIFcoadministration was not associated with
lower EFV trough concentrations; patients weighing ]50 or ]60 kg
had lower EFV Cmin, but there was no association with subtherapeutic Cmin nor virologic suppression. These data from a multinational, predominantly non-White population do not support
guidelines for weight-based dosing of EFV with RIF.
Results: Of 4,128 participants enrolled with known HIV status and
who received ]1 dose of study therapy, 393 were HIV : 207 in the
3HP and 186 in the 9H arm. In the MITT analysis (enrolled
participants who were eligible), 178/201 (89%) HIV persons
completed 3HP vs. 125/193 (65%) on 9H (PB 0.001). The proportion
of participants with a serious adverse event (SAE), ]1 AE, or
hepatotoxicity was lower in 3HP than 9H (4 vs. 11%; P 0.006; 22 vs.
40%; P0.004; 2 vs. 6%; P 0.03). Compared to 1,888 HIV-negative
participants treated with 3HP, HIV persons were less likely
to permanently discontinue treatment for any reason (11 vs. 20%;
P B0.001) or to have possible drug hypersensitivity (1 vs. 5%;
P 0.003), and there were no significant differences in the
proportion with SAE, ]1 AE, or hepatotoxicity.
Conclusion: Among HIV persons not receiving ART, 3HP was better
tolerated and had higher treatment completion rates than 9H for
treatment of latent M. tuberculosis infection.
MOAB0302
Background: HIV and TB are threats to pregnant women and infants.
Treatment with rifampin can reduce ART concentrations and increase
risk of treatment failure and vertical transmission. We describe the
pharmacokinetics (PK) and pharmacodynamics of EFV among
pregnant HIV-infected women.
Methods: Prospective cohort of HIV-infected pregnant women with
and without TB in Soweto. Women taking ART with EFV 600 mg had
PK sampling at 37 weeks’ gestation or at delivery and then six weeks
post-partum. EFV concentrations were measured in cord blood at
delivery and in infants at 7 days. Post-hoc Bayesian estimates of PK
parameters from nonlinear mixed-effects modeling with allometric
scaling are reported.
Results: Among 41 HIV-infected pregnant women taking EFV ART, 19
received rifampin (TB/HIV) and 22 ART alone. Median age and weight
were 29 years and 70 kg. For 35 women with pre-/peripartum
EFV PK, median (IQR) estimated EFV trough (Cmin) was 1.31 (0.84,
1.86)mg/L, apparent oral clearance (CL/F) 13.62 (10.67, 18.44)L/h,
and volume of distribution (Vd/F) 516 (440, 591)L. 31% had Cmin
B1 mg/L. Predicted median Cmin by CYP2B6 516/983 metabolizer
genotype was: 1.04 (extensive), 1.34 (intermediate), and 4.36 mg/L
(slow). TB treatment did not significantly affect EFV Cmin (1.28 v
1.42mg/L). 5/26 women tested at delivery had viral load 20
copies/mL (one had TB/HIV). Median cord blood EFV concentration
was 1.09 (0.46, 2.38)mg/L. EFV concentrations were BLQ in 6/24 cord
blood and 25/30 infant 7-day samples; both correlated with maternal
concentrations. 0/35 infants were HIV-infected at 6 weeks. In
mothers 6 weeks postpartum, median EFV Cmin was 1.75mg/L, CL/
F 10.79L/h, and Vd/F 433L; 30% had Cmin B1mg/L.
Conclusion: TB treatment did not significantly reduce EFV Cmin, but
pregnancy may lower EFV concentrations. Although 30% of
Tolerability among HIV-positive persons of three months of
once-weekly rifapentineINH (3HP) versus 9 months of
daily INH (9H) for treatment of latent tuberculosis infection:
the PREVENT TB Study (TBTC Study 26/ACTG 5259)
T. Sterling1, C. Benson2, N. Shang3, J. Miro4, B. Grinsztejn5,
R. Chaisson6, A. Lucchetti7, J. Sanchez8, N. Scott3, E. Villarino3 and
AIDS Clinical Trials Group, Tuberculosis Trials Consortium
1
Vanderbilt University, Nashville, United States. 2University of
California-San Diego (UCSD), San Diego, United States. 3Centers for
Disease Control & Prevention, Atlanta, United States. 4Agencia de
Salut Publica, Barcelona, Spain. 5Fundaao Oswaldo Cruz, IPEC
Evandro Chagas, Rio de Janeiro, Brazil. 6Johns Hopkins University,
Baltimore, United States. 7Inmensa, Lima, Peru. 8Impacta, Lima, Peru
Presenting author email: timothy.sterling@vanderbilt.edu
Background: HIV is the strongest risk factor for progressing from
latent M. tuberculosis infection to tuberculosis (TB). 9 months of
daily self-administered INH (9H) is efficacious but has low completion
rates and may cause hepatotoxicity. PREVENT TB demonstrated that
3 months of once-weekly rifapentine 900 mgINH 900 mg under
direct observation (3HP) was at least as effective as 9H, but only 3%
of the participants were HIV, so enrollment of HIV persons was
extended to adequately assess tolerability.
Methods: HIV persons ]2 years old who were either tuberculin
skin test positive or close contacts of TB cases were randomized to
3HP or 9H. Persons could not receive antiretroviral therapy (ART) for
90 days after enrollment. Participants were enrolled from the U.S.,
Brazil, Spain, Peru, and Canada between June 2001 and December
2010. Follow-up for TB continues through 2013.
MOAB0303
Efavirenz (EFV) concentrations in pregnant women taking
EFV-based antiretroviral therapy (ART) with and without
rifampin-containing tuberculosis (TB) treatment:
the TSHEPISO Study Team
H. McIlleron1, N. Martinson2,3, P. Denti1, F. Mashabela2, J. Hunt3,
S. Shembe2, J. Hull4, D.W. Haas5, R. Msandiwa2, S. Cohn3,
R. Chaisson3, K.E. Dooley3 and TSHEPISO Study Team
1
University of Cape Town, Cape Town, South Africa. 2Perinatal HIV
Research Unit (PHRU), University of the Witwatersrand, Soweto,
South Africa. 3Johns Hopkins University School of Medicine,
Baltimore, United States. 4Chris Hani Baragwanath Hospital and
University of the Witwatersrand, Department of Obstetrics, Soweto,
South Africa. 5Vanderbilt University, Nashville, United States
Presenting author email: kdooley1@jhmi.edu
42
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
pregnant women had EFV Cmin B 1mg/L at standard doses, EFVcontaining ART suppressed viral load in most and there were no
vertical transmissions.
MOAB0304
Pharmacokinetic interaction between the investigational
anti-tuberculosis agent TMC207 and rifampicin or rifapentin
D. Everitt1, H. Winter2 and E. Egizi1
1
TB Alliance, New York, United States. 2University of Otago, Dunedin,
New Zealand
Presenting author email: dan.everitt@tballiance.org
Background: TMC207 (bedaquiline) (B) is a diarylquinoline in Phase 2
development to treat drug-sensitive and drug-resistant tuberculosis.
It is being evaluated in novel combination regimens with an aim to
minimize adverse interactions with antiretroviral therapy (ART). This
study investigated the effect of enzyme inducers rifapentine (P) or
rifampicin (R) on TMC207 pharmacokinetics.
Methods: This was a 2-period, single-sequence drug interaction
study performed in 2 groups of healthy subjects. Period 1 examined
the PK of B and its M2 metabolite after a single 400 mg dose of B.
Period 2 examined the effects of repeated doses of either P or R on
the PK of B and M2. Subjects took P 600 mg (Group 1) or R 600 mg
(Group 2) q.d. for 22 days. A single 400 mg dose of B was
administered on Study Day 10 of period 2 followed by PK sampling
for 14 days.
Results: 32 subjects were enrolled and 29 completed; B, alone, and
in combination with P or R, was generally well tolerated. P and R
both reduced the Cmax and AUC of B greater than M2.
Background: PA-824 (Pa) and bedaquiline (B) (TMC) are novel
compounds in phase 2 development with established Early Bactericidal Activity (EBA) over 14 days. The study presented is an EBA
study that evaluated these drugs alone or in combination with each
other and with moxifloxacin (M) and pyrazinamide (Z) to identify a
regimen with the potential to shorten treatment of TB in patients
without the use of rifamycins or other drugs that interact adversely
with antiretroviral Therapy (ART).
Methods: 83 participants enrolled (26% F, 74% M, including 6 HIV)
as five cohorts of 15 TB patients, each who received daily dosages of
B alone, B with Z, B with Pa, Pa with Z and Pa with M and Z. A cohort
of 8 patients received daily standard TB treatment (isoniazid,
rifampin, Z and ethambutol: HRZE) as a control for the EBA
quantitative mycobacteriology. The primary efficacy endpoint was
the rate of change in number of colony forming units (CFU) of
Mycobacterium tuberculosis per ml of sputum incubated on
agar plates from serial sputum collections over the period Day 0
to Day 14.
Results: All cohorts had decreases in logCFU counts/ml of sputum
from Days 0 to 14 that ranged from 1.22.7 over 14 days. While Z
potentiated the activity of both B and Pa and compared favorably
with the HRZE standard regimen, the cohort with the combination
Pa-M-Z had numerically the greatest effect on CFU reduction.
Conclusion: The combination regimen of Pa-M-Z has potent
bactericidal activity over 14 days in patients with pulmonary TB
and has the potential to treat both Drug Sensitive- and Drug
Resistant-TB (contains no INH or rifampicin) without adverse clinical
interactions with ART. This regimen has been taken into an 8 week
trial to treat DS- and DR-TB in patients with and without HIV
infection.
Geometric LS Means of
Bedaquiline
Confidence Intervals
Treatment Group
Rifapentine Group 1
Parameter
Cmax
AUC(01)
Rifampicin Group 2
Cmax
AUC(01)
With Inducer
Alone
Mean Ratio
90% Confidence
2077
3339
62.2
(53.4, 72.5)
27612
64531
42.3
(37.8, 48.5)
2240
3718
60.2
(52.0, 69.8)
25314
61209
41.4
(37.7, 45.4)
Results Table.
Conclusion: Both P and R reduce the Cmax and AUC of single doses of
B by approximately 58%. Future regimens with B to treat TB should
avoid the inclusion of P or R. The development of B with R sparing
regimens is ongoing.
MOAB0305
A phase 2 trial of novel anti-tuberculosis regimens with
increased efficacy and low potential to interact adversely
with antiretroviral therapy
D. Everitt1, S. Murray2, A. Diacon3, R. Dawson4, J. Hutchings4,
C. Van Niekerk5, E. Egizi2 and P. Becker6
1
TB Alliance, Research & Development, New York, United States. 2TB
Alliance, New York, United States. 3Stellenbosch University, Cape
Town, South Africa. 4University of Cape Town, Cape Town, South
Africa. 5TB Alliance, Pretoria, South Africa. 6Medical Research Council
of South Africa, Johannesburg, South Africa
Presenting author email: stephen.murray@tballiance.org
THAB0102
Impact of HIV on early MDR-TB treatment outcomes in
Botswana
J. Hafkin1, C. Modongo2, C. Newcomb1, E. Lowenthal3,
R.R. MacGregor1, A. Steenhoff2,3, H. Friedman1 and G. Bisson1
1
University of Pennsylvania, Philadelphia, United States. 2Botswana
UPenn Partnership, Gaborone, Botswana. 3Children’s Hospital of
Philadelphia, Philadelphia, United States
Presenting author email: hafkin@gmail.com
Background: The impact of HIV on MDR-TB treatment outcomes in
sub-Saharan Africa remains unclear where extensive rollout of highly
active antiretroviral therapy (HAART) has occurred. We therefore
compared the time to initial culture conversion among patients with
and without HIV infection in a setting of individualized, ambulatory
MDR-TB care in Botswana.
Methods: We performed a prospective cohort study of MDRTB patients receiving ambulatory care at two public clinics in
Botswana. The time to culture conversion and proportion converting
43
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2011, 15 (Suppl 3)
Track B Clinical Science
were compared by HIV status using Cox proportional hazard
ratios (HRs).
Results: 40 HIV-infected and 30 HIV-uninfected patients with MDRTB and follow up cultures were identified. The median CD4Tlymphocyte count of those with HIV was 215 cells/mm3 (IQR 129
347), and 36 (90%) were on HAART. 85% of HIV-infected and 83% of
HIV-uninfected achieved culture clearance. The median time to initial
culture conversion was 78 days (IQR 42186) for HIV-infected and 95
days (IQR 70133)for HIV-uninfected individuals [log rank p 0.62;
unadjusted HR0.9 (95% CI: 0.5 to 1.5)]. Adjusting for age, gender,
TB treatment history and number of active antitubercular drugs used
did not change this result [adjusted HR 0.8 (95% CI: 0.4 to 1.4)].
Toxicity was frequent in all subjects: ototoxicity occurred in 53% and
70%, neuropathy in 40% and 10%, and nephropathy in 25% and 7%
of HIV-infected and uninfected patients, respectively. Neuropathy
(p 0.005) & nephropathy (p0.044) were significantly associated
with HIV infection.
Conclusion: We found no difference in the proportion or time to
initial sputum culture conversion between an HIV-infected and noninfected cohort of MDR-TB patients in Botswana. These results
suggest that microbiologic outcomes among those with HIV can be
comparable to those without HIV in similar settings with access to
individualized TB treatment and HAART.
THAB0103
compared to determine the number of excess cases detected by
Xpert. Cost per excess case detected was calculated.
Results: 436 clinical samples were tested using Xpert. 417 were
sputum samples and 19 extrapulmonary samples. Of 64 samples
which tested positive by Xpert, 61 were sputum samples and 3
extrapulmonary samples. Corresponding smear results were available for 58 sputum samples. Table 1 shows a comparsion of Xpert
and smear results.
Xpert positive (Total
58 with smears
available)
% of total positive
Background: Tuberculosis, the leading cause of death among HIV
patients, is difficult to diagnose with smear microscopy. Xpert MTB/
RIF, a near point-of-care, fully automated, nucleic acid amplification
test for TB and for the detection of rifampin resistance, has been
endorsed by WHO. Xpert has increased sensitivity compared with
smear microscopy; however its cost-effectiveness and affordability in
resource limited settings is still controversial.
Methods: Between August and December 2011, Partners in Hope
integrated Xpert MTB/RIF alongside fluorescence microscopy for TB
evaluation.
Attribute
Microscope
of
type
Laboratory
Technician
experience
and
expertise
Partners in Fluoroscence Advanced
Hope
Standard
Conventional Usually
Malawian
limited
AFB
laboratory
Laboratory
staff
workload
Quality
of AFB
Microscopy
Usually
Good
manageable
Usually
Usually
overburdened poor
Attributes of study laboratory and standard lab.
All HIV-TB suspects were evaluated with spot AFB smear, morning
Xpert and another spot smear. Patients were classified as smearpositive, indeterminate (only one scanty smear) or smear-negative
based on Malawi TB Guidelines. Smear and Xpert results were
AFB smear
indeterminate
AFB smear
negative
35
15
8
60%
26%
14%
Comparsion of Xpert and Smear results.
14% of the Xpert positive samples were smear negative and only
diagnosed by Xpert testing. Another 26% of samples were indeterminate and Xpert helped confirm the diagnosis. No sputum yielded a
positive smear and negative Xpert.
Xpert increased detection by 16% if scanty smears are considered
positive, or 65% if scanty smears are considered negative.
Cost per smear negative case detected is shown in Table 2 (note the
two calculations based on how scanty smears classified).
High cost of Xpert MTB/RIF testing per excess tuberculosis
case diagnosed at Partners in Hope Medical Center,
a public-private HIV care clinic in Lilongwe, Malawi.
Comparison with fluorescence microscopy in a wellequipped and experienced real world AFB laboratory
D. Fitzgerald1,2, P. Jansen1, C. Chipungu1, V. Dindi1, J. Fielder1 and
C. Pfaff1,2
1
Partners in Hope, Lilongwe, Malawi. 2University of California, Los
Angeles, Program in Global Health, Los Angeles, United States
Presenting author email: colinpfaff@yahoo.co.uk
AFB smear
Positive
Total cost
to detect
Total
Smear
NNT to
one
smear negative detect
smear
negative
with
one
Cost per negative
sputum positive
smear
test
case with
samples
Xpert
negative cartridge
Xpert
‘‘Scanty’’
smears
considered
positive
‘‘Scanty’’
smears
considered
negative
367
8
46
$20
$920
382
23
17
$20
$340
Cost to detect one smear negative case.
Conclusion: Xpert MTB/RIF increased TB detection by 16%-65%
compared to fluorescence microscopy in a well-equipped laboratory.
The Xpert may perform differently in a less sophisticated laboratory.
However, cost per case detected was high and not affordable in
Malawi.
THAB0105
Implementing Xpert† MTB/RIF in rural Zimbabwe: impact
on diagnosis of smear-negative TB and time-to-initiation of
TB treatment in smear-negative patients co-infected with
HIV
H. Bygrave1, S. Simons2, D. Munyaradzi2, B. Nyagadza2, C. Metcalf1,
K. Ncube3 and S. Van Den Broucke2
1
Medecins Sans Frontieres, South African Medical Unit, Cape Town,
South Africa. 2Medecins Sans Frontieres, Harare, Zimbabwe.
3
Ministry of Health and Child Welfare Zimbabwe, Buhera, Zimbabwe
Presenting author email: helen.bygrave@joburg.msf.org
44
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Background: Xpert† MTB/RIF is a new molecular diagnostic tool,
developed to increase detection and shorten time to diagnosis of
sputum-smear-negative (SSN) tuberculosis (TB). In April 2011,
Médecins Sans Frontières (MSF) in collaboration with the
Zimbabwean Ministry of Health and Child welfare implemented
two Xpert† MTB/RIF systems in a rural district in Zimbabwe serving
two hospitals and 26 decentralised primary care clinics.
Methods: From May to October 2011, parallel testing with both
smear microscopy and Xpert† MTB/RIF was performed on specimens from all TB suspects. We used information abstracted from
clinical and laboratory records to compare the number of laboratoryconfirmed TB cases, number of TB notifications, and the time to
diagnosis among HIV/TB co-infected patients with sputum-smearnegative TB during 6 months before and after Xpert† MTB/RIF
implementation.
Results: A total of 1672 sputum specimens were processed, of which
184 (11.0%) were smear-positive. Mycobacterium tuberculosis was
detected by Xpert† MTB/RIF in 116 (7.8%) of the 1488 remaining
smear-negative specimens. Comparing the period after implementing Xpert† with the period before, the proportion of TB notifications
that were smear positive (33% versus 27%), smear-negative (48%
versus 49%), sputum not tested (11% versus 12%), and extrapulmonary (8% versus 12%) was unchanged. The median time to TB
treatment initiation among HIV/TB co-infected patients with sputumsmear-negative TB, decreased at decentralised sites (from 18.5 days
to 7 days), but remained constant at the hospital level (5.5 days
before and 6 days after).
Conclusion: Xpert† MTB/RIF increased the number of laboratoryconfirmed TB cases in rural Zimbabwe, enabling further task shifting
of TB management. In settings where access to chest X-Ray and
trained doctors is lacking the impact on TB notifications may be
greater. Time-to-initiation of TB treatment at the decentralized clinics
was reduced, which has the potential to reduce morbidity in
individuals and reduce the risk of TB transmission to others.
THAB0104
The value of universal TB screening with GeneXpert MTB/
RIF in pre-ART patients in Harare
L. Mupfumi1,2, P. Mason1, S. Zinyowera3,4 and R. Mutetwa1
1
Biomedical Research & Training Institute, Harare, Zimbabwe.
2
University of Zimbabwe College of Health Sciences, Medical
Laboratory Sciences, Harare, Zimbabwe. 3National Microbiology
Reference Laboratory, Harare, Zimbabwe. 4University of Zimbabwe
College of Health Sciences, Medical Microbiology, Harare, Zimbabwe
Presenting author email: lmupfumi@gmail.com
Background: Recently, WHO recommended that GeneXpert MTB/RIF
be used as first line diagnostic to test for TB in HIV positive
individuals. Most patients initiating ART lack the classical symptoms
for TB resulting in missed diagnosis. The role of symptom screen in
predicting a positive GeneXpert result among pre-ART patients was
studied.
Methods: This was a nested cohort study within a GeneXpert impact
evaluation trial in pre-ART patients. TB symptomatic and asymptomatic adults ( 18 yrs) at an ART initiation clinic in Harare were
recruited between October 2011 and February 2012. For each
patient, two spot sputum samples were collected and induction with
6% hypertonic NaCl performed in those who could not expectorate.
Sputum samples were tested with GeneXpert (Cepheid) Test.
Participants were followed-up for 3months.
Results: 150 participants were recruited and 126 produced specimens and were tested for TB using GeneXpert. Median CD4
Track B Clinical Science
count was 165cells/ul (IQR 79256). Fifty-four percent of the
participants had a cough (68/126). Induction was carried out in 19
participants and of these, 47% (9/19) were coughers and 53% (10/
19) non-coughers. TB was diagnosed in 10% of participants (13/126;
95% CI 416); with an additional 2 cases diagnosed on second
GeneXpert test. Significant predictors of disease were cough of any
duration (p 0.019), night sweats (p0.03) and weight loss
(p 0.04). Of those induced, 16% (3/19) had a positive GeneXpert
result. Notably, induced samples accounted for 23% (3/13) of
the TB cases detected. Three percent (2/58) of the non-coughers
were GeneXpert positive. Seven participants (5%) with negative
GeneXpert results were started on TB treatment based on clinical
suspicion.
Conclusion: TB testing using GeneXpert in pre-ART patients, with
sputum induction, should be carried out routinely regardless of
patient TB symptom status. A two step screening test and Xpert
testing algorithm is needed for scale-up of universal TB testing in
pre-ART patients.
THLBB02
Safety, tolerability and early bactericidal activity in sputum
of PNU-100480 (sutezolid) in patients with pulmonary
tuberculosis
R.S. Wallis1, A.H. Diacon2, R. Dawson3, A. Venter2, S.O. Friedrich2,
D. Paige1, T. Zhu1, A. Silvia1, J. Gobey1, C. Ellery1, Y. Zhang1 and
E. Kadyszewski1
1
Pfizer, Groton, United States. 2Stellenbosch University, Stellenbosch,
South Africa. 3U Cape Town, Cape Town, South Africa
Presenting author email: robert.wallis@pfizer.com
Background: PNU-100480 is a linezolid analog with superior
bactericidal activity against Mycobacterium tuberculosis in the
hollow fiber, whole blood and mouse models that is time-dependent
and unaffected by resistance mutations for standard TB drugs. PNU100480 neither induces nor inhibits CYP3A4. This study is its first in
TB patients.
Methods: Sputum AFB smear positive South African patients
(incl. HIV not requiring ART) were randomly assigned to PNU100480 600 mg BID (N 25) or 1200 mg QD (N 25), or standard
4-drug therapy (HREZ, N9) for the first 14 days of treatment.
Sputum mycobacterial burden was monitored both as log CFU/ml
and time to detection (TTP) in automated liquid culture system
(MGIT).
Results: 20% of subjects were women; 7% were HIV. All subjects
completed assigned treatments. There were no treatment-related
serious adverse events nor any permanent discontinuations or dose
reductions due to laboratory abnormalities. There was no effect on
the QT interval. At baseline, the mean log CFU/ml and TTP were 6.95
and 116 hrs, respectively. Changes in mycobacterial burden during
treatment are shown below. Lines indicate estimates by mixed-effect
model repeated measures (MMRM) analysis; shading indicates
90% CI. MMRM analysis revealed that the 90% CI after the full
treatment period excluded zero for all 3 treatments and for both
monitoring methods. Seven PNU-treated patients (14%) had
transient, asymptomatic ALT elevations on day 14 to 23x ULN that
subsequently returned promptly to normal; none met Hy’s law
criteria.
Conclusion: Treatment with PNU-100480 600 mg BID or 1200 mg
QD reduced the mycobacterial burden in sputum during 14 days
of treatment. Both treatments were safe and reasonably well
tolerated. Further studies of PNU-100480 in tuberculosis are
warranted.
45
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
Figure 1.
EBA.
THPDB0106
Adverse events in an integrated, home-based treatment
program for MDR-TB and HIV in Tugela Ferry, South Africa
J.C.M. Brust1, N.S. Shah1, T.L. van der Merwe2,3, S. Bamber3,
A. Mngadi4, Y. Ning5, M. Heo5, A.P. Moll2,3, M. Loveday6,7,
U.G. Lalloo7, G.H. Friedland8 and N.R. Gandhi1
1
Montefiore Medical Center & Albert Einstein College of Medicine,
Medicine, Bronx, United States. 2Church of Scotland Hospital,
Tugela Ferry, South Africa. 3Philanjalo, Tugela Ferry, South Africa.
4
Greytown Hospital, Greytown, South Africa. 5Montefiore Medical
Center & Albert Einstein College of Medicine, Bronx, United States.
6
South African Medical Research Council, Health Systems Research
Unit, Cape Town, South Africa. 7Nelson R Mandela School of
Medicine, University of KwaZulu Natal, Durban, South Africa.
8
Yale University School of Medicine, New Haven, South Africa
Presenting author email: jcmbrust@gmail.com
Background: More than 80% of patients with multidrug-resistant
tuberculosis (MDR-TB) in Tugela Ferry, South Africa are co-infected
AEs by 6-month time blocks.
with HIV. Concomitant treatment for both diseases is recommended,
but concern about severe and additive toxicities of MDR-TB therapy
and ART has slowed acceptance of community-based treatment.
Methods: Confirmed MDR-TB patients were treated at home by an
injection team and returned to the clinic monthly where they were
screened for common adverse events (AEs). Severity was graded
using the DAIDS toxicity table. Safety labs were drawn monthly and
TSH was drawn every 3 months. We reviewed clinical and laboratory
AEs for all patients between November 2008 and April 2011.
We examined the incidence of each AE in 6-month time blocks
and the within-patient trend of each AE over time. We compared
those who received concomitant MDR-TB/ART treatment to those
who received MDR-TB treatment alone.
Results: Of 91 MDR-TB patients, 55% were female; median age was
34 (IQR 2941); and 84% were HIV co-infected. 74 patients (97% of
HIV) were receiving ART and median baseline CD4 cell count was
207 cells/mm3 (IQR: 89411). Ninety-nine percent of patients
reported at least one AE during treatment, but most were mild
and did not require therapy modification. The most common AEs
were peripheral neuropathy (73%), injection site pain (66%), and
arthralgia (43%). The most common severe AEs (grade3) were
psychosis (10%) and hypothyroidism (29%). Patients receiving
concurrent ART did not experience AEs more frequently than those
on MDR-TB therapy alone. Patients were significantly less likely to
report most AEs later in their treatment course (Figure 1).
Conclusion: Home-based treatment of MDR-TB and HIV is associated
with high rates of mild AEs which are not increased by concurrent
ART and can be managed symptomatically without changing MDR-TB
therapy or ART. Treatment can be safely administered in a homebased care setting.
B15 - Hepatitis B and D, including
treatment
MOAB0101
Prevalence of hepatitis B co-infection and response to
antiretroviral therapy among HIV-positive patients in urban
Tanzania
C. Hawkins1,2, B. Christian2, J. Ye3, T. Nagu4, E. Aris2,4, G. Chalamilla2,3,
D. Spiegelman3, F. Mugusi4, S. Mehta5 and W. Fawzi2,3
1
Northwestern University, Infectious Diseases, Chicago, United
States. 2Management and Development for Health, Dar es Salaam,
46
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
United Republic of Tanzania. 3Harvard School of Public Health,
Boston, United States. 4Muhimbili University of Health and Allied
Sciences, Dar es Salaam, United Republic of Tanzania. 5Cornell
University, New York, United States
Background: The effect of chronic hepatitis B (HBV) on HIV outcomes
is relatively unknown in sub-Saharan Africa (SSA) where a high
burden of HIV-HBV co-infection exists.
Methods: Clinical and immunologic outcomes in response to ART
were compared longitudinally between HIV mono- (HIV) and HIVHBV co-infected (HIV&HBV) adults enrolled between November
2004-December 2010 at 18 Management and Development for
Health (MDH)-PEPFAR supported HIV clinics in Tanzania. Inclusion
criteria were: tested ]1 for HbsAg (DIMA), age ]15, no prior ART.
Results: The prevalence of HBV was 837/13,107 (6.4%).Compared to
HIV patients, HIV&HBV patients were more likely to be male,
older, have lower median CD4 cell counts, and higher ALT’s (p
valuesB0.05) prior to ART initiation. Mean follow up time on ART
was 9.8 (SD 7.8) and 10.1 (SD 7.5) months in HIV&HBV and HIV
patients respectively. In multivariate analyses, there were no
significant differences in overall mortality [HR 1.17 (95% CI
0.87,1.33); p 0.52] between HIV&HBV and HIVpatients.
CD4 count response also did not significantly differ between the
2 patient groups (p 0.11). HIV&HBV patients had a significantly
higher risk of ALT120IU/L [38/813 (4.7%) vs. 303/12,136 (2.5%); HR
1.76 (1.25, 2.49), pB0.01] and ALT200IU/l [20/831 (2.4%) vs. 102/
12,236 (0.8%); HR 2.74, (1.66, 4.05), p B0.01]. HBV vs. negative
status was associated with a significantly lower mortality among
patients on tenofovir (TDF) [HR 0.40 (95% CI -0.190.85; pB0.02)];
but higher mortality among patients on ART not containing TDF [HR
1.70 (95% CI -1.342.15; pB0.01)]; [interaction p-value (B0.01)].
Conclusion: Co-infection with HBV did not significantly impact
mortality or immunologic outcomes in HIV-infected patients on
ART in this SSA setting. However, routine monitoring of ALT levels
after ART initiation in co-infected individuals is recommended. TDF
should be included in initial ART for HIV&HBV co-infected individuals,
given the significant mortality benefit observed.
Track B Clinical Science
Background: Few studies have examined the natural history of
chronic hepatitis C virus (HCV) infection among HIV-infected persons
in the era of combination antiretroviral therapy (cART). Our
objectives were to: 1) compare the incidence of hepatic decompensation between cART-treated HIV/HCV-coinfected and HCVmonoinfected patients, and 2) evaluate determinants of decompensation among coinfected patients on cART.
Methods: We performed a cohort study among 4,286 cART-treated
HIV/HCV-coinfected and 6,639 HCV-monoinfected patients in the
Veterans Aging Cohort Study Virtual Cohort (19972010). All
patients had HCV viremia and were HCV treatment-naı̈ve. Coinfected patients received cART for at least one year and had an
HIV RNA result 500 copies/mL within 180 days prior to starting
cART (to identify new cART initiators). Hepatic decompensation
events (defined by diagnoses of ascites, spontaneous bacterial
peritonitis, variceal hemorrhage, or hepatocellular carcinoma) and
death were evaluated. Cox regression was used to determine the
adjusted hazard ratio (aHR) of hepatic decompensation associated
with cART-treated coinfection and evaluated baseline risk factors
for decompensation (alcohol abuse, non-black race, diabetes
mellitus, FIB-4 3.25, hemoglobin B10 g/dL, and pre-cART CD4
count) in coinfected patients on cART.
Results: Compared to HCV-monoinfected patients, cART-treated HIV/
HCV-coinfected had a higher cumulative incidence and risk of hepatic
decompensation (303/4,286 [7.1%] versus 370/6,639 [5.7%];
aHR 1.76 [1.502.06]) and hepatocellular carcinoma (50/4,286
[1.2%] versus 60/6,639 [0.9%]; aHR1.69 [95% CI 1.142.49]).
After decompensation, mortality was higher in coinfected patients
(228/303 [75.2%] vs. 210/370 [56.8%]; pB 0.001). Non-black race
(aHR 1.96 [1.532.49]), baseline FIB-4 3.25 (aHR 7.18
[5.12 10.07]), and baseline hemoglobin B10 g/dL (aHR 2.86
[1.62 5.07]) were associated with decompensation among coinfected patients.
Conclusion: Despite cART, HIV/HCV-coinfected patients had a higher
risk of hepatic decompensation and death compared to HCVmonoinfected individuals. Risk of decompensation was higher for
coinfected patients with advanced liver fibrosis, severe anemia, and
non-black race.
B16 - Hepatitis C, including treatment
WEAB0102
Increased risk of hepatic decompensation and
hepatocellular carcinoma in HIV/HCV-co-infected patients
compared to HCV-mono-infected patients despite
combination antiretroviral therapy
V. Lo Re1,2, J. Tate3,4, M. Kallan1, J. Lim3,4, M. Goetz5, M. Klein6,
D. Rimland7, M. Rodriguez-Barradas8, A. Butt9, C. Gibert10,
S. Brown11, J. Kostman1, B. Strom1, R. Reddy1, A. Justice3,4 and
R. Localio1
1
Perelman School of Medicine, University of Pennsylvania,
Philadelphia, United States. 2Philadelphia VA Medical Center,
Philadelphia, United States. 3VA Connecticut Healthcare System,
West Haven, United States. 4Yale University School of Medicine
New Haven, United States. 5VA Greater Los Angeles Healthcare
System, Los Angeles, United States. 6McGill University Health
Centre, Montreal, Canada. 7Atlanta VA Medical Center
Atlanta, United States. 8Michael E. DeBakey VA Medical Center,
Houston, United States. 9VA Pittsburgh Healthcare System,
Pittsburgh, United States. 10Washington DC VA Medical Center,
Washington, United States. 11James J. Peters VA Medical Center, New
York, United States
Presenting author email: vincentl@mail.med.upenn.edu
WEAB0103
The addition of nitazoxanide to peginterferon alfa-2a and
ribavirin does not significantly improve sustained virologic
response in HCV treatment-naı̈ve genotype 1 HIV-1/HCV
co-infected subjects: results of ACTG 5269
V. Amorosa1,2, T. Umbleja3, V. Johnson4,5, M. Kang3, A. Luetkemeyer6,
M. Bardin7, D. Haas8, R. Chung9, S. Yesmin10, K. Coughlin11,
A. Martinez12, M.B. Adams13, B. Alston-Smith12, P. Tebas2 and
M. Peters6
1
Philadelphia Veterans Affairs Medical Center, Medicine,
Philadelphia, United States. 2University of Pennsylvania,
Medicine, Philadelphia, United States. 3Harvard School of Public
Health, Boston, United States. 4Birmingham VA Medical Center,
Birmingham, United States. 5University of Alabama Birmingham,
Medicine, Birmingham, United States. 6University of San Francisco,
San Francisco, United States. 7Romark, Tampa, United States.
8
Vanderbilt University, Nashvile, United States. 9Harvard Medical
School, Boston, United States. 10ACTG Operations Center
Bethesda, United States. 11Frontiers Science & Technology
Research Foundation, Amherst, United States. 12DAIDS, NIAID, NIH,
Bethesda, United States. 13University of Rochester, Rochester, United
States
Presenting author email: marion.peters@ucsf.edu
47
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
Background: HIV-1/HCV coinfected patients respond poorly to
pegylated interferon(PEG-IFN) and weight-based ribavirin(WBR),
with sustained virologic response(SVR) of 27% in genotype 1 HCV
treatment-naı̈ve subjects (ACTG 5178 results). Nitazoxanide(NTZ)
plus PEG-IFN and WBR has demonstrated improved efficacy in HCV
monoinfected subjects. We hypothesized that addition of NTZ to
PEG-IFN/WBR would improve HCV virologic responses in HIV-1/HCV
co-infected persons.
Methods: HIV-1/HCV genotype 1 co-infected subjects naı̈ve to HCV
treatment received 4-week lead-in of NTZ(1000 mg/day) followed by
48 weeks of NTZ, PEG-IFN alfa-2a(180 mg/week) and WBR(1000
1200 mg/day). SVR was defined as undetectable serum HCV RNA
( B43 IU/mL 24 weeks following end of treatment; Roche TaqMan
HCV, v1.0). SVR proportion was compared with historical control
proportion from ACTG 5178, using one-sided Fisher’s exact test. Early
virologic response(EVR, ]2-log10 IU/mL decrease from entry), complete EVR(cEVR, undetectable serum HCV RNA) after 12 weeks triple
therapy, and rapid virologic response(RVR, undetectable after 4
weeks triple therapy) were previously presented. IL28B rs12979860
genotyping was done by ABI TaqMan.
Results: 67 subjects enrolled: 78% male, 48% black, 31% white, 18%
Hispanic, median age 50 years, median entry CD4 T-cell count 452
cells/mm3 and HCV RNA 6.38 log10 IU/mL. 73% had undetectable
HIV-1 RNA. SVR was achieved in 22 subjects(32.8%, 90% CI 23.4
43.5%) compared to 27.3% in A5178 (p 0.24). SVR proportion was
86% among those who achieved RVR(6 of 7),50% among those who
achieved EVR(22 of 44), 77% among those who achieved cEVR (20 of
26) and 6% among those who did not achieve cEVR (2 of 35). In
contrast to A5178, SVR did not differ across IL28B genotypes (N 62,
See table). Adverse events attributable to NTZ included diarrhea and
nausea.
N
C/C
C/T
T/T
SVR proportion (95% CI)
A5178
A5269
A5178
A5269
38
51
23
15
37
10
42% (2659%)
33% (2148%)
4% (022%)
33% (1262%)
30% (1647%)
30% (765%)
SVR proportion by IL28B genotype.
Conclusion: In genotype 1 HCV treatment-naı̈ve HIV-1/HCV coinfected subjects in this pilot study, the addition of NTZ to PEGIFN/WBR did not significantly improve SVR compared to historical
controls with PEG-IFN/WBR.
B18 - Prophylaxis of HIV associated
infections; vaccines e.g., pneumococcal,
hepatitis and HPV, co-trimoxazole
prophylaxis and Isoniazid Preventive
Therapy (IPT)
WEAB0202
Immunogenicity of the HPV-6, -11, -16, -18 vaccine in
HIV-positive young women
J. Kahn1, J. Xu2, B. Kapogiannis3, B. Rudy4, N. Liu2, R. Gonin2,
C. Wilson5, C. Worrell3 and K. Squires6
1
Cincinnati Children’s Hospital Medical Center, Pediatrics, Cincinnati,
United States. 2Westat Inc., Rockville, United States. 3NICHD/PAMAB,
Rockville, United States. 4New York University, New York
United States. 5University of Alabama at Birmingham - School of
Public Health, Birmingham, United States. 6Jefferson Medical
College, Philadelphia, United States
Presenting author email: jessica.kahn@cchmc.org
Background: The objective of this study was to examine the
immunogenicity of the HPV-6, -11, -16, -18 vaccine in HIV-infected
young women.
Methods: This phase II, open-label, multi-center trial was conducted
through the Adolescent Trials Network for HIV/AIDS Interventions.
Participants were 16-23 year-old women behaviorally infected with
HIV. Two groups were enrolled: Group A (ART naÿve or had not
received HAART for at least six months prior to study entry) and
Group B (had received HAART for at least 6 months, with two HIV-1
RNA plasma viral loads B400 copies/mL). Participants received the
HPV-6, -11, -16, -18 vaccine at baseline and study weeks 8 and 24;
immunogenicity testing was performed before the first dose and 4
weeks after the third dose. Immunogenicity was measured by 1)
mean geometric mean titers (GMTs) and 2) seroconversion rates for
HPV-6, -11, -16, and -18, among those seronegative and HPV DNA
negative for each type at baseline. One sample t-tests and one-arm
comparisons were used to compare mean GMTs and seroconversion
rates, respectively, of participants vs. historical controls (N=276) who
were HIV-negative (Villa et al., 2006).
Results: The mean age of the 99 subjects was 21.4 years, and 80%
were Non-Hispanic Black. At baseline, 85% had a CD4+ count ]350
cells/mm3, 40% had a HIV viral load B400 copies/mL, 56% were
seronegative and HPV DNA negative for HPV-16, and 74% were
seronegative and HPV DNA negative for HPV-18. Mean GMTs and
Mean GMTs
Group A
Group B
All
Controls/
(N 69)
(N30)
(N99)
P value (2)
Group A (N 69)
Group B (N 30)
All (N 99)
P value (2)
Controls/
mean
mean
mean
mean/P value
%
%
%
%/P value
HPV-6
547
1139
739
582/0.28
96.3
100
97.5
HPV-11
655
1454
896
697/0.17
95.5
100
96.8
100/0.07
HPV-16
2176
5037
2961
3892/0.05
94.6
100
96.1
100/0.08
HPV-18
445
963
577
801/0.03
90.0
100
92.5
100/0.01
100/0.16
(1) Proportion with GMTs to HPV-6, -11, -16, and -18 of at least 20, 16, 20, and 24 mMU/mL, respectively.
(2) P value assesses differences in mean GMTs or seroconversion rates 4 weeks after the third vaccine dose for all subjects vs. controls. When
GMTs and seroconversion rates for Group A and Group B participants were compared to those of controls, the only significant differences were
in Group A subjects vs. controls for HPV-18; no differences were found in Group B subjects vs. controls.
48
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
seroconversion rates for subjects and controls are shown in the
Table.
Conclusion: Among HIV-infected young women who were HPV DNA
and HPV seronegative at the time of vaccination, HPV type-specific
immune responses to vaccination were generally robust. Subjects
not on HAART vs. controls had significantly lower mean GMTs and
seroconversion rates for HPV-18 only; no differences were found
between subjects on HAART and controls.
WEAB0203
Results: We report preliminary safety and week 28 seroconversion
results from A and B. At baseline, median age was 37 years
(range 1945), 13% were white, 57% black, and 29% Hispanic.
Median nadir CD4 was 262 cells/mm3, 41% had undetectable HIV-1
viral load, 13% from non-US sites. No safety issues were identified;
none of the grade ]3 AEs was thought to be vaccine-related.
Proportion of Women who Seroconverted 4 weeks After the
Vaccination Series.
Conclusion: Quadrivalent HPV vaccine targeted at types 6, 11, 16,
and 18 is safe and highly immunogenic in HIV-infected women 1945
years old with CD4 200.
Safety and immunogenicity of the quadrivalent human
papillomavirus vaccine in HIV-positive women
E.M. Kojic1, M. Cespedes2, T. Umbleja3, M. Kang3, J. Aberg2, R. Allen4,
B. Grinsztein5, C. Firnhaber6, J. Webster-Cyriaque7, J.M. Palefsky8,
C. Godfrey9, A.J. Saah10 and S. Cu-Uvin1
1
Brown University-The Miriam Hospital, Infectious Diseases,
Providence, United States. 2New York School of Medicine, New York,
United States. 3Harvard School of Public Health, Boston, United
States. 4ACTG Operations Center, Silver Spring, United States.
5
Chagas Fiocruz, Rio de Janeiro, Brazil. 6University of Witwatersrand,
Johannesburg, South Africa. 7University of North Carolina, Chapel
Hill, United States. 8University of California at San Francisco, San
Francisco, United States. 9NIAID NIH, Bethesda, United States.
10
Merck Research Labs, North Wales, United States
Presenting author email: ekojic@lifespan.org
Background: HIV-infected women are disproportionately affected by
human papillomavirus (HPV)-related anogenital disease. A5240 is a
clinical trial of 319 HIV-infected women at US, Brazil and South Africa
sites to determine immunogenicity and safety of the quadrivalent
HPV vaccine.
Methods: Safety and serostatus of HPV types 6, 11, 16, and 18 were
examined in 222 women. The vaccine was administered at 0, 8, 24
weeks in 3 strata based on screening CD4: 350 (A), 201-350 (B),
5200 cells/mm3 (C). HPV serotyping was performed using competitive Luminex Immuno-Assay (HPV-4 cLIA). HPV type-specific
seroconversion analysis was on participants seronegative for the
given type at baseline. Seroconversion was defined by: ]20, ]16,
]20, ]24 mMU/mL for types 6, 11, 16, 18 respectively. Two-sided
95% CIs are provided.
HPV Type
Baseline
seronegatives
Stratum A
CD4350
>Seroconversion
proportion
(95% CI)
Geometric
Mean
Titers (95% CI)
Stratum
B 200 BCD4
B350
Seroconversion
proportion
(95% CI)
Geometric
Mean
Titers (95% CI)
Seroconversion.
6
11
16
18
N 50
N 79
N62
N73
96%
(8699%)
97%
98%
(91100%) (91100%)
425
(289627)
454
(337611)
N 44
N 55
1088
160
(7771524) (114225)
N52
100%
98%
98%
(92100%) (90100%) (90100%)
324
(217483)
407
(277600)
90%
(8196%)
N66
85%
(7493%)
1090
171
(7221646) (114257)
B18 - Prophylaxis of HIV associated
infections; vaccines e.g. pneumococcal,
hepatitis and HPV, co-trimoxazole
prophylaxis and Isoniazid Preventive
Therapy (IPT)
THLBB03
Randomized controlled trial of isoniazid preventive therapy
in HIV-infected persons on antiretroviral therapy
M.X. Rangaka1,2,3, A. Boulle1, R.J. Wilkinson2,4, G. van Cutsem1,5,
E. Goemaere5, R. Goliath2, R. Titus2, S. Mathee6 and G. Maartens7
1
University of Cape Town, School of Public Health, Centre for
Infectious Disease Epidemiology and Research, Cape Town,
South Africa. 2University of Cape Town, Institute of Infectious
Diseases and Molecular Medicine, Clinical Infectious Diseases
Research Initiative, Cape Town, South Africa. 3London School of
Hygiene and Tropical Medicine, (LSHTM), London, United Kingdom.
4
Imperial College London, Division of Medicine, London,
United Kingdom. 5Medecins Sans Frontieres South Africa, Khayelitsha
ART Programme, Khayelitsha, Cape Town, South Africa. 6Provincial
Government of the Western Cape, Cape Town, South Africa.
7
University of Cape Town, Department of Medicine, Pharmacology
Unit, Cape Town, South Africa
Presenting author email: mxrangaka@yahoo.co.uk
Background: Antiretroviral therapy (ART) reduces the risk of tuberculosis, but the incidence still exceeds that in HIV-uninfected
people. Retrospective cohort studies suggest an additive benefit of
isoniazid preventive therapy (IPT) in patients on ART, but there
are no controlled data on the efficacy and safety of IPT for patients on
ART.
Methods: Using a pragmatic randomized double-blind placebocontrolled study design, we evaluated the efficacy of IPT among
HIV-infected participants established on ART or newly starting
ART in Khayelitsha, South Africa. Participants were randomized to
daily isoniazid or matching placebo for twelve months, and followed
for up to four years. Tuberculosis was excluded at screening by
sputum culture. Development of incident tuberculosis was the
primary endpoint. Secondary endpoints included toxicities and
deaths.
Results: 1,329 participants contributed 3227 person-years (PY) of
follow-up in the modified intention to treat analysis; 662 on placebo
and 667 on IPT, with comparable CD4count and proportion
starting ART. Overall there were 95 incident tuberculosis cases: 3.6
(95% CI 2.84.7) versus 2.3 (95% CI 1.63.1) per 100 PY in the
placebo and IPT arms respectively (HR 0.63, 95% CI 0.410.94,
p0.026). Study drug was discontinued due to pre-specified toxicity
in 2.5% in the placebo arm and 4.1% in the IPT arm (logrank
49
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
p0.13). The number of deaths was similar between arms (3.0% and
2.1 respectively, logrank p0.29).
Conclusion: Under field conditions, twelve months of IPT reduced
the incidence of TB without causing excess harm in HIV-infected
individuals established on ART or newly starting ART. It is feasible to
implement IPT in busy ART clinics in settings with high HIV/TB comorbidity.
B19 - HIV-associated neurocognitive
disorders (HAND) and other neurologic
disorders
MOAB0204
Cognitive, neurological and adaptive behaviour functioning
among children with perinatally-acquired HIV infection in
India
A. Shet1, S. Holla1, V. Raman2, C. Dinakar1 and M. Ashok2
1
St Johns National Academy of Health Sciences, Paediatrics,
Bangalore, India. 2St Johns National Academy of Health Sciences,
Psychiatry, Bangalore, India
Presenting author email: anitashet@gmail.com
Background: With improved survival of HIV-infected children,
neurocognition is an important area to address. We examined the
effects of HIV infection on cognitive, neurological, and behavioral
functioning on perinatally-infected children.
Methods: HIV-infected children (415yrs) were recruited from a
tertiary-care center in India, along with age-gender-and-incomematched HIV-negative children. Assessment tools included (i) soft
neurological signs: Physical and Neurological Examination for Soft
Signs (PANESS); (ii) neurocognition: culturally-adapted Wechsler
Preschool and Primary Scales of Intelligence (WPPSI), Wechsler
Intelligence Scale for Children (WISC-III); (iii) adaptive behaviour:
Vineland Adaptive Behaviour Scales (VABS).
Results: We studied 167 children, (82 HIV-infected, 85 HIV-uninfected) with 56% males and mean age 8.6 yrs. Total IQ scores were
lower among HIV-infected children compared to HIV-uninfected
children (74.9 12.9 versus 87.915.4, p B0.001). Both domains of
verbal IQ and performance IQ were uniformly affected. Severely
immunosuppressed children (CD4 B20%) had lower total IQ scores
(70.712.3) compared to those with CD420%, (IQ 77.112.8,
p0.03). Viral load and ART status has no effect on IQ scores.
Multivariate regression revealed that HIV status, weight-forage Z-score and hemoglobin were independent factors that affected
IQ scores (adjusted r2 0.25, p0.006). The presence of HIV
infection independently decreased IQ scores by 9.22 units. PANESS
scores were higher among HIV-infected children compared to
uninfected children (HIV-positive: 7.5, [3, 13.3]; HIV-negative: 4,
[1.5, 9.5], p 0.02) suggesting higher degree of subtle neurological
abnormalities in this group. Adaptive behaviour scores were
similar for both HIV-infected and uninfected children irrespective
of age and sex.
Conclusion: HIV-infected children had lower IQ scores and higher
prevalence of soft neurological signs compared to HIV-uninfected
children, indicating that subtle neurocognitive impairment is an
important feature of perinatally-acquired HIV infection, particularly
those with poor nutritional status. We recommend routine neurocognitive assessment and suggest that early intervention with
initiation of ART before the onset of severe immunosuppression
may improve outcomes in these children.
Track B Clinical Science
THAB0203
Type 2 diabetes is associated with lower cognitive
performances in a cohort of HIV-positive patients. ANRS
CO3 Aquitaine Cohort, Bordeaux, France, 20072009
C. Dufouil1, L. Richert1, M. Bruyand1, H. Amieva1, F.-A. Dauchy2,
J.-F. Dartigues1, D. Neau2, F. Dabis3, P. Morlat2, F. Bonnet2 and
G. Chene1, ANRS CO3 Aquitaine Study Group
1
INSERM Center 897, CIC-EC7, Bordeaux, France. 2Bordeaux Hospital,
Bordeaux, France. 3INSERM Center 897, Bordeaux, France
Presenting author email: carole.dufouil@isped.u-bordeaux2.fr
Background: HIV infected patients receiving combination antiretroviral therapy are at higher risk of cardiovascular morbidity and have
accelerated aging notably of cognitive functions. The link between
cardiovascular risk factors and cognition has rarely been investigated
in HIV-infected cohorts. In a large hospital-based cohort, we explored
whether cardiovascular risk factors are associated with cognitive
performances.
Methods: The ANRS-CO3 Aquitaine Cohort recruits patients through
a hospital-based information system on HIV-1 infection in the
Bordeaux University Hospital in the Aquitaine region, South Western
France. Between 2007 and 2009, 403 patients participated in a substudy and had a thorough assessment of several cognitive domains.
Cognitive performances were analyzed using both the raw test
scores and the presence of neurocognitive impairment (NCI), based
on the most recent definition of HIV-associated neurocognitive
disorders.
Selected cardiovascular risk factors were type 2 diabetes, hypertension, hypercholesterolemia, smoking status and BMI.
Covariance analyses were computed to investigate the association between cardiovascular risk factors and raw cognitive test
scores, adjusting for potential confounders. Logistic regression
with the same covariates was used to analyse NCI as dependent
variable.
Results: Mean age was 47.3 years and 79% were male. The
prevalence of cardiovascular risk factors ranged from 9.7% for
diabetes to 49.6% for current smoking, and 37.7% of participants
had NCI.
Lower performances in all cognitive tests were related to older age
and lower education. Among cardiovascular risk factors, diabetes
was significantly associated with lower performances in all cognitive
tests after adjusting for potential confounders. By contrast, no such
consistent associations were noted for any other cardiovascular risk
factors. Diabetes prevalence did not significantly differ by NCI status
(p 0.44).
Conclusion: In this hospital-based cohort, diabetes, but not the other
cardiovascular risk factors, is associated with lower performances in
all assessed cognitive domains. The mechanisms underlying our
findings remain to be clarified but could involve inflammation and
microcirculation.
THAB0204
Stroke in human immunodeficiency virus (HIV) infected
patients
M. Nigo1, A. Walker2, D. Lucido3, A. Shah2, M. Skliut2 and D. Mildvan4
1
Beth Israel Medical Center, and Albert Einstein College of Medicine,
Internal Medicine, New York, United States. 2Beth Israel Medical
Center, and Albert Einstein College of Medicine, Neurology
New York, United States. 3Beth Israel Medical Center, and Albert
Einstein College of Medicine, New York, United States. 4Beth Israel
Medical Center, and Albert Einstein College of Medicine, Infectious
Diseases, New York, United States
Presenting author email: masa25103@gmail.com
50
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
Background: Current literature indicates that infection with HIV
contributes to an increased risk of acute stroke. The goal of this study
is to compare clinical and epidemiological characteristics of stroke
patients with and without HIV infection.
Methods: We performed a retrospective chart review of stroke
patients who were admitted to the stroke unit between January of
2005 and June of 2011. We identified 43 patients with known HIV
infection at the time of admission for acute stroke. 101 controls were
randomly selected from non-HIV patients who had acute stroke
within the same time period. Clinical and epidemiological characteristics of two groups were compared.
Results: Of 1679 admissions with acute stroke, 43 (2.6%) were in
HIV-infected patients (32 males, 11 females) and 101 in non-HIV
infected patients (45 males, 56 females). Mean age was 57.8 years
and 72.6 years, respectively. All 144 patients had acute ischemic
stroke confirmed by imaging. Significant difference was identified in
age, race, blood pressure on admission, National Institute of Health
Stroke Scale (NIHSS) on admission, and HDL level (Table 1). The
presence of co-morbidities (HTN, DM, hyperlipidemia), body mass
index (BMI), homocysteine level, LDL, and coagulation profiles were
Table 1.
not statistically different between two groups. In the HIV group, 30
patients (83%) were taking HAART prior to stroke onset. CD4 count
was available in 37 patients; 21 had CD4 200 cells/mm3 and 16
had CD4 B 200 cells/mm3 (mean CD4 count 329.7 cells/mm3).
Conclusion: HIV infection increases the risk of stroke in younger
patients. They have lower blood pressure, HDL and NIH stroke scale
on admission compared to HIV negative stroke patients. Prevalence
of DM, HTN, hyperlipidemia and other metabolic factors were not
significantly different in the two groups, although the relatively small
sample size and retrospective nature of the study represent limiting
factors.
B22 - AIDS-related Kaposi’s sarcoma (KS),
lymphoma, cervical and anal carcinoma
including Human Herpes Virus 8 infection
(HHV8)
Results of Significant Characteristics
WEAB0204
Characteristic
Age-Mean (Range)
Male sex-no (%)
HIV Positive
HIV Negative
p
Group(N43)
Group (N 101)
Value
57.8 (4180)
32 (74.4%)
71.6 (3499)
45 (44.6%)
Caucasian
11 (45.8%)
72 (72.7%)
African American
13 (54.2%)
14 (14.1%)
Race
Asian
NIHSS on admission
Systolic Blood
0.001
0.007
0.001
0 (0%)
13 (13.1%)
5.39
9.09
142.18
158.19
0.03
0.018
40.72
47.71
0.043
Pressure on
Admission
HDL (mg/dl)
HPV genotype attribution of anal neoplasia in HIV-positive
MSM: estimating the preventable fraction and disease
misclassification
V. Sahasrabuddhe1, P. Castle2, S. Follansbee3, S. Borgonovo3,
B. LaMere3, D. Tokugawa3, T. Darragh4, S. Boyle5, M. Sadorra5,
S. Tang5 and N. Wentzensen1
1
National Cancer Institute, Division of Cancer Epidemiology and
Genetics, Rockville, United States. 2American Society for Clinical
Pathology, Washington, United States. 3Kaiser Permanente Northern
California, San Francisco, United States. 4University of California at
San Francisco, San Francisco, United States. 5Roche Molecular
Systems, Pleasanton, United States
Presenting author email: vikrant.sahasrabuddhe@nih.gov
Background: To further our understanding of anal lesions in relationship to HPV genotypes in HIV-infected men who have sex with men
(MSM), we analyzed HPV genotype distribution in anal disease
Table 1. Potential range of vaccine protection in a cross-sectional study of n363 HIV-infected MSM: attribution schemes for
AIN2/3* lesions to HPV genotypes in prophylactic HPV vaccines
Prevalence of HPV vaccine genotypes in AIN2/3 lesions
Hierarchical attribution fraction
Cases with single
Genotypes in bivalent HPV vaccine:
of AIN2/3 to HPV vaccine
carcinogenic HPV type1
Cases with any HPV type2
genotypes3
36.7% (95% CI: 21.954.5)
61.8% (95% CI: 52.570.3)
56.4% (95% CI: 47.065.3)
40.0% (95% CI: 24.657.7)
70.0% (95% CI: 60.977.8)
56.4% (95% CI: 47.065.3)
86.7% (95% CI: 70.394.7)
92.7% (95% CI: 86.396.3)
89.1% (95% CI: 81.993.7)
HPV16/18
Genotypes in quadrivalent HPV vaccine:
HPV16/18/6/11
Genotypes in nonavalent HPV vaccine:
HPV16/18/6/11/31/33/45/52/58
*AIN2/3: refers to a diagnosis using a combined cytologic-histologic endpoint of AIN2 (AIN2 histology or HSIL-AIN2/ ASC-H cytology) or AIN3
(AIN3 histology or HSIL-AIN3 cytology); this does not refer to a histologic classification of ‘‘AIN2/3’’ (or moderate to severe dysplasia) which
would be classified as AIN3 (based on automatic default to the more severe disease category in case of dual/intermediate disease classification).
1
Genotypes from cases in whom only a single carcinogenic type is detected, irrespective of additional possible/non/unknown carcinogenic types
(n 30 cases of HO cases of AIN2/3).
2
Genotypes from cases in whom arty HPV type was detected (n l09 cases of 110 cases of AIN2/3).
3
in ‘Hierarchical attribution’, HPV genotypes are attributed proportionally to the case by the most frequent type (according to hierarchical
frequencies in the AIN2/3 category), This allows attribution of HPV genotypes to the disease category regardless of multiplicity of infections.
51
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
Figure 1. Unsupervised hierarchical clustering of AIN disease categories (various cytology-histology combinations) by distribution of
carcinogenic HPV gentypes.
categories based on cytology and histology results. Knowledge of HPV
genotype attribution can allow estimation of the preventable fraction
of anal intraepithelial neoplasia (AIN) and may indicate disease
misclassification.
Methods: 363 HIV-infected MSM underwent anal cytology
and high-resolution anoscopy/biopsy at an anal cancer screening
clinic. Anal disease categories were determined by combining
histology and anal cytology results. We evaluated presence of HPV
genotypes by Linear Array and estimated preventable fractions of
anal lesions based on attribution to genotypes included in bivalent,
quadrivalent, and nonavalent HPV vaccines. We explored classification of histology-cytology disease groups based on distribution
of carcinogenic HPV genotypes using unsupervised hierarchical
clustering.
Results: The proportion of carcinogenic HPV infections increased
from 51.4% in MSM without AIN to 98.2% in those with AIN3.
HPV16 was the most common HPV genotype overall (28.1%) and
among MSM with AIN2/3 lesions (51.8%). The attribution fractions of
AIN2/3 to genotypes included in HPV vaccines ranged from
56.4% (95% CI: 47.065.3) for the bivalent vaccine to 89.1% (95%
CI: 81.993.7) for the nonavalent vaccine. (Table) In the exploratory
clustering analysis, the disease group of normal histology/HSIL
cytology and AIN1histology/HSIL cytology clustered with AIN2/AIN3
on histology based on the distribution of carcinogenic HPV types.
(Figure).
Conclusion: A substantial fraction of high grade AIN can be prevented
by prophylactic HPV vaccines. Both anal cytology and high resolution
anoscopy followed by anal biopsy and histology have limited sensitivity
for prevalent anal precancer. We demonstrate that combined histology-cytology disease categories can improve misclassification in
cross-sectional studies. Our analytical framework can be useful to
compare attribution of anal disease categories to HPV genotypes
across various populations and to estimate the extent of disease
misclassification.
B23 - Clinical trials - phase I/II
TUAB0102
Once-daily maraviroc in combination with ritonavir-boosted
atazanavir in treatment-naı̈ve patients infected with
CCR5-tropic HIV-1 (study A4001078): 96-week results
A. Mills1, D. Mildvan2, D. Podzamczer3, G. Fätkenheuer4, M. Leal5,
S. Than6, S.R. Valluri7, C. Craig8, M. Vourvahis7, J. Heera6, H. Valdez7,
T. Brown9, A. Rinehart10 and S. Portsmouth7
1
Anthony Mills MD Inc., Los Angeles, United States. 2Beth Israel
Medical Center Division of Infectious Diseases, New York, United
States. 3HIV Unit, Infectious Disease Service, Hospital Universitari de
Bellvitge, Barcelona, Spain. 4First Department of Internal Medicine,
University Hospital of Cologne, Köln, Germany. 5Infectious Disease
Service, Virgen del Rocio University Hospital, Seville, Spain. 6Pfizer
Inc., Groton, United States. 7Pfizer Inc., New York, United States.
8
Pfizer Inc., Sandwich, United Kingdom. 9Division of Endocrinology
and Metabolism, Johns Hopkins University, Baltimore, United States.
10
ViiV Healthcare, Research Triangle Park, United States
Presenting author email: tmills@tonymillsmd.com
Background: Maraviroc (MVC) is a CCR5 antagonist approved
for the treatment of CCR5-tropic (R5) HIV-1. This study evaluated a
once-daily (QD), dual-therapy regimen of MVC plus atazanavir/
ritonavir (ATV/r) in treatment-naı̈ve patients; 96-week outcomes are
presented.
Methods: In this Phase 2b, randomized, open-label study, 121 R5
HIV-1-infected patients received either MVC 150 mg QD (n60) or
tenofovir/emtricitabine (TDF/FTC) 200/300 mg QD (n 61) with
ATV/r 300/100 mg QD for 48 weeks, later extended to 96 weeks. The
primary endpoint was the proportion of patients with HIV-1
RNA B50 copies/mL at Week 48.
52
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Results: At Week 96, the proportion of patients with HIV-1 RNA B50
andB400 copies/mL was 67.8% (40/59) and 78.0% (46/59),
respectively, for MVC versus 82.0% (50/61) and 83.6% (51/61),
respectively, for TDF/FTC. Protocol-defined treatment failure occurred in 5 patients (MVC: n 3; TDF/FTC: n 2). Median change
from baseline in CD4 count was similar for both arms (MVC: 269
cells/mm3; TDF/FTC: 305 cells/mm3). Median change from baseline
in creatinine clearance was 5.5 mL/min for MVC and 18 mL/min
for TDF/FTC. Five patients (MVC: n 4; TDF/FTC: n1) had plasma
HIV-1 RNA 500 copies/mL at failure or study discontinuation;
virologic analyses detected no resistance, change in tropism or
loss of susceptibility relevant to treatment in either arm. At
Week 48, there was a greater reduction in immune activation on
CD4 cells in patients receiving MVC versus TDF/FTC. Markers of
bone formation were significantly different between arms at both 48
and 96 weeks.
Conclusion: Durable virologic activity of MVC 150 mg QDATV/r was
demonstrated through 96 weeks, with no differences between the
arms in the rates of virologic failure, no resistance or change in
tropism seen, and with most of the treatment difference due to lowlevel transient viremia. Differences between the arms in immune
activation and bone markers require further investigation.
B24 - Clinical trials - phase III/post-licensing
Track B Clinical Science
(ATV/co) and 87% (ATV/r) (difference: 2.2%; 95% CI: 7.4 to 3.0)
(Table 2); among subjects with HIV-1 RNA 100,000 copies/mL, the
response rates were similar (86 vs 86%). Two subjects in ATV/co and
none in ATV/r group developed resistance mutations to study drugs;
both were M184V/I. Similar percentages of subjects in both
groups (ATV/co vs ATV/r) had serious adverse events (AEs) (11 vs
7%), discontinued study drug due to any AEs (7 vs 7%), or had
bilirubin-related AEs (4 vs 3%). Median increases in total bilirubin at
Week 48 in ATV/co and ATV/r group were 1.9 and 1.7 mg/dL.
Median increases in serum creatinine were 0.13 and 0.09 mg/dL.
Median increases in total cholesterol were 4 and 10 mg/dL; increases
in triglycerides were 16 and 24 mg/dL. Plasma exposures of
ATV (steady state mean Ctau [ng/mL]) were comparable (796.1 vs
853.4).
Conclusion: ATV/co was noninferior to ATV/r in combination with
TDF/FTC at Week 48. Both regimens achieved high rates of virologic
success. Safety and tolerability profiles of the two regimens were
comparable.
ATV/co (n344) ATV/r (n348)
Age (years), median
36
Male
Race-White
HIV-1 RNA (log10copies/mL),
median
HIV-1 RNA 100,000 copies/mL
CD4 count (cells/mm3), median
83%
58%
4.78
TUAB0103
CD4 count 5200 cells/ mm3
Cobicistat versus ritonavir as pharmacoenhancers in
combination with atazanavir plus tenofovir disoproxil
fumarate/emtricitabine: phase 3 randomized, double blind,
active-controlled trial, week 48 results
Baseline Characteristics.
J. Gallant1, E. Koenig2, J. Andrade-Villanueva3, P. Chetchotisakd4,
E. Dejesus5, F. Antunes6, K. Arastéh7, G. Moyle8, G. Rizzardini9,
J. Fehr10, Y.-P. Liu11, L. Zhong11, C. Callebaut11, S. Ramanathan11,
J. Szwarcberg11, M. Rhee11 and A. Cheng11
1
Johns Hopkins School of Medicine, Baltimore, United States.
2
Instituto Dominicano de Estudios Virologicos - IDEV-, Santo
Domingo, Dominican Republic. 3Hospital Civil, Guadalajara,
Mexico. 4Khon Kaen University, Muang District, Thailand. 5Orlando
Immunology Center, Orlando, United States. 6Hospital de
Santa Maria, Lisboa, Portugal. 7EPIMED/Vivantes Auguste-ViktoriaKlinikum, Berlin, Germany. 8Chelsea & Westminster Hospital, London,
United Kingdom. 9Ospedale Luigi Sacco, Milano, Italy. 10University
Hospital Zurich, Zurich, Switzerland. 11Gilead Sciences, Foster City,
United States
Snapshot Analysis
Snapshot Analysis (Per Protocol)
Time to Loss of Virologic
Response
Missing Failure
Missing Excluded
Background: Cobicistat is a novel investigational pharmacoenhancer
with no anti-HIV activity.
Methods: An international, randomized, double-blind, doubledummy, active controlled trial was conducted to evaluate the
efficacy and safety of cobicistat vs ritonavir as pharmacoenhancers
of atazanavir (ATV/co vs ATV/r group) in combination with tenofovir
disoproxil fumarate (TDF)/emtricitabine (FTC) in treatment-naı̈ve
patients. Key eligibility criteria were HIV-1 RNA ]5,000 copies/mL,
estimated glomerular filtration rate by Cockcroft-Gault formula
(eGFR)]70 mL/min. Primary endpoint was HIV-1 RNA B50 copies/
mL at Week 48 by snapshot algorithm, and noninferiority margin
was 12%.
Results: A total of 692 subjects were randomized and received at
least 1 dose of study drug (344 in ATV/co group and 348 in ATV/r
group) (Table 1). At Week 48, virologic success was achieved in 85%
38%
348
17%
37
83%
62%
4.84
41%
341
16%
ATV/co (n344) ATV/r (n348)
85%
98%
83%
87%
98%
85%
89%
97%
90%
96%
Efficacy at Week 48 (HIV-1 RNA B50 copies/mL).
TUAB0104
SPIRIT study: switching to emtricitabine/rilpivirine/
tenofovir df (FTC/RPV/TDF) single-tablet regimen (STR) from
a ritonavir-boosted protease inhibitor and two nucleoside
reverse transcriptase inhibitors (NRTIS) maintains HIV
suppression and improves serum lipids in HIV-1-positive
subjects
F. Palella1, P. Tebas2, B. Gazzard3, P. Ruane4, D. Shamblaw5, J. Flamm6,
M. Fisher7, J. van Lunzen8, R. Ebrahimi9, K. White9, B. Guyer9,
H. Graham9 and T. Fralich9
1
Northwestern University, Feinberg School of Medicine, Chicago,
United States. 2University of Pennsylvania, Division of Infectious
Diseases, Clinical Trials Unit, Philadelphia, United States. 3Chelsea
and Westminster Hospital Foundation Trust, London
United Kingdom. 4Peter J. Ruane, MD, Inc., Los Angeles, United
States. 5La Playa Medical Group and Clinical Research, San Diego,
United States. 6Kaiser Permanente, Sacramento, United States.
7
Brighton and Sussex University Hospitals, Brighton, United Kingdom.
53
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
8
9
Track B Clinical Science
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Gilead Sciences, Foster City, United States
Background: Antiretroviral regimen simplification improves both
quality of life, and long-term medication adherence while reducing
the risk of HIV virologic failure (VF) and long-term drug-related
toxicities. FTC/RPV/TDF is a well-tolerated, once daily STR treatment
option. This is the first study to evaluate the efficacy and safety of
switching from boosted Protease Inhibitor (PI) based HAART to a
simplified regimen of FTC/RPV/TDF STR.
Methods: A randomized, open-label, multi-center, international, 48
week study to evaluate the safety and efficacy of switching from
ritonavir-boosted PI regimens to FTC/RPV/TDF in virologicallysuppressed (HIV RNA B50 copies/mL), HIV-1 infected subjects.
Participants were randomized 2:1 to switch to FTC/RPV/TDF or
maintain their current PI-based regimen. The primary endpoint was
non-inferiority (12% margin) of FTC/RPV/TDF relative to PI-based
regimens in maintaining plasma HIV-1 RNA B50 copies/mL at Week
24 by Snapshot analysis. Changes in serum lipids from baseline were
evaluated.
Results: A total of 476 subjects were randomized and received at
least 1 dose of study drug (317 FTC/RPV/TDF; 159 PI). Baseline
characteristics were similar (Table 1). Switching to FTC/RPV/TDF
was non-inferior to maintaining a ritonavir-boosted PI regimen
(93.4% versus 89.9%) at Week 24 for HIV RNA B50 copies/mL
(95% CI [ 2.0%, 8.9%]). Fewer subjects in the FTC/RPV/TDF arm
than the PI arm had virologic failure by Snapshot, defined as HIV
RNA ]50 copies/mL at Week 24 or discontinuations of study
drug with HIV RNA ]50 copies/mL (1.3% vs 5.0%). Two subjects
in the FTC/RPV/TDF arm had emergent resistance and one in
the PI arm. Overall total cholesterol, LDL, and triglycerides
decreased to a greater extent among FTC/RPV/TDF than PI
recipients (Table 2).
Males (%)
Black or African Heritage (%)
Age (mean, years)
CD4 (mean, cells/mm3)
FTC/RPV/TDF
PI
86.1
19.2
41
576
90.6
13.8
43
600
Baseline Demographics.
Mean Change
at Week 24
Baseline
Total Cholesterol
(mg/dL)
LDL (mg/dL)
Triglycerides
(mg/dL)
HDL (mg/dL)
Total Cholesterol/
HDL
FTC/RPV/
TDF
PI
FTC/RPV/
TDF
192
194
25
121
163
124
173
16
53
53
3.86
50
4.08
4
0.27
PI
p value
1 B0.001
0
3
B0.001
B0.001
1 B0.001
0.08 B0.001
Fasted Serum Lipids and Change from Baseline at We.
Conclusion: Switching to the FTC/RPV/TDF STR from a ritonavirboosted PI regimen in virologically-suppressed, HIV-1-infected participants maintains virologic suppression with low risk of virologic
failure while improving total cholesterol, LDL, and triglycerides.
TUAB0105
Efficacy and safety results from a randomized, double blind,
active controlled trial of elvitegravir (once-daily) versus
raltegravir (twice-daily) in treatment-experienced
HIV-positive patients: long term 96-week data
R. Elion1, J.-M. Molina2, J.-R. Arribas-Lopez3, D. Cooper4,
F. Maggiolo5, E. Wilkins6, B. Conway7, Y.-P. Liu8, L. Zhong8, N. Margot8,
J. Szwarcberg8, M. Rhee9 and A. Cheng8
1
Whitman-Walker Health, Washington, United States. 2Hopital Saint
Louis, Service des Maladies infectieuses, Paris, France. 3Hospital
Universitario La Paz, Servicio de Medicina Interna, Unidad VIH,
Madrid, Spain. 4Kirby Institute, University of New South Wales,
Sydney, Australia. 5Ospedali Riuniti di Bergamo, Bergamo, Italy.
6
North Manchester General Hospital, Manchester, United Kingdom.
7
Vancouver ID Research & Care Centre, Vancouver, Canada. 8Gilead
Sciences, Foster City, United States. 9Gilead Sciences, HIV Clinical
Research, Foster City, United States
Presenting author email: relion@wwc.org
Background: Once-daily elvitegravir (EVG) was noninferior in efficacy
and well-tolerated relative to twice-daily raltegravir (RAL) in
combination with a fully active ritonavir-boosted protease inhibitor
(PI/r) and another second agent in a phase 3 study of treatmentexperienced patients (GS-US-183-0145) at Week 48. We present the
blinded 96-week results.
Methods: Randomized, double-blinded, active-controlled, 96-week
noninferiority trial. Key eligibility criteria were HIV-1 RNA ]1,000
copies/mL, any CD4 cell count, and resistance to and/or 6 months’
experience with at least two classes of antiretroviral drugs. Primary
endpoint was achievement and maintenance of HIV-1 RNA B50
copies/mL through Week 48 (time to loss of virologic response
[TLOVR] analysis).
Results: All 712 randomized and treated subjects (EVG: 354, RAL: 358)
were included for safety evaluation; 702 of 712 (EVG: 351, RAL: 351)
for efficacy evaluation (10 subjects were excluded due to protocol
violation). At Week 96, 47.6% in EVG and 45.0% in RAL group were
suppressed (difference 2.6% [95% CI: 4.6 to 9.9]) (Table). Mean
increases in CD4 cell count (cells/mm3) were similar in EVG and RAL
group (205 vs. 198). Nine subjects died while receiving study drug (2
in EVG and 7 in RAL group). Similar percentages in EVG and RAL group
reported serious adverse events (AEs) (20.1 vs. 23.5%), grade 3 or 4
AEs (24.3 vs. 23.7%), or discontinued study drug due to AEs (3.1 vs.
4.2%). Grade 3 or 4 AST and ALT elevations ( 5 ULN) were less
common on EVG vs. RAL (2.3 vs. 5.9%; 1.7 vs. 5.3%). No other
differences in graded laboratory abnormalities were seen.
TLOVR
Virologic response
Virologic failure
Death
Drug discontinuation
Adverse events
Lack of efficacy
Lost to follow-up
Other reasons
Emerging major INSTI
resistance
EVG (n351)
RAL (n351)
47.6%
22.8%
0.6%
26.5%
2.6%
3.7%
5.4%
17.4%
6.6%
45.0%
27.4%
2.6%
20.8%
4.3%
2.0%
6.8%
12.0%
7.4%
Efficacy at Week 96 (HIV-1 RNA B50 copies/mL)
Conclusion: At Week 96, once-daily EVG in combination with a fully
active PI/r and another second agent in treatment-experienced
54
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
patients continue to be noninferior to twice-daily RAL in efficacy
with excellent tolerability. These data support the long-term use of
EVG in treatment-experienced patients.
Virologic response
EVG
RAL
Missing=Failure
Missing=Excluded
53.6% (188/351)
79.0% (188/238)
56.4% (198/351)
83.2% (198/238)
Efficacy at Week 96 (HIV-1 RNAB50 copies/mL).
THLBB04
Once-daily dolutegravir (DTG; S/GSK1349572) is non-inferior
to raltegravir (RAL) in antiretroviral-naive adults: 48 week
results from SPRING-2 (ING113086)
F. Raffi1, A. Rachlis2, H.-J. Stellbrink3, W.D. Hardy4, C. Torti5, C. Orkin6,
M. Bloch7, D. Podzamczer8, V. Pokrovsky9, S. Almond10, D. Margolis11
and S. Min11, The SPRING-2 Team
1
University of Nantes, Nantes, France. 2Sunnybrook & Women’s
College Health Sciences Centre, Toronto, Canada. 3IPM Study Center,
Hamburg, Germany. 4Cedars-Sinai Medical Center, Los Angeles,
United States. 5Azienda Ospedaliera Spedali Civili, Brescia, Italy.
6
Royal London Hospital, London, United Kingdom. 7Holdsworth
House Medical Practice, Darlinghurst, Australia. 8Hospital Universitari
de Bellvitge, Barcelona, Spain. 9Russian Federal Guidance Centre of
AIDS, Moscow, Russian Federation. 10GlaxoSmithKline, Mississauga,
Canada. 11GlaxoSmithKline, Research Triangle Park, United States
Presenting author email: francois.raffi@wanadoo.fr
Background: The integrase inhibitor, Dolutegravir (DTG; S/
GSK1349572), has shown rapid and durable antiviral response, with
a favorable tolerability profile.
Methods: In this multicenter, double-dummy-blinded, Phase III, noninferiority study, HIV-1 infected ART-naive adults with HIV-1 RNA
]1000 c/mL and no evidence of viral resistance were randomized
1:1 to receive DTG 50 mg QD or RAL 400 mg BID, in addition to
investigator-selected backbone NRTIs of either TDF/FTC or ABC/3TC.
Subjects were stratified by screening HIV-1 RNA ( 5 and 100,000
c/mL) and backbone NRTI selection. The primary endpoint was
proportion of subjects with HIV-1 RNA B50 c/mL through Week 48
(FDA ‘‘snapshot’’ algorithm).
Results: 827 subjects were randomized (DTG n413, RAL n414).
At baseline: median age 36 years, 14% female, 15% non-white, 28%
HIV-1 RNA 100,000 c/mL, 41% ABC/3TC. Proportion of subjects
meeting the primary endpoint was 88% for DTG and 85% for RAL;
difference (2.5%; 95% CI: 2.2% to 7.1%) met 10% non-inferiority
criteria. For subjects with HIV-1 RNA 100,000 c/mL, response
rate was 82% for DTG vs 75% for RAL. Secondary analyses supported
non-inferiority: HIV-1 RNA B50 c/mL per-protocol (DTG 90% vs
RAL 88%), treatment-related discontinuation failure (93% vs 92%)
and virologic non-response (5% vs 8%). Median CD4 increases
were similar (230 cells/mm3 each). Most commonly reported
( ]10%) adverse events (AEs) were nausea (DTG 14%, RAL 13%),
headache (12% each), nasopharyngitis (11%, 12%) and diarrhea (11%
each). Discontinuation due to AEs was 2% in each group. At virologic
failure, there was no genotypic integrase or NRTI resistance in
the DTG group vs 1 subject and 4 subjects, respectively, in the RAL
group.
Conclusion: At week 48, once-daily DTG was non-inferior to twicedaily RAL in treatment-naive HIV-1 infected subjects, with no
evidence of emergent resistance to DTG in virologic failure. DTG
plus NRTIs could be an option for first-line HIV treatment.
B25 - Cohort studies
THPDB0103
Assessing the WHO recommended first-line ART regimens
for resource-limited settings: comparing the relative
virologic efficacy and resistance patterns of TDF/3TC/NVP to
AZT/3TC/NVP in a Rwandan cohort
J.-C. Karasi1,2, F. Musonera2, K. Iranyumviye2, J.-Y. Servais1,
C. Devaux1, A. Binagwaho3, V. Arendt1, R. Shafer4, A. Zolopa4 and
J.-C. Schmit1
1
CRP-Santé, Retrovirology Laboratory, Luxembourg-Ville,
Luxembourg. 2Rwanda Biomedical Center, National Reference
Laboratory, Kigali, Rwanda. 3Ministry of Health, Kigali, Rwanda.
4
Division of Infectious Diseases, Stanford University, San Francisco,
United States
Presenting author email: karasirw@me.com
Background: AZT/3TC/NVP and TDF/3TC/NVP BID have been recommended 1st-line ART regimens in Rwanda. TDF/3TC/NVP is the least
well studied of the WHO-recommended 1st-line regimens. We
compared the efficacy of this regimen with AZT/3TC/NVP.
Methods: Between 2009 and 2011, we enrolled ART-naive patients.
CD4 counts (cells/ul) and viral load (VL) were collected before ART
and at 26 and 52 weeks. The primary endpoint was a VLB200
copies/ml by week 52 using an ITT analysis. Genotypic resistance
testing (GRT) was performed on samples with VL 1000 copies/ml.
Results: 1,072 HIV ART-naive patients were enrolled: 521 (48.6%)
received AZT/3TC/NVP (AZT), 551 (51.4%) received TDF/3TC/NVP
(TDF). Median age was 37; 64% were women. Median baseline CD4
count was similar 260, VL was 100,000 copies/ml in 43% (AZT) vs.
32% (TDF) (p B 0.001). The AZT versus TDF, 5.4% vs. 3.8% transferred
to others health facilities, 3.6% vs. 4.0% were lost to follow-up, and
1.9% vs. 2.7% died. 10%(AZT) vs 4%(TDF) of discontinued therapy due
to adverse effects (p0.001). The primary endpoint were: 80% (441/
551) TDF and 78% (410/521) receiving AZT attained a VL B200
copies/ml by week 52. The median CD4 count increase was 88 in the
AZT and 50 in the TDF groups (p0.034). However, in patients with
baseline VL 100,000 copies/ml, 44% (133/351) in the TDF vs. 56%
(170/351) in the AZT group attained the primary endpoint (p 0.001).
11.8% (TDF) and 7.7% (AZT) underwent GRT. 58% had 1 NNRTIresistance mutation: most commonly Y181C (34%) and K103N (16%).
53% had 1 NRTI-resistance mutation: most commonly
M184V (48%) and K65R (29%). K65R emerged exclusively in the TDF
group.
Conclusion: TDF/3TC/NVP was as effective as AZT/3TC/NVP at
attainingB200 copies/ml by week 52. However, it was less effective
in patients with higher baseline VL and was associated with a lesser
CD4 count increase.
B28 - Antiretroviral drug resistance
TUAB0302
Similar prevalence of baseline HIV-1 minority variants
among responders and virologic failures, as well as
increased detection of HIV-1 minority variants at treatment
failure, in rilpivirine patients from the ECHO and THRIVE
Phase III studies (post hoc resistance analysis)
L. Rimsky1, V. Van Eygen1, J. Vingerhoets1, K. Thys1, J. Aerssens1,
M. Stevens1 and G. Picchio2
55
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
1
Janssen Infectious Diseases BVBA, Beerse, Belgium. 2Janssen
Research & Development LLC, Titusville, United States
Background: In the ECHO and THRIVE studies (HIV-1 treatmentnaive patients), rilpivirine (RPV) 25mg qd and efavirenz (EFV) 600mg
qd plus background N(t)RTIs resulted in a 78% response rate
(viral load [VL] B50 copies/mL; ITT-TLOVR) at Week 96. However,
the overall incidence of virologic failure (VF) was higher for RPVtreated than for EFV-treated patients. The impact of baseline HIV-1
minority variants on and their emergence in VF to RPV was
investigated.
Methods: Ultra-deep sequencing (UDS, llIumina Inc.) and Sanger
population-sequencing (SPS) were performed on a representative
Table 1. Proportion of RPV patients with baseline NNRTI or
N(t)RTI RAMs detected as rrinority variants by UDS
RPV VF N 47
RPV responder N 49
NNRTI RAMs
8 (17)
6 (12)
V189I*
3 (6)
0
V90I
1 (2)
V106I
2 (4)
2 (4)
V1081*
1 (2)
0
V179I
1 (2)
1 (2)
V179D*
F227C*
0
0
1 (2)
1 (2)
N(t)RTI RAMs
2 (4)
0
M184V*
1 (2)
0
L210W*
1 (2)
0
n, (%)
*RAM not previously identified at baseline by SPS. RPV RAMS are
underlined.
Table 2. Proportion of RPV VF patients with NNRTI or N(t)RTI
RAMs: at failure detected as irinority variants by UDS
n, (%)
RPV VF N43
NNRTI RAMs
29 (60)
V90I
11 (23)
V189I
8 (17)
H221Y
7 (15)
K101E
6 (13)
E138K
5 (10)
V179I
V10SI
4 (8)
3 (6)
2 (4)$
L100I, V106A, V108I, or E138R$
$
$
$
K101Q , E138G , E138Q, F227C, Y188H ,
G190E/ or M230L
N(t)RTI RAMs
$
1 (2)$
16 (33)
K219E
4 (8)
Ml841
3 (6)
D67N
K65R, K70E$, or L210W$
2 (4)$
A62V, V75I, or Ml84V
1 (2)$
RAM not prevmuily identified at failure SPS.
Each RAM was observed ind span dentin at the reported
prevalence. RPV RAMS are underlined.
$
subset of RPV VF patients (baseline and failure) and RPV responder
patients. HIV-1 minority variants were defined as those with NNRTI
or N(t)RTI resistance-associated mutations (RAMs) detected by UDS
but not by SPS. Linkage analysis was done by matching sequence
reads through positional information.
Results: At baseline (Table 1), minority variants with NNRTI RAMs
were detected in 17% RPV VF-patients and 12% RPV responderpatients (p 0.57), and with N(t)RTI RAMs in 4% and 0% (p0.24),
respectively. None of the baseline NNRTI RAMs found in RPV VF
patients were associated with RPV resistance.
At failure (Table 2), UDS revealed that RPV VF-patients carried a
variety of additional NNRTI RAMs (including RPV RAMs) and
N(t)RTI RAMs not detected by SPS. Furthermore, minority variants
carrying NNRTI/N(t)RTI RAMs were identified in 4/12 (33%)
RPV VF-patients with no RAMs by SPS. Linkage analysis demonstrated
that in the RPV VF-patients, E138K and K101E were mutually exclusive,
and E138K (or K101E) was usually linked to M184I or M184V.
Conclusion: In conclusion, the prevalence at baseline of minority
variants carrying NNRTI and/or N(t)RTI RAMs was low and comparable
between responders and VF patients treated with rilpivirine. Although
at failure no new RPV RAMs were identified by UDS, minority
variants carrying NNRTI/N(t)RTI RAMs were present in a subset of
patients failing RPV without any detectable mutations by SPS.
TUAB0303
Changing patterns of NRTI and PI resistance mutations
between 2006 and 2011 in 1,200 ART-experienced South
African patients: association with the introduction of
tenofovir (TDF) and abacavir (ABC) and with the cumulative
effects of LPV/r therapy
G. van Zyl1, M. Claassen2, S. Engelbrecht1, T. de Oliveira3, W. Preiser1,
N. Wood4, S. Travers4 and R. Shafer5
1
National Health Laboratory Service & Stellenbosch University,
Pathology (Medical Virology), Cape Town, South Africa. 2National
Health Laboratory Service (NHLS), Pathology (Medical Virology), Cape
Town, South Africa. 3Africa Centre for Health and Population Studies,
University of KwaZulu-Natal, Mtubatuba, South Africa. 4South African
National Bioinformatics Institute (SANBI), University of Western
Cape, Cape Town, South Africa. 5Stanford University Medical Center,
Division of Infectious Diseases, Center for AIDS Research, Stanford,
United States
Presenting author email: guvz@sun.ac.za
Background: In 2009, South Africa’s National AIDS Council recommended TDF access to HIV adults and ABC to HIV infants/
children. We analyzed the effects of these guideline changes on
NRTI-resistance mutations in ART virological failure (VF) and analyzed
the effect of the cumulative second-line LPV/r use on emerging PI
resistance.
Methods: HIV RT and PR sequences were obtained from plasma
samples submitted for genotypic resistance testing to the Tygerberg
National Health Service Laboratory between 2006 and 2011 from
patients experiencing ART VF. Demographic and ART treatment data
were obtained from the physicians submitting samples.
Results: Between 2006 and 2011, 1,525 plasma samples were
obtained from 1,293 patients, of whom 57% were female and
42%B15 years old. 99% of viruses were subtype C. TDF use
increased from B2% of patients between 20062008 to 40% in
2011 and ABC use fromB10% between 20062008 to 41% in 2011.
K65R occurred in 33 (31%) of 105 TDF/3TC/EFV recipients, 7 (88%) of
8 TDF/3TC/NVP recipients, and 2 (7%) of 28 TDF/3TC/LPV/r
recipients. L74V occurred in 22 (44%) of 50 ABC/3TC/EFV recipients,
2 (50%) of 4 ABC/3TC/NVP recipients, and 4 (6%) of 71 ABC/3TC/LPV/
56
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
r recipients. Of 439 patients receiving an LPV/r-containing regimen,
42 (10%) had 1 of the following major PI-resistance mutations:
V32I, M46I, I47A, I50V, I54V, L76V, V82A/F, I84V, and L90M. 17 (4%)
of 42 LPV/r recipients had major DRV/r resistance mutations (V32I,
I50V, and L76V).
Conclusion: The increased use of TDF and ABC since 2009 has been
associated with a markedly increased frequency of TDF-resistance
(K65R) and ABC-resistance (L74V). Compared with TDF/3TC/EFV
recipients, the risk of developing K65R was higher in patients with
TDF/3TC/NVP VF (88% vs 31%; p 0.002) and lower in patients with
TDF/3TC/LPV/r VF (7% vs 31%; p0.008). Among 439 LPV/r recipients,
42 (10%) had LPV/r resistance and 17(4%) DRV/r cross-resistance.
Track B Clinical Science
efavirenz (EFV) for the treatment of HIV-TB co-infected
patients: results of the ANRS 12 180 Reflate TB trial
C. Charpentier, R. Landman, C. Laouénan, V. Joly, G. Hamet,
F. Damond, F. Brun-Vézinet, F. Mentré, D. Descamps and P. Yeni
Hopital Bichat - Claude-Bernard, Paris, France
Presenting author email: charlotte.charpentier@bch.aphp.fr
B. Grinsztejn1, N. De Castro2,3, V. Arnold4, V. Veloso1, M. Morgado5,
J.H. Pilotto6, C. Brites7, J.V. Madruga8, N. Barcellos9, B. Riegel
Santos10, C. Vorsatz1, C. Grondin4, M. Santini-Oliveira1, O. Patey11,
C. Delaugerre2,3, G. Chêne4, J.-M. Molina2,3 and ANRS 12 180 Reflate
TB study group
1
Instituto de Pesquisa Clinica Evandro Chagas, Fiocruz, Laboratório
de Pesquisa Clı́nica em DST/AIDS, Rio de Janeiro, Brazil. 2University of
Paris Diderot, Sorbonne, Paris Cité, INSERM U941, Paris, France.
3
Hospital Saint-Louis, AP-HP, Paris, France. 4University Bordeaux,
INSERM U897, Bordeaux, France. 5Instituto Oswaldo Cruz-FIOCRUZ,
Laboratory of AIDS and Molecular Immunology, Rio de Janeiro, Brazil.
6
Hospital Geral de Nova Iguaçu, Departamento de DST/AIDS, Nova
Iguaçu, Brazil. 7Hospital Universitário Prof. Edgar Santos, Laboratório
de Pesquisa em Doenças Infecciosas, Salvador, Brazil. 8Centro de
Referência e Treinamento DST/AIDS, Unidade de Pesquisa, São Paulo,
Brazil. 9Health State Secretariat Hospital Sanatório Partenon, Porto
Alegre, Brazil. 10Hospital Nossa Senhora da Conceição, Serviço de
Infectologia, Porto Alegre, Brazil. 11C.H.G Villeneuve St George,
Department of Internal and Tropical Medicine, Villeneuve St George,
France
Presenting author email: nathalie.de-castro@sls.ap-hop-paris.fr
Background: Since the availability of viral load (VL) assay with a
threshold of 20 copies/mL, some patients display VL values between
20 and 50 copies/mL. The aims of our study were to: (i) identify
factors associated with low level viremia (LLV) in patients receiving
stable suppressive antiretroviral therapy (cART); and (ii) assess
virological outcome during the year following LLV detection.
Methods: Retrospective study among the 4820 patients followed in
our institution fulfilling the inclusion criteria: (i) stable cART for at
least 6 months; (ii) all VLB50 copies/mL; and (iii) at least 3 VL
determinations during a one-year period. We compared patients
with all VLB20 copies/mL (Group LLV-) and patients with at least
2 VL between 20 and 50 copies/mL (Group LLV). ‘‘Blip Ratio’’
was defined as: (number of VL 50 copies/mL)/(number of VL
determinations) before study inclusion.
Results: Among the 656 patients included, 5.8% were in group LLV.
The nature of the ongoing cART did not differ between LLV- and
LLV groups. In the multivariate analysis, only CDC clinical stage B/C
at study inclusion (OR 2.9; 95% CI 1.45.9; P 0.003) and a
higher ‘‘Blip Ratio’’ before study inclusion (OR 0.9; 95%
CI 0.91.0; P0.001) were independently associated with LLV.
During the follow-up, the proportion of patients experiencing
virological failure (2 consecutive VL 50 copies/mL) was not
different between LLV- and LLV groups (4% vs 8%, respectively;
P 0.32); and 40% of patients shifted from LLV to LLV- status.
Conclusion: LLV was infrequent in our series and the one-year followup did not evidence a higher rate of virological failure than in patients
always fully-suppressed. LLV seems to be a transient phenomenon
that might be driven by residual ongoing viral replication and/or viral
release and/or accuracy of VL assay in lower values.
Background: Alternatives to EFV for the treatment of HIV-infection in
patients with TB are warranted. Rifampin decreases RAL exposure in
healthy volunteers. We estimated the safety and efficacy of two
doses of RAL and EFV in HIV-1-infected adults receiving rifampin
for TB.
Methods: Multicentre, open-label, randomized, phase II trial. Antiretroviral naı̈ve HIV-1-infected adults were randomized to receive
RAL (400 or 800 mg bid) or EFV (600 mg qd),in combination with TDF
and 3TC, after starting rifampin. The primary efficacy end-point was
the proportion of patients with plasma HIV-RNA level B50 cp/ml at
week 24 using a mITT TLVOR algorithm. The sample size was
calculated to compare success rate in each arm to 70%. Safety was
assessed by the report of adverse events using the ANRS grading
scale.
Results: From July 2009 to June 2011, 179 patients were screened
and 155 randomized to RAL 800 (n52), RAL 400 (n 51) and EFV
(n 52). At baseline, 73% were male, mean age: 38 yrs, median HIVRNA level: 4.9 log10 cp/ml and median CD4 cell count:140cells/mm3.
At week 24 success rates were 78% [95% CI, 6790], 76%
[95% CI, 6588] and 63% [95% CI, 4976] in RAL800, RAL400 and
EFV arms, respectively(mITT TLOVR).Plasma HIV RNA 50cp/ml was
the main reason for failure and occurred in 6,11 and 16 patients in
RAL800,RAL400 and EFV,respectively. There was a trend towards
more RAL,3TC, and TDF resistance in the RAL400 than RAL800 arm.
Safety of the three regimens was good with only 1,1 and 3 grade 3/4
ALT elevations in RAL800, RAL400 and EFV arms, respectively.
Conclusion: At week 24, RAL800 mg bid provided the highest success
rate in HIV-1-infected patients receiving a rifampin-based therapy for
TB and should be considered for further evaluation.
WEPDB0102
Persistent low-level HIV-1 RNA between 20 and 50 copies/
ml in antiretroviral treated patients: associated factors and
virological outcome
B29 - Pharmacology, pharmacokinetics and
pharmacogenomics, role of therapeutic
drug monitoring, drug interactions
THLBB01
A randomized multicentre open-label trial to estimate the
efficacy and safety of two doses of raltegravir (RAL) to
TUPDB0101
Atazanavir pharmacokinetics and efficacy and safety
outcomes by sex in AIDS Clinical Trials Group Study 5202
(A5202)
C. Venuto1,2, K. Mollan3, Q. Ma2, E. Daar4, P. Sax5, M. Fischl6,
A. Collier7, K. Smith8, D. Lu3, C. Tierney3, G. Morse2 and ACTG 5202
Protocol Team
1
University of Rochester, Center for Human Experimental
Therapeutics, Rochester, United States. 2University at Buffalo,
57
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Buffalo, United States. 3Harvard School of Public Health, Center for
Biostatistics in AIDS Research, Boston, United States. 4Harbor-UCLA
Medical Center, Division of HIV Medicine, Los Angeles, United States.
5
Brigham and Women’s Hospital, Harvard Medical School, Boston,
United States. 6University of Miami School of Medicine, Miami,
United States. 7University of Washington at Harborview Medical
Center, Seattle, United States. 8Rush University Medical Center,
Chicago, United States
Presenting author email: charles.venuto@chet.rochester.edu
Background: A5202 was a randomized equivalence study of four daily
regimens of efavirenz (EFV) or atazanavir/ritonavir (ATV/r) with
double-blinded tenofovir and emtricitabine or abacavir and lamivudine. Previous findings from A5202 reported women assigned ATV/r
had higher-risk of virologic failure (VF) than women assigned EFV;
also, women on ATV/r had higher risk of VF than men on ATV/r. This
analysis relates ATV clearance (CL) to treatment efficacy and safety.
Methods: The associations between ATV CL and times to VF and
safety event (first increased grade 3/4 sign, symptom, or laboratory
abnormality), while on ATV/r (as-treated), were estimated with
hazard ratios (HR) from Cox proportional hazards models, adjusted
for screening HIV-1 RNA (B105 or 105 copies/mL) and NRTIs.
Additionally adjusted models included race-ethnicity (RE), age,
baseline CD4 count, and body mass index. Interactions between
ATV CL and sex, RE, and NRTIs were evaluated. A 1-compartment
pharmacokinetic (PK) model including 815 subjects (88% of 928
randomized to ATV/r) was used to estimate subject-specific ATV CL.
Atazanavir CL was categorized by overall sample tertiles (slow: B7;
¯ 9 L/hr). Analyses were restricted
intermediate: 7 to B9; and rapid to 768 subjects of white, black, or Hispanic RE.
Results: Atazanavir CL association with time to VF differed significantly by sex (p 0.003, Table 1). The association between ATV CL
and time to VF did not differ significantly by NRTIs (p 0.6) or RE
(p 0.085); additionally adjusted model results were similar.
There was no significant association between ATV CL and time to
safety event (rapid vs. intermediate: HR 1.06; 95% confidence
interval (0.79, 1.43); slow vs. intermediate: HR 1.28 (0.95, 1.72),
p0.22), nor a significant interaction with sex, NRTIs or RE for this
outcome (p]0.31).
ATV Clearance Association with time to VF
N768: 131 females (28 VFs), 655 males (78 VFs)
Comparison
Rapid (n38) vs. Intermediate (n 29)
among Female
Slow (n 64) vs. Intermediate among
Female
Rapid (n249) vs. Intermediate (n210)
among Male
Slow (n196) vs. Intermediate among Male
Hazard Ratio (95%
Confidence Interval)
3.49 (1.249.84)
0.82 (0.262.54)
1.50 (0.822.71)
2.10 (1.163.77)
*ATV CL by Sex Interation: p0.003.
Conclusion: The differential in CL association with time to VF by sex
may reflect PK/pharmacodynamic reasons for failure, and will require
further investigations.
Track B Clinical Science
D. Haas1, E. Acosta2, S. Vardhanabhuti3, H. Ribaudo3, P. Severe4,
U. Lalloo5, N. Kumarasamy6, F. Taulo7, J. Kabanda8, O. Oneko9,
P. Ive10, P. Sambarey11, E. Chan3, J. Hitti12, D. McMahon13 and for the
AIDS Clinical Trials Group
1
Vanderbilt University, Nashville, United States. 2University of
Alabama at Birmingham, Birmingham, United States. 3Statistical Data
Analysis Center, Harvard School of Public Health, Boston, United
States. 4Groupe Haitien d’Etude du Sarcome de Kaposi et des
Infections Opportunistes (GHESKIO), Port-au-Prince, Haiti. 5Nelson R.
Mandela School of Medicine, University of KwaZulu Natal, Durban,
South Africa. 6YRGCARE Medical Centre, VHS, Chennai, India.
7
Malawi College of Medicine, Johns Hopkins University Research
Project, Blantyre, Malawi. 8Joint Clinical Research Centre, Kampala,
Uganda. 9Kilimanjaro Christian Medical Centre, Moshi, United
Republic of Tanzania. 10University of Witwatersrand, Helen Joseph
Hospital, Johannesburg, South Africa. 11BJ Medical College, Pune,
India. 12University of Washington, Seattle, United States. 13University
of Pittsburgh, Pittsburgh, United States
Presenting author email: david.w.haas@vanderbilt.edu
Background: Nevirapine (NVP) is metabolized by cytochrome
P450 (CYP) 2B6. We investigated associations between single
nucleotide polymorphisms (SNPs), haplotypes, and pharmacokinetics
(PK) following SD NVP to prevent mother-to-child transmission
(MTCT).
Methods: Protocol A5207 evaluated strategies to prevent
NVP resistance following intrapartum SD NVP. At onset of labor,
participants received SD NVP (200 mg) and were randomized to
lamivudine/zidovudine, emtricitabine/tenofovir, or lopinavir/ritonavir (LPV/r), for 7 or 21 days. Plasma for NVP assay was obtained at
post-partum day 1 and week 1, 3 and 5. Derived PK parameters
included the NVP elimination constant estimated using linear mixed
effect models based on natural logarithm of NVP measured between
day 1 and week 3. We assayed 214 SNPs in ABCB1, CYP2B6, CYP2C19,
CYP3A4, CYP3A5 and NR1I2. CYP2B6 metabolizer status was based on
*6/*18 haplotypes. SNP and CYP2B6 haplotype associations were
based on parametric regression models adjusted for body mass index
and treatment arm as indicated.
Results: In A5207, 422 women in Haiti, India, Malawi, South Africa,
Tanzania, and Uganda received SD NVP at onset of labor. This analysis
includes 304 women (217 and 87 of African and Indian descent,
respectively) with suitable NVP assay and genotype data. Among
individuals of African descent, CYP2B6 metabolizer status was
associated with slower NVP elimination (p 0.045), but not
with week 5 NVP BLQ (below limit of quantification). Median
elimination constants were 0.0105 (*6/*6, *6/*18 or *18/
*18*), 0.0108 (*6/ or *18/ ), and 0.0113 ( / ) h 1.
Among these individuals on LPV/r, an ABCB1 SNP (rs7787082) was
associated with slower NVP elimination (p 0.0046). Among Indians,
an NR1I2 SNP (rs2472682) was associated with increased likelihood
of week 5 NVP BLQ (p 0.0061).
Conclusion: Slow metabolizer CYP2B6 genotypes were associated
with slower elimination following SD NVP. This association appeared
less pronounced than that described at steady state, suggesting
effects on gene inducibility. Non-CYP2B6 SNP associations may be
spurious.
TUPDB0104
TUPDB0102
A single nucleotide polymorphism in CYP2B6 leads
to 3-fold increases in efavirenz concentrations in
intensive pharmacokinetic curves and hair samples
Pharmacogenetics of intrapartum single-dose nevirapine
(SD NVP) in AIDS Clinical Trials Group (ACTG) Protocol
A5207
M. Gandhi1, R. Greenblatt2, P. Bacchetti3, C. Jin3, M. Cohen4,
J. Dehovitz5, K. Anastos6, S. Gange7, C. Liu8, S. Hanson9, B. Aouizerat9
and Women’s Interagency HIV Study (WIHS)
58
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
1
University of California at San Francisco, Medicine, San Francisco,
United States. 2University of California at San Francisco, Clinical
Pharmacy, San Francisco, United States. 3University of California
at San Francisco, Epidemiology and Biostatistics, San Francisco,
United States. 4Rush University Medical Center, Medicine
Chicago, United States. 5SUNY Downstate Medical Center,
Medicine, Brooklyn, United States. 6Albert Einstein College of
Medicine, Medicine, Bronx, United States. 7Johns Hopkins
Bloomberg School of Public Health, Baltimore, United States.
8
Georgetown University, Medicine, Washington, United States.
9
University of California at San Francisco, Nursing, San Francisco,
United States
Presenting author email: monica.gandhi@ucsf.edu
Background: Prior studies investigating pharmacogenomics and
efavirenz exposure use single plasma drug levels, which are limited
by marked day-to-day variability. The Women’s Interagency HIV Study
(WIHS) performed 24 hour pharmacokinetics (PK) studies in a large
number of HIV-infected women on efavirenz and calculated areasunder-the-curve (AUC) as measures of short-term exposure; concentrations in hair assessed long-term exposure. We typed 183 single
nucleotide polymorphisms (SNPs) in 9 candidate genes known to
influence efavirenz absorption, distribution, metabolism and elimination (ADME) and examined them in relation to AUC and hair levels
in multivariate models.
Methods: Intensive PK studies were conducted in 111 women (74%
African American; 17% Hispanic; 9% white). SNPs (n 183) with a
minor allele frequency of 0.05 were analyzed in CYP2B6, CYP2C19,
CYP3A4/A5, ABCB1, ABCC2, CYP2D6, SCL22A6, UDP, and UGT1A,
along with other factors that could influence PK (race, age, menstrual
status, diet, liver and renal function, weight). Hair efavirenz levels
were measured in 84 women. Variables were examined with logtransformed EFV AUC and hair levels via linear regression; multivariable models were constructed by forward stepwise selection,
including non-genetic predictors with p-valuesB 0.05 and genetic
predictors with p-valuesB 0.001.
Results: Non-genetic factors, such as transaminase levels and
orange juice consumption, were associated with EFV AUCs, but the
most significant predictors associated with exposure were
CYP2B6 516GT, CYP2B6 983TC and a p-glycoprotein transporter
(ABCB1) haplotype (Table). CYP2B6 516TT (12.6% prevalence) was
associated with 3.5-fold (95% CI 2.74.5, p8.6x10 19) increases
in AUC and 3.2-fold (2.14.7, p1.3x10 11) increases in hair
concentrations.
Conclusion: A comprehensive search for SNPs in genes associated
with efavirenz ADME demonstrated that CYP2B6 516TT was
associated with 3-fold increases in short-term (AUC) and longterm (hair) EFV exposure. The effect of this SNP on exposure over the
prolonged duration represented by hair levels is reported for the first
time. Genetic testing may allow optimization of EFV dosing.
Genetic and non-genetic factors associated with short-term EFV exposure (AUC, n111)
Factor
Effect on AUC (995% CI)
p-value
Distribution of factor
Oranges or orange juice in preceding 5 days
1.26 (1.051.50)
0.0119
76 (68.5%)
For every doubling of ALT level
1.23 (1.111.36)
0.0001
Median ALT (range)
23 (8117) IU/L
CYP2B6 983 T C (rs28399499)
0 doses of minor allele (TT)
1 or 2 doses of minor allele (TC/CC)
2.210 10
2 doses of minor allele (TT)
ABCB1 hdplotype (2SNPs:rs7779562 &rs4148745)
0 doses of the haplotype
1 or 2 doses of the haplotype
16(14.4%)1 dose
1.410 18
CYP2B6 516 G T (rs3745274)
0 or 1 dose of minor allele (GG, GT)
95 (85.6%)0 dose
1.00
1.96 (1.542.5)
97 (87.4%)0/1 dose
1.00
3.5 (2.7 4.5)
14(12.6%)2 doses
0.0004
1.00
14 (12.6%)0 dose
1.60 (1.242.1)
97 (87.4%)1/2 doses
Factors associated with long-term exposure (hair levels, n 84) -models include adherence
Factor
Effect on hair (995% CI)
p-value
Distribution of factor
ALT, Orange juice, ABCB1 haplotype, and adherence (below) not significantly associated with hair levels
CYP2B6 983 T C ( rs28399499)
0 doses of minor allele (TT)
1 or 2 doses of minor allele (TC/CC)
0.021
1.70 (1.092.7)
10 (11.9%)1/2 doses
1.010 10
CYP2B6 516 G T (rs3745274)
0 or 1 dose of minor allele (GG, GT)
2 doses of minor allele (TT)
74 (88.1%) 0 dose
1.00
71 (84.5%) 0/1 dose
13 (15.5%)2 doses
1.00
3.2 (2.14.7)
Self-reported adherence
574%
1.00
7594%
0.94 (0.451.96)
0.88
13 (15.4%)
]95%
1.10 (0.562.2)
0.77
67 (79.8%)
4 (4.8%)
Hair EFV PG table.
59
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
TUPDB0105
Comparison of the in vivo pharmacokinetics and in vitro
dissolution of raltegravir tablets in HIV-positive patients
given the drug by swallowing or by chewing
C. Gervasoni1, S. Baldelli1, M. Cerea2, P. Meraviglia1, S. Landonio1,
M. Simioni1, A. Gazzaniga2, M. Galli2, G. Rizzardini1, E. Clementi2 and
D. Cattaneo1
1
Luigi Sacco Hospital, Milano, Italy. 2Università degli Studi di Milano,
Milano, Italy
Presenting author email: cristina.gervasoni@unimi.it
Background: The pharmacokinetics of raltegravir in HIV-1 infected
subjects is characterized by high inter/intra-patient variability. We
investigated the potential contribution of the drug pharmaceutical
formulation on raltegravir pharmacokinetics.
Methods: We firstly compared in vivo the pharmacokinetics of
raltegravir from 50 patients given the drug by swallowing with those
obtained from 10 HIV-infected patients that chewed raltegravir due
to swallowing difficulties. Subsequently we evaluated in vitro the
dissolution of raltegravir tablets under different conditions (pH 1, pH
6.8 buffer and water). Dissolution tests were performed comparing
raltegravir whole tablets with tablets crushed by grinding in mortar
and pestle.
Results: In the in vivo study we found that the raltegravir pharmacokinetic profiles in patients given the drug by swallowing were highly
variable, characterized in some cases by multiple peaks and irregular/
limited absorption. Conversely, patients given raltegravir by chewing
presented regular pharmacokinetic profiles, characterized by single
sharp drug peak and higher raltegravir absorption compared with
patients given the drug by swallowing (Figure 1).
The in vitro studies showed that the whole tablets presented
relatively slow release profiles due to lacking disintegration. Crushed
tablets tested in water and pH 6.8 buffer exhibited prompt and
complete dissolution of raltegravir. For whole tablets tested in the
acidic medium the raltegravir concentrations were very low, reaching
less the 10% of the dose after 2h, owing to well-known poor
solubility of raltegravir at low pH. However, when crushed tablets
were tested in acid the profiles presented significantly higher
concentrations of raltegravir (Figure 2).
Conclusion: HIV-infected patients given raltegravir by chewing
showed higher drug absorption compared with patients given the
drug by swallowing. This may be depends to problems related to the
tablets disintegration leading to erratic drug release. The improvement of the raltegravir pharmaceutical formulation could reduce
Figure 1. Raltegravir time-concentration profiles in HIV-patients
given the drug by swalling or chewing.
Figure 2. In vitro dissolution profiles of whole tabletes versus
crushed tablets of raltegravir at different pH.
variability of raltegravir pharmacokinetics, eventually contributing to
increase the response of HIV-infected patients.
B31 - When to start therapy?
THLBB05
Effect of early versus delayed initiation of antiretroviral
therapy (ART) on clinical outcomes in the HPTN 052
randomized clinical trial
B. Grinsztejn1, M. Hosseinipour2, S. Swindells3, H. Ribaudo4, J. Eron5,
Y.Q. Chen6, L. Wang6, S.-S. Ou6, M. Anderson6, M. McCauley7,
T. Gamble8, N. Kumarasamy9, J. Hakim10, J. Kumwenda11, J. Pilotto12,
S. Godbole13, S. Chariyalertsak14, B. Santos15, K. Mayer16,
S. Eshleman17, E. Piwowar-Manning18, L. Cottle6, J. Makhema19,
L. Mills20, R. Panchia21, I. Sanne22, V. Elharrar23, D. Havlir24,
M.S. Cohen5 and for the HPTN 052/ACTG Study Team
1
Instituto de Pesquisa Clinica Evandro Chagas, Fiocruz, Rio de Janeiro,
Brazil. 2UNC Project Malawi and University of North Carolina at
Chapel Hill, Lilongwe, Malawi. 3University of Nebraska Medical
Center, Omaha, United States. 4Center for Biostatistics in AIDS
Research, Harvard School of Public Health, Boston, United States.
5
University of North Carolina School of Medicine, Chapel Hill, United
States. 6Vaccine and Infectious Disease Division, Fred Hutchinson
Cancer Research Center, Seattle, United States. 7FHI 360,
Washington, DC, United States. 8FHI 360, Durham, United States.
9
YRG CARE Medical Centre, Chennai, India. 10University of
Zimbabwe, Department of Medicine, Harare, Zimbabwe. 11College of
Medicine Johns Hopkins Project, Blantyre, Malawi. 12Hospital Geral
de Nova Iguau and Laboratorio de AIDS e Imunologia Molecular-IOC,
Rio de Janeiro, Brazil. 13National AIDS Research Institute (ICMR),
Pune, India. 14Research Institute for Health Sciences, Chiang Mai
University, Chiang Mai, Thailand. 15Hospital Nossa Senhora da
Conceiao, Porto Alegre, Brazil. 16Fenway Health/Harvard Medical
School, Boston, United States. 17Johns Hopkins School of Medicine,
Department of Pathology, Baltimore, United States. 18Johns Hopkins
60
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
052 WTS LB-K-M and table.
University School of Medicine, Department of Pathology, Baltimore,
United States. 19Botswana Harvard AIDS Institute, Gaborone,
Botswana. 20KEMRI-CDC Research and Public Health Collaboration,
CDC Division of HIV/AIDS Prevention, Kisumu, Kenya. 21Perinatal HIV
Research Unit (PHRU), University of the Witwatersrand,
Johannesburg, South Africa. 22University of Witswatersrand,
Department of Medicine, Johannesburg, South Africa. 23National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, Bethesda, United States. 24University of California - San
Francisco, San Francisco, United States
Presenting author email: beatriz.grinsztejn@gmail.com
Background: To inform optimal timing of ART initiation, we analyzed
clinical outcomes during follow-up of HPTN 052 incorporating both
AIDS and non-AIDS events related to HIV and ART.
Methods: HIV adults (CD4350 550/mL) from Africa, Asia, and
South America were randomized to ART immediately or after
CD4 B250/mL or AIDS (delayed). Primary clinical events were:
death, WHO Stage 4, tuberculosis, severe bacterial infection, serious
cardiovascular/vascular disease, serious liver disease, end stage renal
disease, non-AIDS malignancy, and diabetes mellitus. Secondary
events were: WHO Stage 2/3, malaria, renal insufficiency, hepatic
transaminitis, lipodystrophy, dyslipidemia, hypertension, peripheral
neuropathy, lactic acidosis, and thrombocytopenia. Distributions of
time to first clinical event were estimated using Kaplan-Meier
method; treatment comparisons used log-rank tests. Incidence rates
were estimated by arm (with 95% confidence intervals); robust
standard errors accommodated repeated events.
Results: 1761 participants accrued 4038 person years follow-up (FU);
median FU of 2.1 years; median CD4 at ART initiation was 230/mL
and 442/mL in the delayed and immediate arms. 134 individuals
experienced at least one primary clinical event, including 26 deaths
and 21 non-AIDS events. Compared to immediate ART, delayed ART
was associated with shorter time to first primary clinical event
(P0.07), AIDS-defining disease (P 0.03), and tuberculosis
(P0.02); also higher incidence of tuberculosis (1.8, 95% CI [1.3,
2.6]/100 PY versus 0.8, [0.5, 1.3]/100 PY, P0.009) and all targeted
clinical events (29.0, [26.3, 31.9]/100PY versus 24.7, [22.3, 27.3]/
100PY; P 0.02) (Figure). Sensitivity analysis excluding pre-specified
secondary events (recurrent upper respiratory tract infections,
unexplained weight loss [moderate and severe], unexplained chronic
diarrhea, unexplained persistent fever, unexplained anemia, lipodystrophy and hypertension) showed a consistent result (19.9, [17.8,
22.2]/100PY versus 14.4, 12.6, 16.4]/100PY; P0.0003 in the
delayed versus immediate arms).
Conclusion: In HIV adults with CD4 350550/mL, immediate
versus delayed ART significantly reduced the incidence of clinical
events, notably tuberculosis, AIDS-defining events, and WHO Stage
2/3 clinical events.
B32 - First line therapy
THPDB0104
Antiretroviral therapy outcomes measured by virologic
failure in Nigeria
P.J. Kanki1, C. Chang1, S. Meloni1, H. Rawizza2, T. Jolayemi3,
B. Banigbe-Aluko3, P. Okonkwo3 and Harvard/APIN PEPFAR team
1
Harvard School of Public Health, Immunology and Infectious
Disease, Boston, United States. 2Brigham & Women’s Hospital,
Boston, United States. 3AIDS Prevention Initiative In Nigeria, Ltd./
Gte., Abuja, Nigeria
Presenting author email: pkanki@hsph.harvard.edu
61
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Background: Nigeria’s population of over 150 million and HIV
prevalence of 3.8% ranks it among the top 5 countries with the
highest HIV burden. Since 2004, HRSA has provided PEPFAR support
to Harvard/APIN to develop a HIV prevention, care and treatment
program at 32 hospitals in Nigeria.
Methods: ART eligibility in the adult program is consistent with the
Nigerian and WHO ART guidelines. Enrolled patients that gave
written informed consent with greater than 6 months of ART were
included in this study. Patients had clinical exams and laboratory
tests, at baseline, month 3, 6, and every 6 months thereafter. All
patient data was collected and stored electronically. Treatment
failure was defined as 2 consecutive viral loads 1000 copies/mL
following 6 months on ART.
Results: As of December 2010, 76,269 adult patients were enrolled
on ART, 60,600 (79.5%) of which were ARV-naı̈ve at baseline. Nine
tertiary hospitals accounted for the majority of patients (53,406;
88.4%) with the remainder at 23 secondary. Female patients were
more common (64.3%) and younger compared to men (median age
32 versus 39 years). Median baseline CD4 was 143 cells/mm3 and VL
was 68,731 copies/mL. First-line ART for treatment-naı̈ve patients
included zidovudine (AZT) (51.6%), tenofovir (TDF) (35.3%) or
stavudine (d4T) (7.5%) plus lamivudine/emtricitabine (3TC/FTC) plus
an NNRTI - nevirapine (NVP) (68.4%)/efavirenz (EFV) (26%). The
cumulative virologic failure rate for naı̈ve patients was 21.4%, with
the majority of failures occurring in the first year (56.9%). Applying
the revised 2010 WHO recommendation defining virologic failure at
5000 copies/mL, the cumulative failure rate was 13.6%, with
55.8% of failures in the first year.
Track B Clinical Science
Background: The second-line ART was rolled out in India in 2009 at
10 centers. Patients meeting immunologic/clinical failure criteria
were evaluated by an expert panel and underwent viral load testing.
Those found to have a confirmed virologic failure (VL 5,000c/mL)
were started on second-line ART (zidovudine/tenofovir/lamivudine/
lopinavir/ritonavir). We evaluated 18-month outcomes of patients
started on second-line treatment.
Methods: Patients seen monthly and CD4 was performed every 6
months. VL testing was conducted 6 months after second-line ART
initiation. We performed multivariable logistic regression modeling
to determine factors associated with 6-month virologic suppression
( B400 c/mL) and mortality at 12 months.
Results: Between January and June 2010, 411 patients initiated
second-line ART in the national programme. At treatment switch,
median CD4 count was 82 cells/mm3, and median VL was 83,000 c/
mL. After 6 months of second-line ART, 374 (91%) patients remained
alive and on treatment, and of survivors, 79% achieved virologic
suppression. At 12 and 18 months after second-line ART initiation,
362 (88%) and 306 (75%) patients remained alive and in care,
respectively. Among survivors, median CD4 count increase at 18
months was 227 cells/mm3. Male sex (adjusted odds ratio (aOR) 2.8,
95% confidence interval (CI) 1.17.2), and baseline hemoglobin B10
g/dL (aOR 4.0, 95% CI 2.08.2) were associated with failure to
achieve virologic suppression at 6 months. The presence of WHO
clinical failure criteria at treatment switch (adjusted odds ratio (aOR)
3.6, 95% confidence interval 1.4 -9.2) was associated with increased
risk for death at 12 months.
Conclusion: Despite advanced disease at the time of treatment
switch, patients achieved good immunologic and survival outcomes
after 18 months of second-line ART. Patients with clinical failure were
at increased risk for death, highlighting the importance of routine
immunologic and if feasible, virologic monitoring in first-line ART for
earlier detection of treatment failure.
B35 - Management of late presenters
THAB0303
Virologic failure by time on ART.
Conclusion: Virologic failure rates were highest in the first year of
ART and decreased with duration of ART. Particular emphasis on drug
adherence and retention in care during the first year of ART may
optimize patient outcomes.
B33 - Second line therapy
THPDB0105
High rates of survival, virologic suppression and immune
reconstitution among patients receiving second-line
antiretroviral therapy in the Indian national programme
B.B. Rewari1, M. Shaukat2, S. Kabra1 and P. Srikantiah3
1
National AIDS and STD Control Organization, New Delhi, India.
2
National AIDS Control Organisation, Ministry of HFW, New Delhi,
India. 3University of California, HIV/AIDS Division, San Francisco,
United States
Presenting author email: drbbrewari@yahoo.com
Characteristics of individuals presenting late for care across
Europe: results from the Collaboration of Observational HIV
Epidemiological Research Europe (COHERE)
J. Lundgren1,2 and on behalf of the late presenters working group of
the Collaboration of Observational HIV Epidemiological Research in
Europe
1
University of Copenhagen, Copenhagen HIV Programme,
Copenhagen, Denmark. 2Rigshospitalet, Copenhagen, Denmark
Presenting author email: jdl@cphiv.dk
Background: A large proportion of individuals enter health care very
late in the course of their HIV-infection, these individuals have a poor
clinical prognosis. This analysis aims to investigate trends in the
percentage of individuals presenting late for care and identify factors
associated with late presentation.
Methods: Individuals enrolled in the Collaboration of Observational
HIV Epidemiological Research Europe (COHERE), which includes 33
cohorts from across Europe, who presented for care for the first time
after 1st January 2000 were included. Late presentation was defined,
as a person presenting for care with a CD4 count B350 cells/mL or an
AIDS defining event. Logistic regression was used to identify factors
associated with late presentation.
Results: Of the 90,786 individuals included, 47,384 (52.2%) were
classified as late presenters, of those 28,869 (60.9%) presented with
advanced disease (a CD4 count B200 cells/mL or an AIDS defining
62
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
Table 1. Characteristics of 90,786 individuals presenting for care in Europe after 1st January 2000
Individuals not presenting late
Total presenting for care (N, % of total)
43402
47.8
Individuals presenting late
47384
52.5
Mode of infection (N, %)
MSM*
20800
47.9
14988
31.6
Heterosexual Male
Heterosexual Female
6126
9313
14.1
21.5
11369
11761
24.0
24.8
Male DU
5.7
2079
4.8
2695
Female IDU
814
1.9
825
1.7
Male other 2973
6.8
3898
8.2
Female other 1297
3.0
1848
3.9
Europe
17922
41.29
17196
36.2
Africa
4320
9.95
7822
16.5
Other
2697
6.21
3439
7.3
18463
42.54
18927
39.9
Region of origin (N, %)
Unknown
Age (Median, IQR)
CD4 count, cells/mm3(Median, IQR)
34
2841
37
3145
540
435694
180
73271
*MSM: Men who have sex with men, DU: Injection drug use,
Other mode of infection: includes haemophiliac, transfusion not haemophilia related, other and unknown.
event). The table gives the characteristics of individuals presenting
for care and the figure shows the percentage of individuals with
late presentation and advanced disease by year of HIV diagnosis.
The odds of presenting late decreased only minimally over time
(odds ratio [OR] 0.97 per year, 95% confidence-interval 0.970.98,
pB.0001). Individuals who were older (OR 1.35 per 10 years,
1.371.41, pB 0.0001), whose mode of transmission was not MSM,
particularly heterosexual males (OR 2.08 compared to MSM,
2.002.17, p B.0001), and those originating from Africa (OR 1.67,
1.591.75, pB.0001), or other regions (OR 1.40, 1.331.48,
pB.0.0001) compared to Europe, were more likely to present late
for care.
Conclusion: Around one half of HIV-1 positive individuals
across Europe are presenting late for care. Individuals who are
older, from regions other than Europe and heterosexual males are
more likely to present late. These populations need to be specifically
targeted to reduce the number of individuals presenting late for
care.
Figure 1. The percentage of individuals classfied as late presenters and the median CD4 count in all those presenting for care by calender year.
63
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
5
B39 - Pharmacokinetics, pharmacodynamics, pharmacogenomics, therapeutic drug monitoring, formulations,
drug interactions in children and
adolescents
MOAB0202
Lipoprotein lipase genetic variant P- was associated with
lower risk of hypertriglyceridemia in children after one year
of HAART
C. Colombero1, C. Rocco1, D. Mecikovsky2, R. Bologna2, P. Aulicino3,
L. Sen3 and A. Mangano3
1
Hospital de Pediatrı́a JP Garrahan, Lab. Biologı́a Celular y Retrovirus,
Ciudad de Buenos Aires, Argentina. 2Hospital de Pediatrı́a JP
Garrahan, Servicio de Infectologı́a, Ciudad de Buenos Aires,
Argentina. 3Hospital de Pediatrı́a JP Garrahan, CONICET, Lab. Biologı́a
Celular y Retrovirus, Ciudad de Buenos Aires, Argentina
Presenting author email: amangano@garrahan.gov.ar
Background: Lipoprotein Lipase (LPL) is a key enzyme in lipid
metabolism, especially for plasma circulating triglycerides (TG).
Genetic variants of LPL have been associated to lipid levels in
healthy individuals, cardiovascular disease, obesity and diabetes.
Our aim was to evaluate the influence of three polymorphisms: Hind
III (intron 8), Pvu II (intron 6) and S447X (exon 9) in plasma TG levels
in HIV-1 infected children under HAART.
Methods: 52 children (28 girls and 24 boys) diagnosed with HIV-1
between 2005 and 2009, were retrospectively selected with at least
one plasma TG level assessment. Also, 86 seronegative blood donors
were randomly selected to estimate allelic frequencies in Argentinean population. TG levels were examined before and after one-year
of HAART. Hypertriglyceridemia was defined as TG 150 mg/dL.
Hind III (H/H), Pvu II (P/P ) and S447X (S/X) were
determined by PCR-RFLP. Wilcoxon sum rank test was used to
compare median plasma TG among groups.
Results: Allelic frequencies for HIV-1 infected children were: H-,0.21
P-, 0.53 and X: 0.05, with no significant difference to controls. After
one year of HAART, median TG levels were significantly lower in
P/P (144 mg/dL) and P /P (95 mg/dL) compared to P/P
(180 mg/dL) (p 0.03 and p 0.0002, respectively). A gene dosedependent effect was observed for P- allele, and its presence was
associated with a 7-fold lower risk of hypertriglyceridemia. Additionally, when H-is accompanying P-, the risk diminished to 15-fold
(p 0.008, OR 0.06, 95% CI B0.010.63).
Conclusion: Our findings suggest a protective effect of LPL polymorphisms against hypertriglyceridemia in children after one-year of
HAART. A long-term effect of these variants are under studied. These
results could endorse a prompt nutritional or pharmacological
intervention in patients lacking the P- allele.
TUAB0201
Tenofovir disoproxil fumarate (TDF) pharmacokinetics (PK)
with daily dosing in the first week of life (HPTN 057)
K. Nielsen-Saines1, M. Mirochnick2, N. Kumwenda3, E.C. Joao4,
R. Kreitchmann5, J. Pinto6, B. Santos7, T. Parsons8, P. Richardson8,
T. Taha3, L. Mofenson9, P. Sato10, B. Kearney11 and M.G. Fowler12
1
David Geffen School of Medicine at UCLA, Los Angeles, United
States. 2Boston University, Boston, United States. 3Johns Hopkins
Bloomberg School of Public Health, Baltimore, United States.
4
Hospital dos Servidores do Estado, Rio de Janeiro, Brazil.
Irmandade da Santa Casa de Misercordia de Porto Alegre, Porto
Alegre, Brazil. 6Universidade Federal de Minas Gerais, Belo
Horizonte, Brazil. 7Grupo Hospitalar Conceicao, Porto Alegre, Brazil.
8
Johns Hopkins University School of Medicine, Baltimore, United
States. 9NICHD/PAMAB, Bethesda, United States. 10NIAID, Bethesda,
United States. 11Gilead Sciences, Forest City, United States. 12Johns
Hopkins Medical Institutes, Kampala, Uganda
Presenting author email: knielsen@mednet.ucla.edu
Background: There are limited data on the pharmacokinetics (PK) of
tenofovir (TFV) administered to pregnant women during labor or to
newborns.
Methods: HPTN 057 is a phase I trial of tenofovir disoproxil fumarate
(TDF) in HIV-infected pregnant women and their neonates in Malawi
and Brazil. In the current cohort, women received 600 mg TDF at
labor onset or 4 hours prior to C section (C/S) and newborns
received 6 mg/kg TDF suspension daily 7 doses. Plasma samples
were obtained from mothers at delivery, from cord blood and from
infants before and 2, 10 and 24 hours after the 1st, 4th and 7th doses.
TFV concentration (conc) was determined by HPLC/MS/MS; lower
limit of quantitation was 5 ng/mL. The PK target was to keep infant
TFV conc 50 ng/ml (mean trough conc in nonpregnant adults) for
the first week of life. Data are presented as median (range) or
geometric mean (%CV).
Results: 33 mother-infant pairs were studied (21 vaginal deliveries,
12 C/S). Delivery occurred median of 4.5 (0.611.4) hours after
dosing. Mean maternal TFV conc at delivery was 108 (76.1%) ng/mL.
Mean cord blood TFV conc was 61 (69.3%) ng/mL. Cord blood TFV
conc was50 ng/mL in 24/31 (77%). Mean ratio of cord blood to
maternal delivery TFV conc was 0.55 (64.0%). Infant 24 hr postdose
conc was50 ng/mL in 28/31 (90.3%) after the first dose, in 27/28
(96.4%) after the 4th dose and in 22/30 (73.3%) after the 7th dose.
All infant TFV conc were 30 ng/mL. All mothers and infants
tolerated TDF well.
Mean (CV%) infant PK parameters are presented below:
Dose Cmax(ng/mL) C24h(ng/mL) AUC(ng*hr/mL)
1
4
7
288 (49.9%)
336 (40.5%)
221 (66.1%)
104 (47.9%)
112 (52.1%)
69.7 (45.7%)
3939 (37.6%)
4413 (37.4%)
3060 (49.0%)
t½ (hrs)
13.2 (80.1%)
14.5 (45.0%)
14.6 (96.1%)
Mean (CV%) infant PK parameters.
Conclusion: This regimen provides TFV exposure similar to adults
receiving 300 mg daily doses and is appropriate for use in neonates
in studies of TDF used for HIV prophylaxis or treatment.
TUAB0203
Pharmacokinetics, safety and efficacy of dolutegravir (DTG;
S/GSK1349572) in HIV-1-positive adolescents: preliminary
analysis from IMPAACT P1093
R. Hazra1, R. Viani2, E. Acosta3, N. Zheng4, C. Alvero4, E. O’Gara5,
E. Petzold6, B. Heckman7, D. Steimers8, I. Song8, S. Piscitelli8,
A. Wiznia9 and P1093 Study Team
1
NIH/NICHD, Pediatric Adolescent and Maternal AIDS Branch,
Bethesda, United States. 2University of California San Diego School of
Medicine, La Jolla, United States. 3University of Alabama at
Birmingham School of Medicine, Birmingham, United States.
4
Harvard School of Public Health, Boston, United States. 5NIH/NIAID,
International Maternal, Adolescent and Pediatric Branch, Bethesda,
United States. 6Social & Scientific Systems, Durham, United States.
7
Frontier Science and Technology Research Foundation, Inc.,
Amherst, United States. 8GlaxoSmithKline, Research Triangle Park,
64
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
United States. 9Jacobi Medical Center, Bronx, United States
Presenting author email: hazrar@mail.nih.gov
Background: P1093, is an ongoing, Phase 1/2 open-label PK, safety
dose finding study of DTG plus optimized background regimen
(children 6 wks to B18 yrs) in age defined cohorts. Selected pediatric
doses will be those providing comparable PK exposure to those
observed at 50mg once daily in adults with acceptable pediatric
safety/tolerability.
Methods: Children ]12 to B18 yrs were enrolled to evaluate DTG
weight-based fixed doses at 1.0 mg/kg once daily. Intensive PK
evaluation, over 24 hours, following observed dose (Days 510) after
DTG was added to stable, failing ARV regimen (or started as
monotherapy, those not currently taking ARV). Background therapies
were optimized immediately following completion of intensive PK.
Safety, tolerability, HIV RNA assessments were performed (Week 4
and every 4 weeks throughout). Target PK exposures were AUC(0-24)
range of 3767 mg*h/mL (primary) and C24 range 0.772.26 mg/ml
(secondary).
Results: Ten adolescents (7 female) with mean (SD) age 14 yrs (1.89)
and weight 57.3 kg (17.7) were enrolled. Nine subjects received DTG
50mg and 1 subject received DTG 35mg daily. Median Baseline (BL)
CD4 cell% and HIV-1 RNA log10 were 21.5% (IQR:18.426) and 4.40
log10 copies/mL (IQR:4.174.84), respectively. DTG demonstrated
moderate intersubject PK variability; geometric mean (CV%) AUC(0-24)
and C24 were 46.0 (43%) mg*h/ml and 0.90 (58%)mg/mL, respectively. HIV-1 RNA B40 c/mL was achieved (7/10 subjects (70%)) after
4 weeks of dosing; median change from BL was 2.8log10copies/mL
(95% CI: 3.1, 2.6). DTG was generally well tolerated, with one
Grade 3, no Grade 4 AEs, no discontinuations due to AEs, no trends
in lab abnormalities.
Conclusion: Preliminary data suggest DTG achieved target
mean AUC(0-24) and C24 in children ]12 to B18 years. DTG
plus OBT was generally well tolerated (Week 4). Data support further
DTG investigation at selected dose, and younger pediatric cohort
initiation.
B40 - Clinical trials and antiretroviral
therapy in children and adolescents
TUAB0202
Pharmacokinetics, safety and antiviral activity of
fosamprenavir/ritonavir-containing regimens in HIV-positive
four weeks to Btwo year-old children (48-week data, study
APV20002, a prospective, open-label, multi-centre, 48-week
cohort study)
M. Cotton1, H. Cassim2, N. Pavı́a-Ruz3, L. Ross4, S. Ford4, N. Givens5,
K. Cheng5 and J. Sievers5
1
Tygerberg Children’s Hospital, Tygerberg, South Africa. 2Perinatal
HIV Research Unit, Johannesburg, South Africa. 3Universidad
Nacional Autonoma de Mexico, Facultad de Medicina, Mexico, DF,
Mexico. 4GlaxoSmithKline, Research Triangle Park, United States.
5
GlaxoSmithKline, Uxbridge, United Kingdom
Presenting author email: jorg.x.sievers@gsk.com
Background: Pharmacokinetics, safety and antiviral activity of
fosamprenavir (FPV)/ritonavir (RTV) twice daily were evaluated
in protease inhibitor (PI)-naive and -experienced HIV-1-infected
children aged 6 months to B2 years (Cohort 1) and 4 weeks to B6
months (Cohort 2) primarily from South Africa and Mexico.
Methods: Intensive pharmacokinetic sampling was performed at
Week 2 or 8; pre-dose samples were collected every 412 weeks.
Safety and plasma HIV-1 RNA were monitored every 412 weeks.
Results: In total, 59 HIV-1-infected subjects received ]1 dose of
FPV/RTV; 54 were included in the intent-to-treat-exposed (ITT[E])
population: 28 in Cohort 1 and 26 in Cohort 2. Median exposure to
FPV was 640 days (range 81093), with 78% exposed 48 weeks. PK
parameters and comparisons with historical adult data are shown in
the table.
Sixty-four percent (18/28) in Cohort 1 and 58% (15/26) in Cohort 2
achieved Week 48 HIV-1 RNA B50 copies/mL (ITT[E], MSD F).
Overall, 9 subjects met virologic failure criteria. Median increase
in CD4cell percentages at Week 48 was 5% in both cohorts.
The most common adverse events (AEs) were diarrhoea, gastroenteritis, and upper respiratory tract infection. Drug-related grade
24 AEs occurred in 12/59 (20%) subjects; the most frequent
were blood cholesterol increased (5/59, 8%) and gastroenteritis
(2/59, 3%). Twenty-two subjects experienced serious AEs (SAEs); 3
events were considered drug-related. Three subjects died following
SAEs.
Conclusion: FPV/RTV dosing regimens achieved plasma APV exposures in Cohort 1 comparable to those from regimens approved in
adults; APV Ct was lower in Cohort 2 but clinical outcomes were
comparable. While the overall safety profile was similar to that
observed in older children and adults, more subjects reported
SAEs possibly reflecting the lower threshold for hospital admission
in this young population. The antiviral response was similar between
cohorts; the majority had undetectable HIV-1 RNA levels by
Week 48.
Historical healthy
adult
Plasma APV PK
parameter
700/100 mg BID1
N159
6 months to B2 years (Cohort 1)
45/7 mg/kg BID1
N10
6m to B2y vs. Historical
Adult2
4 weeks to B6 months (Cohort 2)
45/10 mg/kg BID1
N 9
4w to B6m vs. Historical
Adult2
0.720 (0.542, 0.957)
AUC(0t) (h.mg/mL)
37.0 (35.1, 38.9)
27.5 (14.5, 52.1)
0.744 (0.568, 0.975)
26.6 (15.2, 46.8)
Cmax (mg/mL)
5.62 (5.35, 5.92)
5.84 (3.35, 10.2)
1.04 (0.807, 1.34)
6.25 (3.82, 10.2)
1.11 (0.853, 1.45)
Ct (mg/mL)
2.17 (2.05, 2.30)
2.17 (1.69, 2.80)
1.00 (0.833, 1.21)
0.860 (0.500, 1.48)
0.397 (0.298, 0.528)
(n 158)
(n 29)
CL/F (mL/min/kg)
3.52 (3.33, 3.71)
22.8 (12.0, 43.1)
6.47 (4.67, 8.97)
22.9 (12.9, 40.6)
(n 11)
6.51 (4.62, 9.17)
(n 157)
1Geometric Mean (95% CI), 2Geometric least squares (GLS) Mean Ratio (90% CI).
65
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
TUAB0204
Safety and efficacy of etravirine in HIV-1-infected,
treatment-experienced children and adolescents: PIANO
48-week results
G. Tudor-Williams1, P. Cahn2, K. Chokephaibulkit3, J. Fourie4,
C. Karatzios5, S. Dincq6, T.N. Kakuda7, S. Nijs6, L. Tambuyzer6 and
F. Tomaka7
1
Imperial College Department of Medicine, London, United Kingdom.
2
Fundación Huesped, Buenos Aires, Argentina. 3Mahidol University,
Bangkok, Thailand. 4Dr Jan Fourie Medical Practice, Dundee, South
Africa. 5McGill University Health Centre, Montréal, Canada. 6Janssen
Infectious Diseases BVBA, Beerse, Belgium. 7Janssen Research &
DevelopmentLLC, Titusville, United States
Background: Etravirine has demonstrated efficacy and safety in
treatment-experienced, HIV-1-infected adults. Pediatric development
is ongoing.
Methods: PIANO (TMC125-C213; NCT00665847) is a 48-week, Phase
II, open-label trial of the safety, efficacy and pharmacokinetics of
etravirine 5.2 mg/kg (maximum dose 200mg) bid in HIV-1-infected,
treatment-experienced children (6 B12 years) and adolescents
(12 B18 years) with screening viral load (VL) ]500 copies/mL.
All patients received an investigator-selected, optimized background
regimen (OBR) of a ritonavir-boosted PI plus N(t)RTIs and optional
enfuvirtide and/or raltegravir. Week 48 (W48) data are reported.
Baseline characteristics
Viral load median log10 copies/mL (range)
CD4 count, median cells/mm3 (range)
Previous NNRTI use, n(%)
0
1
2
W48 safety, n (%)
Any AE
Any serious AE
Any grade 3/4 AE*
Most common AEs (regardless of severity or causality)$
Upper respirator/ tract infection
Any rashz
Diarrhea
Vomiting
Cough’
Most common AEs at least possibly related to etravirine’
Any rashz
Diarrhea
Any ] grade 2 AE at least possibly related to etravirine
W48 efficacy
VL B50 HIV-1 RNA copies/mL, (NC F), n (%)
VL B50 HIV-1 RNA copies/mL(TLOVR), n (%)
Mean (SE) change from baseline in CD4 cell count,
cell/mm3.
Results: Overall, 101 patients were enrolled (63% female, 49% white)
and 76 (75%) completed the trial; most discontinuations were for
adverse events (AEs) or trial non-compliance (8% each). At W48, 65%
of patients were adherent by PENTA adherence questionnaire. By pill
count, 39% (children 46%, adolescents 35%) were 95% adherent;
70% were 80% adherent. The most common drug-related AE was
rash (18%) (Table). Four percent discontinued due to rash. Serious
AEs were seen in 5% of patients while 14% experienced a grade 3/4
AE. Laboratory toxicities were predominantly grade 1/2. At W48,
56% of patients achieved VL B50 copies/mL (intent-to-treat, noncompleterfailure), with better responses in children than adolescents (Table). Median time to first response (VL B50 copies/mL) was
16 weeks (children) and 24 weeks (adolescents). Forty one patients
(41%) were classed as virologic failures (VF): 29 non-responders and
12 rebounders. Of 30 VFs with available genotype at endpoint, 18
(60%) developed NNRTI resistance-associated mutations, most
commonly: Y181C (n 8), E138A (n 3), L100I (n 3) and/or V90I
(n 3).
Conclusion: The efficacy, safety and resistance profiles of
etravirine 5.2 mg/kg bid plus OBR in this difficult-to-treat, antiretroviral-experienced pediatric population were comparable to
those observed in treatment-experienced adults (DUET trials).
Responses were better in children than adolescents, most likely
due to less advanced disease, better adherence and less previous
NNRTI use.
Children ( ]6 B 12
Adolescents (]12 Bl8
All patients
years) N 41
years) N 60
N 101
36 (27)
443 (391441)
4.0 (26)
356 (71345)
39 (27)
385 (71441)
14 (34)
25 (81)
2 (5)
11 (18)
42 (70)
7 (12)
25 (25)
67 (66)
9 (9)
34 (83)
0
6 (15)
55 (92)
5 (8)
8 (13)
89 (88)
5 (5)
14 (14)
10 (24)
6 (15)
5 (12)
4 (10)
5 (12)
17 (28)
17 (28)
11 (18)
7 (12)
8 (13)
27
23
16
11
13
4 (10)
1 (2)
6 (15)
14 (23)
6 (10)
15 (25)
18 (18)
7 (7)
21 (21)
28 (68)
28 (68)
178 (40)
29 (48)
26 (43)
141 (27)
57 (56)
54 (53)
156 (23)
(27)
(23)
(16)
(11)
(13)
*Two children reported grade 4 thrombocytopenia and three patients had a grade 3 AE considered at least possibly related to etravirine (two
children one with rash maculo-papular one with hypersensitivity, one adolescent with diarrhea): $occuring in 10% of patients overall;
z
grouped term including rash not further specified, rash macula-papular, rash generalized, rash erythematous, rash macular rash papular and
rash puritic; ’occurnng in 5% of patients overall; AE, adverse event NC F, non-completer equals failure; SE standard error; TLOVR, time-toloss of virologic response algorithm.
66
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
TUAB0205
Background: New antiretrovirals are needed for HIV children.
IMPAACT P1066 is a Phase I/II open label multicenter trial to
evaluate pharmacokinetics (PK), safety, tolerability, and efficacy of
multiple RAL formulations in treatment experienced HIV youth.
RAL was given with an optimized background regimen. Dose
selection was based upon intensive PK and safety data: 400 mg
BID of RAL film-coated tablet (618 years) and weight-based dosing
( 6mg/kg BID) of RAL chewable tablet (2 to B12 years). Here we
present safety and efficacy results at 24 and 48 weeks in the 96
subjects who received the selected RAL dose.
Methods: Subjects were stratified sequentially in 3 age cohorts (I,
1218 years; II, 6 B 12 years; III, 2 B 6 years); Cohort I enrolled
first. Safety data through Week 48 was assessed. Grade 3 or
serious adverse events (AE) were summarized. Primary virologic
endpoint was vRNA B400c/mL or ]1 log reduction. Secondary
endpoints were vRNA B50c/mL, and change in CD4 count (%).
Efficacy analyses used Observed Failure missing data approach.
Results: Baseline characteristics, virologic and immunologic responses at weeks 24 and 48 for 96 subjects are in tables. Overall,
IMPAACT P1066: raltegravir (RAL) safety and efficacy in
HIV infected () youth two to 18 years of age through
week 48
S. Nachman1, E. Acosta2, N. Zheng3, H. Teppler4, B. Homony4, X. Xu4,
C. Alvero3, E. Handelsman5, C. Worrell6, B. Graham7, M. Toye8,
E. Petzold9, A. Wiznia10 and and the P1066 Group
1
SUNY Stony Brook, Pediatrics, Stony Brook, United States.
2
University of Alabama at Birmingham, Birmingham, United States.
3
Harvard School of Public Health, Boston, United States. 4Merck,
North Wales, United States. 5Division of AIDSNIAID, NIH
Bethesda, United States. 6Natl Inst of Child Hlth and Human Devt,
Bethesda, United States. 7Frontier Science Inc, Buffalo
United States. 8Baystate Medical Center, Springfield, United States.
9
Social and Scientific Systems, Durham, United States. 10Jacobi
Medical Center, Albert Einstein College of Medicine, Bronx
United States
Presenting author email: sharon.nachman@stonybrook.edu
Cohort I 12 18 years,
N 59 Film coated
Cohort IIA 6 B12
years, N 4 Film
Cohort IIB 6 B12
years, N 13
Cohort III, 2 B6
years, N 20
Total, 2 18 years,
tab
coated tab
Chewable tab
Chewable tab
N 96
Age (years), median [range]
15 [1218]
10.5 [811]
Male gender
50%
75%
53.8%
35%
49%
Caucasian, Black
35.6%, 59.3%
25%, 75%
46.2%, 53.8%
25%, 60%
34.4%, 59.4%
Plasma HIV-1 RNA (log10
4.3 [3.16]
4.4 [3.54.9]
9 [611]
4.3 [3.55.2]
3 [25]
13 [218]
4.3 [2.75.3]
4.3 [2.76]
copies.mL), mean [range]
CD4 cell count (cells/mm3),
396.5 [0872]
806.5 [2741515]
529 [161000]
median [range]
CD4%, median [range]
1086.5 [3232361]
481 [02361]
20% [044]
28% [1331.7]
33% [240]
28.7% [12.941.8]
23.3% [044]
CDC HIV category B or C
76.3%
25%
23.1%
40%
59.4%
Prior NNRTI
86.4%
75%
84.6%
50%
78.1%
Prior PI
96.6%
75%
61.5%
60%
83.3%
Baseline Patient Characteristics.
Cohort I 12 18 yrs
Cohort IIA 6 B12
Cohort IIB 6 B12
Cohort III 2 B6
Total 2 18 yr
N 59
yrs N4
yrs N13
yrs N20
N 96
WEEK 24 RESPONSE
Completed Treatment as of
94.9%
100%
72.4%
50%
100%
100%
94.9%
70%
71.6%
D#127
Achieved ]1 log10 HIV RNA
decline or B400 c/mL
Mean CD4 change from
114.4 (4.1%)
35.8 (2.2%)
76.9%
143.4 (0.8%)
147.2 (5.3%)
119.0 (3.8%)
baseline cells/mm3 (%)
WEEK 48 RESPONSE
Completed Treatment as of
93.2%
100%
92.3%
75%
90.9%
100%
94.8%
D#295
Achieved ]1 log10 HIV RNA
75%
84.2%
78.9%
decline or B400 c/mL
Achieved HIV RNA B50 c/mL
Mean CD4 change from
57.1%
168.2 (5.2%)
50%
189.5 (6.0%)
54.5%
76.8 (1.6%)
57.9%
158.1 (4.3%)
56.7%
155.7 (4.6%)
baseline cells/mm3 (%)
Efficacy Outcomes from IMPAACT P1066.
67
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
virologic response was observed in 78.9%, RNA B50c/mL in
56.7%, with mean CD4 increase 155.7 cells/uL. Through Week 48,
there were 15 subjects with Grade 3 clinical AEs (1 subject
with drug related [DR] psychomotor hyperactivity, abnormal behavior and insomnia); 16 subjects with Grade 3 laboratory AEs
(1 with DR AST and ALT); 15 subjects with serious clinical AEs (1 with
DR rash); 2 subjects with serious laboratory AEs (1 with DR
transaminase increased); no discontinuations due to AEs and no
deaths.
Conclusion: Two RAL formulations were studied in HIV infected
youth ages 2 to 18 years. At the selected doses, both formulations
were well-tolerated and showed favorable virologic and immunologic
responses.
B41 - Adherence in children and
adolescents
THAE0101
Success in reaching national pediatric uptake targets and
similar adult retention rates in pediatric HIV clinics in the
rural Southern Rift Valley (SRV) province of Kenya
A. Miruka1, R. Achieng1, A. Aoko1, J. Tarus1, C. Sigei1, P. Yegon1,
J. Maswai1, F. Sawe1, D. Shaffer2,3 and K. Crawford3
1
Kenya Medical Research Institute/Walter Reed Project, Kericho,
Kenya. 2US Army Medical Research Unit, Kenya (USAMRU-K),
Kericho, Kenya. 3US Military HIV Research Program (USMHRP),
Bethesda, United States
Presenting author email: amiruka@wrp-kch.org
Background: In Kenya, an estimated 7,000-10,000 children are HIV
infected yearly. National targets for 10% of all HIV clinic patients
registered being pediatric are often difficult to reach or fall behind
adult uptake. In addition, concerns exist regarding retention of
children in HIV/AIDS clinics. Such challenges are often magnified in
rural settings due to frequent changes in caregivers,distances away
from pediatric clinics, and extremes in poverty.
Pediatric HIV clinic Uptake.
Track B Clinical Science
Methods: In 2004, HIV/AIDS care and treatment programs began
developing under the President’s Emergency Plan for AIDS Relief
(PEPFAR) program in the SRV Province of Kenya, a largely rural
population. Effort has been made to decentralize care, making more
clinics closer to rural populations available. In addition, initiatives
such as the ‘‘Mwangalizi’’ (‘‘care givers’’, often HIV positive adults
linked with children to assure they come to HIV clinics) project have
been implemented, and pediatric HIV support groups have been
established. We describe aggregate program level data for the
development of/uptake in HIV pediatric clinics.
Results: Between 2004 and 2011, 17,572 children received HIV
testing through both voluntary counseling and testing (VCT) and
diagnostic testing and counseling (DTC) initiatives. 5,310 children
(mean age 10.0 / 3.3 years, 50.6% female) were enrolled in 57
pediatric HIV clinics. Of those enrolled, 44.3% started first line ART,
2.5% switched to 2nd line ART, and 1 has advanced to 3rd line ART. In
2005, 7.0% of HIV clinic attendees were children on ART, which
increased to 10.5% in 2011 (p B0.001). In 2011, the retention rate
for adults who had started ART was 82.2%. In comparison, the
retention rate for pediatric patients who had started ART was nearly
the same, 81.1% (p 0.2).
Conclusion: National pediatric HIV clinic enrollment goals can be met
in rural Kenya with ART retention nearly the same as retention in
adults.
B42 - Complications of HIV therapy in
children and adolescents
MOAB0201
Lipid profile in children randomized to immediate versus
deferred nevirapine-based antiretroviral therapy in the
PREDICT study
S. Kanjanavanit1, T. Puthanakit2,3, P. Kosalaraksa4,
R. Hansudewechakul5, C. Ngampiyaskul6, S. Pinyakorn2,
W. Luesomboon7, S. Vonthanak8, J. Ananworanich2,9,10,
K. Ruxrungtham2,10 and PREDICT study group
1
Nakornping Hospital, Chiang Mai, Thailand. 2HIV Netherlands
Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross
AIDS Research Center, Bangkok, Thailand. 3Department of Pediatrics,
Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
4
Department of Pediatrics, Faculty of Medicine, Khon Kaen
University, Khon Kaen, Thailand. 5Chiangrai Prachanukroh Hospital,
Chiangrai, Thailand. 6Prapokklao Hospital, Chantaburi, Thailand.
7
Queen Savang Vadhana Memorial Hospital, Chonburi, Thailand.
8
National Center for HIV/AIDS, Dermatology and STDs, Phnom Penh,
Cambodia. 9SEARCH, Thai Red Cross AIDS Research Center, Bangkok,
Thailand. 10Department of Medicine, Faculty of Medicine,
Chulalongkorn University, Bangkok, Thailand
Presenting author email: skanjanavanit@gmail.com
Background: Lipid abnormality is a common long-term complication
in HIV-infected children. This study aimed to compare lipid profiles in
children randomized to immediate versus deferred nevirapine-based
antiretroviral therapy (ART).
Methods: This was a substudy of PREDICT (NCT00234091), a 144week randomized trial of immediate ART (at CD4 1524%) versus
deferred ART (at CD4B15%) in ART-naı̈ve Thai and Cambodian
children 112 years of age with baseline CD4 between 1524%.
Fasting lipid profile was compared between arms. Statistical analysis
was done using Paired t-test or Wilcoxon singed-rank test where
68
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
Table 1. Growth, CD4, HIV RNA, lipids at weeks 0 and 144
Week 0
Week 144
Parameters
Immediate (n 129)
Deferred (n134)
Immediate (n 94)
Deferred (n127)
Weight for age Z-score
1.3 ( 2.0. 0.7)
1.3 (2.1. 0.8)
1.3 ( 1.7. 0.4)
1.4 (2 0. 0 9)
Height for age Z-score
1.6 ( 2.5. 0.7)
1.7 (2.5. 0.9)
1.5 ( 2.2.0 6)
1.7 (2.5. 0.9)
CD4%
19 (1622)
20 (1724)
34 (2939)
24 (1930)*
CD4 cell count, cells/mm3
611 (420829)
619 (479847)
977 (7411274)
662 (505928)*
HIV RNA, log 10 copies/mL
4.9 (4.35)
4.7 (4.35)
1.7 (1.61.7)
3.4 (1.64.7)*
Dyslipidemia# of any kind, n (%)
76 (59)
90 (67)
35 (37)
78 (61)*
Total cholesterol, mg/dL
140 (119156)
136 (121158)
166 (149. 190)
147 (132171)*
Triglyceride, mg/dL
LDL, mg/dL
98 (69131)
76 (69131)
104 (7913S)
74 (79138)
91 (69. 113)
91 (78. 107)
101 (73132)*
88 (73104)
HDL, mg/dL
42 (3349)
42 (3450)
55 (4867)
43 (3452)*
TC/HDL ratio
3.3 (2.74.0)
3.3 (2.84.2)
2.8 (2.53.6)
3.5 (2.94.2)*
*p valueB0.05 between immediate and deferred arm, t-test or wilcoxon rank-sum test.
Dylipidemia defined as Total cholesterol 200 mg/dl, Triglyceride 130 mg/dl, LDL130 mg/dl, HDL 540 mg/dl.
#
appropriate. Random effects model was used for multivariate
analysis.
Results: Data from 129 immediate arm and 134 deferred arm
children were included. The median (IQR) age was 6.5 (4.18.5)
years, 42% were male and 57% were Thai. Median fasting time was
8 hours. Parameters did not differ significantly between arms at
week 0 (Table 1). By week 144, 60 deferred arm children had started
ART. Dyslipidemia was significantly less common in the immediate
arm. The immediate arm had significantly higher total cholesterol
(TC), low-density lipoprotein (LDL), and high density lipoprotein
(HDL) but lower triglyceride and TC/HDL ratio than the deferred arm.
By multivariate analysis, the mean differences over 144 weeks
between the immediate arm versus the deferred arm without ART
(n 73) were significant for all lipid parameters: TC (20.2, pB0.001),
triglyceride (9.8, p0.006), LDL (9.1, pB0.001) and HDL (13.0,
pB0.001) whereas only HDL was significantly different when the
immediate arm were compared to the deferred arm children with
ART (n 61) (4.9, p 0.001).
Conclusion: After 3 years, children randomized to immediate
nevirapine-based ART had less dyslipidemia and lower TC/HDL ratio
than the deferred ART group. This supports earlier nevirapine-based
initiation to achieve favorable lipid profile in children with mild to
moderate HIV-associated immune deficiency.
MOAB0203
Mitochondrial function and metabolic abnormalities in
children with perinatally-aquired HIV infection in the
Pediatric HIV/AIDS Cohort Study (PHACS)
T.L. Miller1, J. Wang2, D.L. Jacobson2, J.K. Takemoto3, T. Sharma4,
M.E. Geffner5, D.E. Libutti3, S. Siminski6, L. Dooley6, G. Somarriba1,
P. Graham1 and M. Gerschenson7
1
University of Miami, Pediatrics, Miami, United States. 2Harvard
School of Public Health, Boston, United States. 3University of Hawaii
Manoa, Honolulu, United States. 4Children’s Hospital Boston, Boston,
United States. 5Children’s Hospital Los Angeles, Los Angeles, United
States. 6Frontier Science & Technology Research Foundation, Inc.,
Amherst, United States. 7Cellular and Molecular Biology, University
of Hawaii Manoa, Honolulu, United States
Presenting author email: gerschen@hawaii.edu
Background: Metabolic abnormalities, common among perinatally
HIV-infected children (HIV), may be caused by mitochondrial
dysfunction that is induced by antiretroviral therapy (ARV) or
chronic viral infection. We compared mitochondrial function [oxidative phosphorylation (OXPHOS) enzyme activities and lactate
levels] of HIV and HIV-exposed, uninfected (HEU) children and,
among HIV, determined associations with fasting glucose,
insulin, and homeostatic model assessment of insulin-resistance
(HOMA-IR).
Methods: HIV and HEU were enrolled from the PHACS Adolescent
Master Protocol. Children with known, non-HIV-associated mitochondrial disorders were excluded. Demographic and BMI [all] and
CD4, HIV viral load, ARV exposures, and fasting insulin/glucose
[HIV only] were collected. Main outcomes included venous and
point-of-care (POC) lactate, venous pyruvate, and PBMC NADH
dehydrogenase (CI) and cytochrome c oxidase (CIV) enzyme
activities. A Wilcoxon test was used to compare outcomes between
HIV and HEU; Spearman correlations were determined between
insulin/glucose and OXPHOS activity in HIV.
Results: 112 HIV and 66 HEU children were enrolled as of
December 2011. HIV were older than HEU (15.8yr vs 12.4yr)
with similar gender and racial distributions. BMI-Z was lower in
HIV (0.41SD vs 0.54SD). Among HIV, 45% were CDC stage B/C
and 74% had CD4 500 cell/mm3 with 60% having viral
load B400cp/mL. 56% were on HAART, PI-based ARVs. Median
glucose was 87mg/dL (range 74110), insulin was 13.6IU (range
4.783) and HOMA-IR was 3.1 (range 120.7). POC lactate was
higher and venous pyruvate lower among HIV vs HEU (Table),
while C1 and CIV activities did not differ between groups. Among
HIV with measures available, we observed a negative correlation
of fasting glucose with CI OXPHOS activity (n 26; r 0.38;
p0.06) and a positive correlation with venous lactate (n 34;
r0.31; p 0.07).
Conclusion: Preliminary analyses show higher POC lactate in
HIV compared to HEU children and that mitochondrial dys-
69
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
function may be associated with metabolic abnormalities in HIV
children.
Comparison of Mitochondrial Measures by HIV
Median (IQR)
N
HIV
N
HEU
POC lactate
(mmol/L)
Venous lactate
(mmol/L)
Venous pyruvate
(mmol/L)
CI OXPHOS
enzyme activity
(OD/min/ug e-6)
CIV OXPHOS
enzyme activity
(OD/min/ug e-6)
96 1.6
(1.2, 1.9)
89 1.0
(0.79, 1.43)
87 0.08
(0.05, 0.11)
45 17.6
(11.0, 26.7)
58 1.3
(1.0, 1.8)
59 1.4
(1.0, 1.87)
56 0.10
(0.07, 0.13)
35 18.2
(13.5, 26.6)
45 23.7
(21.5, 29.7)
35 25.5
(19.2, 29.1)
P-value
0.06
0.001
0.03
0.35
0.75
MOAB0205
Clinical screening shows high prevalence of peripheral
neuropathy in children taking antiretroviral therapy in rural
South Africa
M. van Ramshorst1, H. Struthers2, J.A. McIntyre2,3 and R.P.H. Peters1
1
Anova Health Institute, Khutso Kurhula Project, Tzaneen
South Africa. 2Anova Health Institute, Johannesburg, South Africa.
3
University of Cape Town, School of Public Health, Cape Town
South Africa
Presenting author email: petersr@anovahealth.co.za
Background: Peripheral neuropathy is a well-recognised and common condition in HIV-infected adults and may be related to use of
antiretroviral therapy (ART) as well as be directly caused by HIV
infection. Data on the prevalence, manifestations and risk factors of
neuropathy in children are limited. Only few tools are available for
clinical screening for peripheral neuropathy in children. We used the
neuropathy symptom score (NSS) and neuropathy disability score
(NDS) to screen for peripheral neuropathy in a cohort of children on
ART.
Methods: In this cross-sectional study we included 182 children aged
5-15 years attending to healthcare facilities for ART collection in rural
Mopani District, South Africa. Subjective and objective assessment of
neuropathy was done using the NSS respectively NDS. These scores
are feasible for resource-poor and skills-limited settings and only
require a reflex hammer, cotton butt, tooth pick, and cold water.
A definite diagnosis of peripheral neuropathy was defined by NSS ]3
or NDS ] 2.
Results: Neuropathy screening was completed for 174/182 (96%) of
children as 8 children did not fully cooperate. Median age was 9
years old and time on ART 2.0 years (2 months-6.4 years) with 86%
on a stavudine-containing regimen. Symptoms related to neuropathy
were reported by 49 children (27%) while NDS was positive for 25
children (14%). Forty-one (24%) of children fulfilled the criteria of
peripheral neuropathy. Co-trimoxazole use was negatively associated
with neuropathy presentation (OR 0.42, 95% CI 0.200.88;
p0.019) while there were tendencies for peripheral neuropathy
to be associated with older age (p 0.09) and longer time on ART
(p 0.06).
Conclusion: Peripheral neuropathy is a common condition in children
collecting ART at healthcare facilities in rural Mopani District. The
NSS and NDS can be used to screen for this condition in resourcepoor settings.
TUPDB0103
Development of the first liquid chromatography-tandem
mass spectrometry assay for antiretrovirals in meconium
S. Himes1, K. Scheidweiler1, K. Tassiopoulos2, D. Kacanek3, R. Hazra4,
K. Rich5, M. Huestis1 and for the Pediatric HIV/AIDS Cohort Study
(PHAC)
1
National Institute on Drug Abuse (NIDA), Chemistry and Drug
Metabolism, Baltimore, United States. 2Harvard School of Public
Health, Epidemiology Department, Boston, United States. 3Harvard
School of Public Health, Center for Biostatistics in AIDS Research,
Boston, United States. 4National Institute of Child Health and Human
Development, Pediatric Adolescent and Maternal AIDS Branch,
Bethesda, United States. 5University of Illinois at Chicago, Pediatrics
Department, Chicago, United States
Presenting author email: sarah.himes@nih.gov
Background: Antiretroviral (ARV) administration to HIV positive
pregnant women and neonates reduces perinatal HIV transmission
to less than 2% worldwide. However, concerns have been raised
about potential toxicity in some neonates following gestational ARV
exposure. Precise quantification of ARV exposure by history is
difficult. Quantitative meconium analysis may better reflect fetal
exposure during the third and perhaps second trimesters than
history alone. Therefore, we developed and validated the first liquid
chromatography-tandem mass spectrometry (LC-MS/MS) assay for
ARVs and metabolites in meconium.
Methods: Blank meconium (0.25g) was fortified with 16 ARVs and 4
metabolites, chosen based on prevalence of use by HIV-infected
mothers in the SMARTT (Surveillance Monitoring of ART Toxicities)
Study of PHACS. Samples were homogenized in methanol and
subjected to solid phase extraction prior to quantification by LCMS/MS. Tenofovir (TDF), lamivudine (3TC), emtricitabine (FTC),
abacavir (ABC) and its carboxylate (CABC) and glucuronide (GABC)
metabolites, nevirapine (NVP), raltegravir (RAL), saquinavir (SQV),
amprenavir (AMP), darunavir (DRV), atazanavir (ATV), ritonavir (RTV),
lopinavir (LPV), nelfinavir (NFV) and its bioactive hydroxyl (M8)
metabolite were quantified with positive ionization; stavudine (d4T),
efavirenz (EFV), zidovudine (AZT) and its glucuronide (GAZT)
metabolite were quantified with negative ionization.
Results: Chromatographic separation was achieved with gradient
elution; two injections were required due to the need for both
positive (35 min) and negative (18 min) ionization modes. Extraction
efficiencies were greater than 60% for all analytes except GABC
(30%), and TDF, 3TC, GAZT and CABC (50%). Linear calibration curves
employing 1/x2 weighting ranged from 102500ng/g (TDF, FTC, ABC,
GABC, NVP, RAL, SQV, ATV, RTV, LPV, NFV, and M8), 502500ng/g
(3TC), 752500ng/g (CABC), 10025,000ng/g (AMP, DRV, AZT, EFV)
and 50025,000ng/g (d4T, and GAZT).
Conclusion: We developed a selective and sensitive LC-MS/MS
method to detect antiretroviral medications and metabolites in
meconium, which may be useful in quantifying the in utero ARV
exposure for children of HIV-infected women.
B45 - Cardiovascular disease
THAB0202
Increased platelet activity and immune activation in HIVpositive subjects on antiretroviral therapy is attenuated
with low-dose aspirin
M. O’Brien1, M.A. Nardi2, E. Montenont2, V. Valdes2, L. Hu2,
M. Merolla2, G. Gettenberg2, J. Aberg2, N. Bhardwaj2 and J.S. Berger2
70
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
1
New York University Medical School, Medicine, Infectious Diseases,
New York, United States. 2New York University Medical School, New
York, United States
Background: Mechanisms for increased cardiovascular risk in
HIV-infected adults are incompletely understood, but heighted
inflammation leading to a pro-thrombotic state has been proposed
as a major contributor. In vitro platelet aggregation has been studied
as a robust biological marker of coronary events and mortality.
Methods: We studied platelet aggregation in 25 HIV-infected
subjects on ART with undetectable plasma HIV-1 RNA, median CD4
537 cells/mm3 (73.9%men) and 29 healthy HIV seronegative controls
(44.4%men) in response to submaximal adenosine diphosphate (ADP,
0.4uM), arachidonic acid (AA, 0.15mM), or without agonist (spontaneous platelet aggregation [SPA]). The effects of one week of aspirin
81mg daily on activation markers, as measured by flow cytometry,
and platelet aggregation were investigated. Two-tailed paired t tests
and non-parametric Mann-Whitney U test tests were used for
statistical analyses, with results given as medians with interquatile
ranges.
Results: Compared to controls, HIV subjects on ART had increased
platelet aggregation in response to ADP (10.8% [6.5, 42.3] vs 7.6%
[3.3, 10.2], p0.02), AA (54.9% [8.7, 89.9] vs 11% [2.5, 77.6],
pB0.05), and without agonist (SPA) 7.5% [4.7, 11.4] vs 5% [2.9,
9.1], pB0.05). Following aspirin therapy, percent aggregation in
response to ADP and AA decreased significantly (p B 0.01 for each
comparison). Compared to controls, HIV subjects on ART had
increased %HLADRCD38CD4 Tcells(8.3%[4.1, 12.1] vs
3.9%[1.4, 6.1], p 0.01) and %HLADRCD38 CD8 Tcells
(0.46%[0.21, 0.58] vs 0.21%[0.18, 0.34], p 0.01). Following aspirin
therapy there was a significant decrease in % HLADRCD38
CD4 Tcells, pB0.01 and a trend in decreased % HLADRCD38
CD8 Tcells, p 0.08, in HIV subjects but no significant change was
noted in controls.
Conclusion: Platelet activity is increased in HIV-infected subjects on
suppressive ART, which may contribute to their heightened cardio-
vascular risk. One week of 81mg of aspirin attenuated platelet
activation and immune activation in HIV-infected subjects on
suppressive ART.
B48 - Endocrine and metabolic issues
(e.g., diabetes, hyperlipidemia)
THAB0201
The interplay of the osteoprotegerin/RANKL axis and
dysfunctional HDL in HIV-positive adults: ACTG NWCS 332/
A5078 study
T. Kelesidis1, M. Kendall2, O. Yang1 and J. Currier1
1
David Geffen School of Medicine at UCLA, Los Angeles, United
States. 2Harvard School of Public Health, Boston, United States
Background: Limited data exist regarding the relationship between
dysfunctional HDL (dys-HDL) and the osteoprotegerin (OPG)/receptor activator of the NF-kB ligand (RANKL) in HIV infection. Oxidized
HDL (dys-HDL) has been shown to activate the NF-kB pathway in
vitro. In view of this observation and the important role of
biomarkers of activation of the NF-kB pathway (RANKL/OPG axis)
in systemic inflammatory conditions, we used a novel assay that
measures oxidation of HDL to explore possible associations between
dys-HDL with RANKL/OPG and parameters that may predict these
biomarkers.
Methods: We used cryopreserved serum samples from a prospective
study (A5078) where subjects were enrolled as risk factor-matched
triads of HIV-infected subjects (n55) and HIV-uninfected individuals (n 36). Relationships between HIV infection, RANKL, OPG,
RANKL/OPG, and dys-HDL were assessed using Wilcoxon tests and
mixed effects linear regression analysis. The baseline covariates
Total (N 91)
Characteristic
Gender
Age (years)
Male
Median (IQR)
Race/Ethnicity
HIV RNA copies/ml)
B50
84 (92%)
41 (3645)
HIV (N 55)
Not HIV (N 36)
P value
52 (95%)
41 (3745)
32 (89%)
40 (3645)
0.428
0.589
White Non-Hispanic 69 (76%)
42 (76%)
27 (75%)
0.722
46 (84%)
46 (84%)
23.9 (19.3, 27.0)
0.62
Baseline CD4 T cells (cells/mm3) Median (IQR)
488 (354692)
488 (354692)
DOR ( 104 FU/min)
Median (IQR)
24.1 (19.8, 27.6)
24.6 (20.2, 28.1)
RANKL (pg/ml)
Median (IQR)
22,124 (10,352, 44,003) 15,059 (7,764, 26,537) 42,829 (17,249, 70,496) B0.001
OPG (pg/ml)
Median (IQR)
1,054 (781, 1,535)
1,087 (781, 1,601)
1,013 (772,1,289)
RANKL/OPG
Median (IQR)
18.23 (9.98, 48.81)
13.32 (6.72, 27.80)
37.68 (18.16,75.54)
0.52
B0.001
Baseline subject variables by group.
Univariate models
Covariate
Parameter Estimate (95% CI)
Multivariate models
P value
Parameter Estimate (95% CI)
P value
Baseline DOR (per 10,000 FU/min)
Waist-to-hip ratio (per 0.1 units)
3.97 ( 6.94, 0.99)
0.012
3.75 (6.57, 0.92)
0.013
Baseline RANKL (per 1000 pg/ml)
0.07 (0.01, 0.13)
0.020
()
()
0.06 ( 0.33, 0.21)
0.644
()
0.87 (0.22, 1.53)
0.012
Baseline OPG (per 100 pg/ml)
Baseline RANKL/OPG (per 10 units)
0.81 (0.16, 1.47)
()
0.019
Predictors of oxidative properties of HDL.
71
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
considered in the analysis are shown in Table 1 and also included
fasting glucose and lipids, insulin, use of statins, anthropometric
parameters of obesity, years of protease inhibitors (PI) use, and nadir
CD4 T cells. Significant (p B0.05) variables were considered in
multivariate models. RANKL and OPG were assessed by ELISA and
dys-HDL by a fluorometric assay based on the oxidation rate of
dihydrorhodamine (DOR) which reflects the oxidative (functional)
properties of HDL (J Lipid Res 2011;52:234151).
Results: Baseline measurements of 91 subjects appear in Table 1.
HIV infection was associated with significantly lower baseline
levels of RANKL and RANKL/OPG (Table 1). Within the HIV-infected
subjects, baseline RANKL/OPG was significantly associated with
baseline DOR (p 0.02, Table 2).
Conclusion: RANKL/OPG axis may be regulated differently in HIVinfected compared to -uninfected adults and is independently
associated with changes in functional properties of HDL in HIVinfected subjects. These data are consistent with previous in vitro
results that have shown that oxidized HDL may affect the NF-kB
pathway.
B51 - Immune activation and
inflammatory state
THLBB06
Associations of inflammatory markers with AIDS and non-AIDS
clinical events after initiation of antiretroviral therapy (ART):
AIDS Clinical Trials Group A5224s, a substudy of ACTG A5202
G.A. McComsey1, D. Kitch2, P.E. Sax3, C. Tierney2, N.C. Jahed4,
K. Melbourne5, B. Ha6, T.T. Brown7, A. Bloom8, N. Fedarko7, E.S. Daar9
and Adult Aids Clinical Trials Group A5224s
1
Case Western Reserve University, Cleveland, United States. 2Harvard
School of Public Health, Boston, United States. 3Brigham and
Women’s Hospital and Harvard Medical School, Boston,
Table 1.
United States. 4Social & Scientific Systems, Inc, Silver Spring,
United States. 5Gilead Sciences, Foster City, United States.
6
GlaxoSmithKline, Research Triangle, United States. 7Johns Hopkins,
Baltimore, United States. 8Frontier Science and Technology Research
Foundation, Inc., Amherst, United States. 9Los Angeles Biomedical
Research Institute at Harbor-UCLA Medical Center, Torrance,
United States
Presenting author email: gam9@case.edu
Background: The association of inflammatory biomarkers with
clinical events after ART initiation is unclear.
Methods: A5202 randomized 1857 treatment-naive subjects
to abacavir/lamivudine or tenofovir DF/emtricitabine with efavirenz
or atazanavir/ritonavir. Substudy A5224s measured inflammatory
biomarkers on all substudy subjects with available plasma from
baseline and weeks 24 or 96. The association of hsCRP, IL-6, sTNF-RI,
sTNF-RII, TNF-a, sVCAM-1, and sICAM-1 with times to AIDS and nonAIDS defining events was analyzed with Cox proportional hazards
models, with adjustment by ART assignment, and HIV-1 RNA or CD4.
Time-updated analyses used the most current value.
Results: Analysis included 244 subjects; 85% male, 48% white
non-Hispanic, with median age 39 years, HIV-1 RNA 4.6 log10
copies/mL, and CD4 240 cells/mL. A total of 13 AIDS-defining events
(9 opportunistic infections; 3 AIDS-cancers, 1 recurrent bacterial
pneumonia) and 18 non-AIDS defining events (6 diabetes, 4 cancers,
3 cardiovascular, 5 pneumonias) occurred. Higher baseline IL-6,
sTNF-RI, sTNF-RII, and sICAM-1 were significantly associated with
increased risk of AIDS-defining events. Adjustment for baseline HIV-1
RNA did not change results, while adjusting for CD4 count left sTNFRI and sICAM-1 significantly associated with increased AIDS-defining
events risk. Time-updated values of these biomarkers were also
associated with increased risk of AIDS-defining events, even after
adjusting for ART assignment, baseline and changes in CD4 and HIV-1
RNA. For non-AIDS events, only baseline hsCRP was significantly
associated with increased risk; after adjustment for baseline CD4
count, IL-6 became significantly associated with higher risk. Analyses
of time-updated biomarker value showed TNF-a to be significantly
Baseline and Time-Updated Biomarker Association with AIDS-Defining Events
Unadjusted
Biomarker
HR (95% CI)
p-value
Baseline CD4, NRTI and
Time-Updated CD4, NRTI
NNRTI/PI Adjusted
and NNRTI/PI Adjusted
HR (95% CI)
p-value
HR (95% CI)
p-value
1.18 (0.78, 1.76)
0.43
1.92 (1.04, 3.55)
0.037
Baseline hsCRP (per 1 log, ug/ml higher)
1.21 (0.80, 1.83)
0.36
1.26 (0.84, 1.88)
0.26
Time-updated hsCRP (per 1 log, ug/ml higher)
1.17 (0.78, 1.77)
0.44
1.17 (0.78, 1.75)
0.44
Baseline IL-6 (per l log, pg/ml higher)
1.98 (1.06, 3.69)
0.032
1.79 (0.96, 3.34)
0.066
Time-updated IL-6 (per 1 log, pg/ml higher)
2.06 (1.12, 3.77)
0.020
1.88 (1.02, 3.47)
0.042
Baseline sICAM-1 (per 1 log, ng/ml higher)
8.28 (1 93, 35.59)
0.004
6.13 (1.51, 24.78)
0.011
Time-updated sICAM-1 (per 1 log, ng/ml higher)
Baseline sTNF-RI (per 1 log, pg/ml higher)
4.45 (1.18, 16.68)
10.24 (2.08, 50.32)
0.027
0.004
3.66 (1.03, 13.08)
6.25 (1.17, 33.36)
0.046
0.032
3.55 (0.98, 13.56)
0.053
Time-updated sTNF Rl (per 1 log, pg/ml higher)
12.83 (1.99, 82.59)
0.007
3.03 (1.04, 8.79)
0.041
1.47 (0.34, 6.43)
0.51
1.76 (0.47, 6.62)
0.40
18.14 (2.94, 112.01)
0.002
11.58 (1.81, 73.92)
0.010
Baseline sTNF-RII (per 1 log, pg/ml higher)
3.45 (1.28, 9.33)
0.015
2.89 (0.99, 8.46)
0.052
Time-updated sTNF-RII (per 1 log, pg/ml higher)
3.51 (1.27, 9.67)
0.015
2.98 (1.03, 8.60)
0.044
Baseline sVCAM 1 (per 1 log, ng/ml higher)
2.29 (0.59, 8.92)
0.23
1.92 (0.47, 7.75)
0.36
Time-updated sVCAM 1 (per 1 log, ng/ml higher)
1.77 (0.41, 7.64)
0.45
15.9 (0.36, 6.98)
0.54
Baseline TNF-a (per 1 log, pg/ml higher)
2.28 (0.67, 7.78)
0.19
2.17 (0.61,7.79)
0.23
Time-updated TNF-a (per 1 log, pg/ml higher)
1.94 (0.54, 6.98)
0.31
1.78 (0.47, 6.74)
0.40
Biomarker Association with AIDS-Defining Events.
72
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Table 2.
Track B Clinical Science
Baseline and Time-updated Biomarker Association with Non-AIDS-Defining Events
Unadjusted
Biomarker
HR (95% CI)
Baseline CD4, NRTI and
Time-Updated CD4, NRTI
NNRTI/PI Adjusted
and NNRTI/PI Adjusted
p-value
HR (95% CI)
p-value
0.008
HR (95% CI)
p-value
1.16 (0.81, 1.65)
0.42
0.99 (0.52, 1.87)
0.97
Baseline hsCRP (per 1 log, ug/ml higher)
1.66 (1.15, 2.41)
0.007
1.66 (1.14, 2.43)
Time-updated hsCRP (per 1 log, ug/ml higher)
1.15 (0.81, 1.64)
0.44
1.16 (0.81, 1.67)
0.41
Baseline IL-6 (per l log, pg/ml higher)
1.68 (0.96, 2.93)
0.068
1.81 (1.01, 3.25)
0.047
Time-updated IL-6 (per 1 log, pg/ml higher)
0.96 (0.51, 1.83)
0.91
1.01 (0.53, 1.93)
0.97
Baseline sICAM-1 (per 1 log, ng/ml higher)
0.81 (0.53, 1.24)
0.33
0.79 (0.51, 1.22)
0.28
Time-updated sICAM-1 (per 1 log, ng/ml higher)
0.89 (0.55, 1.44)
0.64
0.88 (0.55, 1.42)
0.61
0.89 (0.55, 1.44)
0.65
Baseline sTNF-RI (per 1 log, pg/ml higher)
Time-updated sTNF Rl (per 1 log, pg/ml higher)
1.31 (0.24, 7.26)
2.58 (0.34, 19.84)
0.75
0.36
1.69 (0.27, 10.69)
3.06 (0.36, 25.89)
0.58
0.31
2.55 (0.31, 20.76)
0.38
Baseline sTNF-RII (per 1 log, pg/ml higher)
1.66 (0.69, 4.01)
0.26
1.98 (0.81, 4.87)
0.14
2.14 (0.77, 5.97)
0.15
2.14 (0.59, 7.83)
0.25
3.87 (1.34, 11.18)
0.012
Time-updated sTNF-RII (per 1 log, pg/ml higher)
2.07 (0.76, 5.61)
0.15
2.32 (0.84, 6.40)
0.11
Baseline sVCAM 1 (per 1 log, ng/ml higher)
1.03 (0.32, 3.32)
0.95
1.16 (0.35, 3.85)
0.81
Time-updated sVCAM 1 (per 1 log, ng/ml higher)
2.14 (0.60, 7.55)
0.24
2.22 (0.62, 7.95)
0.22
Baseline TNF-a (per 1 log, pg/ml higher)
2.33 (0.80, 6.76)
0.12
2.35 (0.83, 6.66j
0.11
Time-updated TNF-a (per 1 log, pg/ml higher)
3.75 (1.31, 10.77)
0.014
4.01 (1.39, 11.55)
0.010
Biomarker Association with NONAIDS-Defining Events.
associated with increased risk of non-AIDS-defining events, even
after adjustment for ART, baseline and changes in CD4 and
HIV-1 RNA.
Conclusion: Higher levels of several inflammatory biomarkers
were associated independently of CD4 count with increased risk of
AIDS and non-AIDS events. Larger and longer studies should
investigate the use of these markers as predictors of clinical
endpoints.
B53 - Ageing in persons with HIV
THAB0205
Comorbidity and ageing in HIV-1 infection: the AGEhIV
Cohort Study
J. Schouten1,2,3, F.W. Wit1,2,4, I.G. Stolte5, M. van der Valk4,
S.E. Geerlings4, F. de Wolf6, M. Prins5, P. Reiss1,2,4 and on behalf of
the Agehiv Cohort Study Group
1
Academic Medical Center (AMC), Global Health, Amsterdam,
Netherlands. 2Amsterdam Institute for Global Health and
Development (AIGHD), Amsterdam, Netherlands. 3Academic
Medical Center (AMC), Neurology, Amsterdam, Netherlands.
4
Academic Medical Center (AMC), Infectious Diseases, Amsterdam,
Netherlands. 5Public Health Service Amsterdam, Infectious Diseases
Research, Amsterdam, Netherlands. 6HIV Monitoring Foundation,
Amsterdam, Netherlands
Presenting author email: j.schouten@amc.nl
Background: HIV-positive patients may be at increased risk of
premature onset of age-associated non-communicable comorbidity
(AANCC).
Methods: Comprehensive assessment for AANCC in an ongoing
prospective cohort study of HIV-1-infected patients ]45 years from
a tertiary care HIV-outpatient clinic, and concurrently recruited
HIV-uninfected public sexual health clinic-attendants, comparable
regarding age, gender, ethnicity and risk-behavior. Baseline data on
AANCC (blood pressure ]140/90 mmHg, FEV1/FVCB0.7 and/or
self-reported by standardized questionnaire) were analyzed.
Results: Baseline characteristics from the first consecutively enrolled
381 HIV-positive and 349 HIV-negative subjects are listed in the tables.
Age (years)
Male gender
Dutch
MSM
Smoking (packyears)
Current smokers
Alcohol abuse
XTC abuse
HIV neg
(n349)
HIV pos
(n381)
p-value
51.7 (47.558.1)
84.2%
81.7%
65.0%
3.0 (0.019.0)
22.6%
7.2%
9.5%
53.1 (48.559.8)
90.6%
75.9%
71.7%
7.6 (0.030.8)
31.8%
2.9%
4.2%
0.022
0.010
0.307
0.055
0.011
0.006
0.008
0.005
* Data presented as median (IQR) or percentage as appropriate
Demographic and general characteristics.
HIV pos (n381)
Years documented HIV-1
seropositive (years)
Mean CD4 count in year prior
to enrollment (cells/mm3)
Nadir CD4 count (cells/mm3)
HIV-RNAB40 copies/mL
during year prior to
enrollment
Prior AIDS
On cART
Years since start of first ART
(years)
12.4 (6.817.5)
548 (421728)
330 (230450)
84.3%
21.0%
92.4% (67.2% started from naive
and 25.2% started ART-experienced)
11.4 (5.314.9)
* Data presented as median (IQR) or percentage as appropriate
HIV-related characteristics.
73
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track B Clinical Science
In every age-stratum the mean number of AANCC was higher among
HIV-positives. Similar patterns of AANCC burden appeared to occur
5 years earlier among HIV-positive patients than HIV-negative
subjects (Figure 2).
By ordinal logistic regression analysis, after adjustment for age,
gender and packyears of smoking, longer documented duration of
HIV-seropositivity was associated with a significantly higher risk of an
increasing number of AANCC (OR 1.17 per 5 years, 95% CI 1.071.27,
p0.0003).
Among HIV-positive patients, after adjustment for age, gender and
packyears of smoking, duration of ART-use (OR 1.24 per 5 additional
years of ART-use, 95% CI 1.061.46, p0.009) and lower nadir CD4
count (OR 1.12 per 100 less cells, 95% CI 0.991.28, p 0.074) were
each associated with an increased risk of a higher number of
AANCC, whereas documented duration of infection was no longer
significant.
Conclusion: In HIV-positive persons]45 years of age non-communicable comorbidity was more prevalent compared to controls,
and the risk of having an increased number of comorbidities was
independently associated not only with age and smoking history, but
also with duration of ART-use and severity of documented prior
immunodeficiency.
Prevalence of different AANCC.
B57 - Eradication / reservoir depletion
TUAE0104
HIV cure strategies: how good must they be to improve on
current antiretroviral therapy?
P. Sax1,2, A. Sypek3, B. Morris3, E. Losina1,2,4, A.D. Paltiel5, G. Seage6,
R. Walensky1,2,3, M. Weinstein6, J. Eron7,8 and K. Freedberg1,3,6
1
Harvard Medical School, Boston, United States. 2Brigham and
Women’s Hopsital, Boston, United States. 3Massachusetts General
Hospital, Boston, United States. 4Boston University School of Public
Health, Boston, United States. 5Yale School of Medicine,
New Haven, United States. 6Harvard School of Public Health, Boston,
United States. 7Gillings School of Global Public Health,
University of North Carolina, Chapel Hill, United States. 8University of
North Carolina School of Medicine, Chapel Hill,
United States
Presenting author email: psax@partners.org
Distribution of number of AANCC over age categories.
74.5% of HIV-patients and 61.6% of controls self-reported ]1
AANCC (p B0.001). The mean number of AANCC was 1.4 and 1.0,
respectively (p B0.001). Individual AANCC are shown in Figure 1.
Favorable Strategies
Background: The report of a successful HIV cure after allogeneic
bone marrow transplant for acute leukemia has generated major
interest in HIV eradication. We examined the efficacy, cost, and
relapse rate combinations that would make ‘cure’ cost-effective
compared with antiretroviral therapy (ART).
Discounted Cost ($) LMs (life months) QALMs (quality-adjusted life months) Incremental C-E Ratio ($/QALY)
GeneRx $50k
Efficacy 20%, relapse 0.5%
564,300
223.98
194.09
ART Strategy
GeneRx $100k
579,990
223.72
193.79
Dominated
ART Strategy
579,990
223.72
193.79
Efficacy 30%, relapse 0.5%
590,000
225.09
195.09
92,500
Efficacy 50%, relapse 0.1%
566,960
227.31
197.17
ART Strategy
579,990
223.72
193.79
Dominated
GeneRx $200k
Favorable Strategies for GeneRx.
74
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Favorable Strategies
Track B Clinical Science
Discounted Cost ($) LMs (life months) QALMs (quality-adjusted life months) Incremental C-E Ratio ($/QALY)
Chemo $144k
ART Strategy
579,990
223.72
193.79
Efficacy 30%, relapse 0.3%
586,410
224.80
194.90
69,300
579,990
585,370
223.72
228.74
193.79
198.49
13,700
Chemo $288k
ART Strategy
Efficacy 60%, relapse 0.1%
Chemo $432k
ART Strategy
579,990
223.72
193.79
Efficacy 90%, relapse 0.1%
617,880
232.37
201.78
56,900
Favorable Strategies for Chemo.
Thresholds for Cost-Effectiveness.
Methods: We used a Monte Carlo simulation of HIV disease (CEPAC
model) to assess the impact of suppressive ART either continued
indefinitely, or followed by one of three hypothetical strategies for
HIV eradication: gene therapy (GeneRx), chemotherapy to activate
the latent viral reservoir (Chemo), and an allogeneic bone marrow
transplant (BMT). Patients eligible for inclusion in the model were
virologically suppressed on first-line ART for one year. Patients who
relapsed after a cure strategy restarted on ART. For each strategy we
examined combination rates of cure, upfront cost, and monthly
relapse rates to determine benchmarks for which the eradication
strategies would compare favorably to ART. Model outcomes included projected life expectancy in months (LMs), cost, and
discounted (3%) cost-effectiveness (C-E) in $US/QALY using a C-E
threshold ofB$100,000/QALY.
Results: GeneRx would be C-E at 20% efficacy and 0.5% relapse
if it cost $50,000, at 30% efficacy and 0.5% relapse if it cost $100,000,
and 50% efficacy and 0.1% relapse if it cost $200,000 (Figure 1).
Chemo would be C-E at 30% efficacy and 0.3% relapse if it cost
$144,000, and at 60% efficacy and 0.1% relapse if it cost $288,000.
Both interventions could be cost-saving if relapse rates were low
enough. BMT was associated with decreased survival due to high
initial mortality.
Conclusion: A lower-risk HIV cure strategy, such as GeneRx, must be
at least moderately effective to compare favorably to current ART.
Higher risk approaches such as chemotherapy need to be even more
effective. These results can help frame targets for efficacy, durability,
and cost as such strategies are investigated.
Abstract Coding Guide
Example: MOAA01(Weekday) MO (Session type) AA (Session order) 01
Weekdays: SU (Sunday), MO (Monday), TU (Tuesday), WE (Wednesday), TH (Thursday), FR (Friday)
Session types: oral abstract sessions AA (Track A), AB (Track B), AC (Track C), AD (Track D), AE (Track E), AX (Cross-Track), LBA (Late
Breaker Track A), LBB (Late Breaker Track B), LBC (Late Breaker Track C), LBD (Late Breaker Track D), LBE (Late Breaker Track E), LBX (Late
Breaker Cross-Track); oral poster discussions sessions PDA (Track A), PDB (Track B), PDC (Track C), PDD (Track D), PDE (Track E) PDX
(Cross-Track)
Session order: 01, 02, 03, 04, etc.
75
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
http://www.jiasociety.org/index.php/jias/article/view/18440 | http://dx.doi.org/10.7448/IAS.15.5.18440
Track C Epidemiology and Prevention Science
C1 - Natural history, progression and
survival
C2 - Trends in morbidity and mortality
MOAC0205
WEPDB0104
HIV-1 outcompetes HIV-2 in dually infected Senegalese
subjects with low CD4 counts
1,2
2
3
4
3
D.N. Raugi , G.S. Gottlieb , P.S. Sow , S.L. Cherne , M. Toure ,
F. Sall3, F. Traore3, M.-P. Sy3, N.N. Zheng5, I. N’Doye6, N.B. Kiviat2,4,
S.E. Hawes1 and University of Washington-Dakar HIV-2 Study
Group
1
University of Washington School of Public Health,
Department of Epidemiology, Seattle, United States. 2University
of Washington School of Medicine, Department of
Medicine/Allergy & Infectious Diseases, Seattle, United States.
3
Clinique des Maladies Infectieuses, CHNU de Fann, Universite
Cheikh Anta Diop de Dakar, Dakar, Senegal. 4University of
Washington School of Medicine, Department of Pathology
Seattle, United States. 5Fred Hutchinson Cancer Research Center,
Vaccine and Infectious Disease Division, Seattle, United States.
6
Institut d’Hygiene Sociale, Conseil National de la Lutte contre le
SIDA, Dakar, Senegal
Presenting author email: raugid@u.washington.edu
Background: Dual infection with HIV-1 and HIV-2, which is not
uncommon in West Africa, has important implications for transmission, progression, and antiretroviral therapy. Few studies have
examined HIV viral dynamics in this setting.
Methods: We compared HIV-1 and HIV-2 viral loads from 65
dually infected, antiretroviral therapy-naı̈ve Senegalese subjects.
Participants provided demographic information and blood, oral fluid,
and cervicovaginal lavage (CVL) or semen samples for virologic and
immunologic testing. Associations between HIV-1 and HIV-2 levels in
plasma, PBMC, oral and genital samples were assessed using linear
regression models with generalized estimating equations to account
for subjects with multiple samples over time.
Results: In analyses adjusting for CD4 count, age, sex, and
commercial sex work, HIV-1 RNA levels were significantly higher
than HIV-2 levels in semen (b2.05 log10 copies/ml, 95% CI 0.44 to
3.66), CVL (b 1.37, 95% CI 0.83 to 1.91), and oral fluids (b 1.93,
95% CI 1.56 to 2.30). HIV-1 and HIV-2 PBMC viral DNA loads were
similar in those with normal immune function (CD4 counts above
500 cells/ml) (b 0.17 log10 copies/mg of PBMC DNA, 95% CI0.58 to
0.24), but compared to those with high CD4 counts, subjects with
CD4 counts below 500 cells/ml had higher HIV-1 and lower HIV-2
levels. In plasma, subjects with CD4 counts above 500 cells/ml had
mean HIV-1 plasma RNA viral loads 0.87 log10 copies/ml higher (95%
CI 0.35 to 1.38) than HIV-2, while among subjects with CD4 counts
between 200 and 500 cells/ml or below 200 cells/ml, this difference
increased to 4.28 and 4.35 log10 copies/ml (95% CIs 2.51 to 6.04 and
2.67 to 6.04), respectively.
Conclusion: Our data are consistent with the hypothesis that with
decreasing CD4 counts and HIV disease progression, HIV-1 may outcompete HIV-2 in dually-infected individuals. This finding may help
explain the differences in epidemiology between HIV-1 and HIV-2.
Social disparities and mortality in a large metropolitan HIV
cohort
P. Messeri1 and M.A. Chiasson2
1
Columbia University Mailman School of Public Health, Sociomedical
Sciences, New York, United States. 2Public Health Solutions,
New York, United States
Presenting author email: pam9@columbia.edu
Background: Evidence is mixed on the emergence of social
disparities that may have accompanied the dramatic decline in
mortality following the introduction of HAART in 1996. We
investigate disparities in mortality with regard to gender,
race/ethnicity and education during the first decade of the
21st century for three New York City (NYC) Metropolitan area
cohorts.
Methods: Data are pooled for three cohorts. One cohort was
recruited in NYC agencies in 1994 and remained active through
2001 (N 698). A second NYC cohort was recruited in 2002
(N 693) and remains active. A third cohort was recruited in 2001
from agencies located in three New York counties north of NYC
(N 398). Demographic data were obtained from baseline interviews. Date of death through 2009 was ascertained through a
search of an online death registry. Causes of death were obtained
for the two NYC cohorts from death certificates. Excess mortality
was estimated by matching cohort mortality rates to NYC death
rates on age, gender and race/ethnicity for 20032008. Mortality disparities were estimated using Cox proportional hazard
models.
Results: Despite a sharp decline in mortality following HAART
(Figure 1), the study cohort death rate of 33.2/1,000 person-years,
Figure 1.
76
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
for 20032008, was 28.1 deaths/1,000 person-years in excess
of the expected 5.1 death rate for a matched NYC general
population. Excess mortality was particularly high for Hispanics
(Table 1).
Table 1. Observed and Excess Mortality
Observed
Expected
Excess
Deaths/
Deaths/
Deaths/
1,000
1,000
1,000
Person-Years
Person-Years
Person-Years
Male
37.6
6.4
31.2
Female
27.6
3.5
24.1
African
33.5
6.3
27.2
American
Hispanic
35.5
3.5
32.0
White/Other
26.9
4.1
22.8
With respect to disparities, educational attainment proved to be a
stronger basis for mortality differences than race/ethnicity or gender
(Table 2).
Table 2.
Multivariate Hazard Ratios
Hazard Ratio
(95% C.I.)
Gender
Female
1.00
Race/Ethnicity
Male
White/Other
1.28 (1.021.60)
1.00
Education
African American
1.28 (0.921.80)
Hispanic
1.32 (0.931.89)
Less than H.S.
1.43 (1.101.87)
H.S. Diploma
1.28 (0.941.72)
Some College
1.00
Finally, an analysis of cause specific deaths found that a smaller
proportion of whites than African Americans or Hispanics died from
opportunistic infections.
Conclusion: To further reduce mortality rates and disparities for
HIV populations efforts should focus on maintaining current
initiatives to improve patient engagement in HIV medical care
coupled with support for medication adherence, while improving
coordination with treatment for preventable deaths from other
chronic conditions.
MOAC0301
Recent trends in and predictors of non-AIDS death in a
national cohort of HIV-diagnosed adults
M. Kall, R. Smith, A. Brown and V. Delpech
Health Protection Agency, HIV/STI Department, London, United
Kingdom
Presenting author email: meaghan.kall@hpa.org.uk
Background: Mortality among people living with HIV remains
high despite a decline in AIDS deaths since effective therapy. We
investigate recent trends and predictors of non-AIDS related causes
of deaths in a national cohort of people accessing HIV care.
Methods: Analysis of national HIV surveillance data of adults (aged
15) diagnosed with HIV between 19972010 in England & Wales.
Death reports were linked to the Office for National Statistics and
underlying causes of death were categorised into AIDS, non-AIDSrelated cancers, non-AIDS-related infections, liver disease, cardiovascular disease and stroke (CVD), accident/suicide, and other causes.
Cox regression models were fitted to identify significant (p B0.05)
predictors of non-AIDS deaths and adjusted hazard ratios (HR).
Results: Of 70,906 persons diagnosed from 1997 to 2010, 3,815
(5.4%) died during 318,620 person-years of follow up. 1,865 (51%)
died due to non-AIDS-related causes; increasing as a proportion from
48% of all deaths in 2000 to 59% in 2010. The most frequently
reported causes of death werenon-AIDS-related infections (448,24%)
(286 pneumonia, 115 septicaemia, 47 other respiratory infections),
CVD (309,17%), non-AIDS-related cancers (283,15%), accident or
suicide (267,14%), liver diseases (144,8%), and other causes (414,
22%). predictors of non-AIDS related death were injecting drug use
(HR 4.2[3.55.0], late diagnosis (CD4 B350cells/ul) (HR 1.2 [1.1
1.3]),B3 years exposure to HAART (HR 3.1[2.83.5]) and previous
AIDS diagnosis (HR 2.1[1.92.4]). In 2010, non-AIDS related mortality
rate was 3.6 per 1,000 HIV diagnosed persons age 1559, compared
to 1.6 per 1,000 in the general population age 1559 of England and
Wales.
Conclusion: Non-AIDS deaths account for half of deaths among HIVinfected adults and rates are double those of the general population.
Late diagnosis and a history of AIDS were strong predictors of nonAIDS related deaththis requires further investigation. Prompt HIV
care could reduce all-cause mortality of people living with HIV, not
only AIDS-related deaths.
C3 - Modelling HIV epidemics
MOAC0403
Estimation of HIV sexual transmission potential from IDU to
general population in two Russian cities
K. Eritsyan1,2, O. Levina1, T. Smolskaia3, E. White4 and R. Heimer4
1
NGO of Social Projects in the Sphere of Population’s Well-Being
‘‘Stellit’’, Saint-Petersburg, Russian Federation. 2Saint-Petersburg
State University, Department of Psychology, Saint-Petersburg,
Russian Federation. 3Saint Petersburg Pasteur Institute, SaintPetersburg, Russian Federation. 4Yale School of Public Health and
Center for Interdisciplinary Research on AIDSYale University,
New-Haven, United States
Presenting author email: ksenia@ngostellit.ru
Background: HIV epidemic in Russia remains concentrated mostly
among injection drug users (IDUs). Little is known about the extent
to which sexual partnerships bridge between IDUs and the general
population and create the potential for epidemic generalization.
Methods: IDUs in two Russian cities, Novosibirsk and Ivanovo
(N 593) were recruited via respondent-driven sampling. A modified
one-step snowball strategy was used to recruit IDU’s sex-partners
who do not themselves use drugs (PIDU, N82). Sexual behaviors of
all participants were assessed using an interviewer-administered
questionnaire. All participants provided blood specimens for HIV and
HCV testing.
Results: In Ivanovo HIV prevalence among IDUs was 34% and among
PIDUs - 6.8% (p 50.001). In Novosibirsk the corresponding prevalences were lower- 3.8% and 8.7% (n.s.). In both cities large
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Journal of the International AIDS Society 2012, 15 (Suppl 3)
proportions of IDUs reported sexual partnerships with non-IDUs 49.7% in Ivanovo vs. 62.7% in Novosibirsk (p50.001) and fewer than
1 in 4 IDUs reported constant condom use in such partnerships.
PIDUs in Novosibirsk also tended to have other sexual relationships
with non-IDU (52.2%) while in Ivanovo this behavior was less
common (6.8%; p 50.001). Based on the proportion of IDUs and
their sex-partners reporting sexual connections with non-IDUs
and mean number of such partners, we estimate that for every
100 IDUs in Ivanovo there are about 70 linked PIDUs and about
14 PIDUs downstream sex-partners from general population. For
Novosibirsk the corresponding estimates are much greater 118 and
95 respectively.
Conclusion: This pilot study results shows that two IDU populations
with significantly different HIV prevalence both form sexual partnerships with non-IDUs and practice unsafe sexual behavior within such
type of partnerships. However the proportion of PIDUs who form
partnerships with other non-IDUs that therefore could lead to
epidemic generalization is very different between two cities and
this difference needs to be considered when estimating the spread of
HIV into the general population.
TUAC0505
Decline in incidence of HIV and hepatitis C virus infection
among injecting drug users in Amsterdam: evidence for
harm reduction?
A.S. de Vos1, J.J. van der Helm2, M. Prins2,3 and M.E.E. Kretzschmar4,5
1
University Medical Center UtrechtJulius Center, Utrecht,
Netherlands. 2Public Health Service, Amsterdam, Netherlands.
3
Academic Medical Center (AMC), Amsterdam, Netherlands.
4
University Medical Center Utrecht, Utrecht, Netherlands. 5Centre
for Infectious Disease Control, RIVM, Bilthoven, Netherlands
Presenting author email: avos4@umcutrecht.nl
Background: Among injecting drug users (IDU) in Amsterdam
HIV prevalence has nearly halved since 1990. Incidence of both
HIV and Hepatitis C Virus (HCV) has declined very strongly, recently
nearing zero. As previously suggested in van den Berg et al., one
possible explanation is the large scale implementation of harm
reduction measures aiming to reduce risk behavior of IDU. However,
other factors could have influenced transmission. Most notably,
fewer individuals started injecting drugs in more recent decades, so
that population size decreased while average age has increased.
Methods: We used individual based modeling to explore the
transmission dynamics in this IDU population. Information about
demographic parameters was obtained from the Amsterdam Cohort
Study (ACS) among drug users. Our model includes changes in
recruitment and death rates over time, the latter dependent on age
and time since HIV-seroconversion. We considered the impact of
combination AntiRetroviral Treatment (cART) and different scenario’s
of risk behavior.
Results:
Track C Epidemiology and Prevention Science
. Introduction of cART lowers HIV incidence, but, by
increasing survival of HIV positive individuals, increases
HIV prevalence.
Conclusion: Observed trends in incidence and prevalence of HCV and
HIV in IDU in Amsterdam can almost exclusively be explained by
demographic changes in the population over time. More generally,
as the impact of harm reduction cannot easily be shown unequivocally in ecological studies, controlled intervention studies are
needed to quantify its effect.
MOPDC0201
Ageing with HIV in sub-Saharan Africa
J.A.C. Hontelez1,2,3, S.J. de Vlas1, R. Baltussen3, R. Bakker1, F. Tanser2,
M.N. Lurie4 and T. Bärnighausen2,5
1
Erasmus MC, University Medical Center Rotterdam, Public Health,
Rotterdam, Netherlands. 2Africa Centre for Health and Population
StudiesUniversity of KwaZulu-Natal, Mtubatuba, South Africa.
3
Radboud University Nijmegen Medical Center, Nijmegen
International Center for Health Systems Research and Education
(NICHE), Nijmegen, Netherlands. 4Brown University Warren Alpert
School of Medicine, Providence, United States. 5Harvard School of
Public Health, Department of Global Health and Population, Boston,
United States
Presenting author email: j.hontelez@erasmusmc.nl
Background: Antiretroviral treatment (ART) coverage is rapidly
expanding in sub-Saharan Africa (SSA). Based on the extended
survival of HIV-infected people and the reduced transmission, the
age composition of the HIV epidemic in the region will change in the
coming decades. We quantify the change of the age composition of
HIV-infected people in 43 countries in SSA.
Methods: We used STDSIM, a stochastic microsimulation model,
and developed a general approach to represent HIV prevalence and
treatment coverage in 43 SSA countries, using publicly available data.
We predict future trends in HIV prevalence and total number of
infections among population aged 1549 and 50 years and older for
different ART coverage levels.
Results: If treatment coverage continues to increase at present rates,
overall HIV prevalence in SSA in the population aged 1549 will
decline from 5% in 2011 to 3% in 2040, while prevalence in the
population aged 50 will increase from 3% to 4%, and these trends
are universal for all countries in SSA (Figure 1). The total number of
HIV-infected patients aged 50 will nearly triple over the coming
yearsfrom 3.1 million in 2011 to 9.1 million in 2040, dramatically
. Without assuming risk behavior change over time (i.e.
effects of harm reduction), we can reproduce main trends
in HIV and HCV prevalence and incidence.
. HIV prevalence decline in our model is partially explained
by a decrease in the number of high risk individuals in the
population, caused by HIV related mortality.
. Fast HIV decline and a slight decline in HCV prevalence
in the mid 1990’s may be indicative of changes in individual risk behavior, possibly related to harm reduction
intervention.
Figure 1.
HIV prevalence by age in SSA.
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
of Lilongwe, Malawi belongs to a stable partnership. Among
the stable partnerships, an estimated 5.0% (3.2%11.7%) are HIVdiscordant, 94.4% (85.5%96.3%) are concordant-negative, and 0.6%
(0.5%3.0%) are concordant-positive. Only 4.5% (3.3%39.5%) of
all incident infections are estimated to occur within stable, HIVdiscordant partnerships annually.
Conclusion: The small proportion of transmission events occurring
within stable, HIV-discordant couples in our model suggests that
interventions targeted specifically to this group should be complemented by strategies reaching other targets.
Figure 2. Trend in total number of infections.
changing the age composition of the HIV epidemic in SSA (Figure 2).
In 2011, about 1 in 7 HIV-infected patients was aged over 50 years; in
2040, this ratio will be larger than 1 in 4.
Conclusion: We show that the HIV epidemic in SSA will rapidly age
over the coming decades. This has important consequences for
both the organization of health care services and the general
organization of societies in the sub-continent, as older HIV-infected
patients require specialized treatment and care, as well as social
and financial support. In addition, expanded treatment coverage is
likely to increase the burdens of other diseases in SSA, in particular
NCDs.
TUPDC0204
The contribution of HIV-discordant couples to HIV
transmission in Lilongwe, Malawi
K. Powers1, A. Ghani2, W. Miller1, I. Hoffman1, A. Pettifor1,
M. Hosseinipour1,3, G. Kamanga3, F. Martinson3 and M. Cohen1
1
University of North Carolina at Chapel Hill, Chapel Hill, United
States. 2Imperial College London, London, United Kingdom. 3UNC
Project Malawi, Lilongwe, Malawi
Presenting author email: powersk@email.unc.edu
Background: HIV-discordant couples represent possible targets
for HIV transmission prevention strategies, such as pre-exposure
prophylaxis and ‘‘treatment as prevention.’’ However, the population-level impact of such strategies on HIV incidence will depend on
the relative contribution of discordant couples to HIV spread in a
given setting.
Methods: We used a deterministic, compartmental model to
estimate the proportion of incident HIV cases arising within stable
discordant partnerships in Lilongwe, Malawi. The model, which was
based on detailed behavioral and viral load data from a sexually
transmitted infections clinic in Lilongwe, included sexual contact
within and outside of steady partnerships, as well as changes in HIV
transmissibility across infection stages. We used a Bayesian melding
approach to fit the model to empirical HIV prevalence estimates, to
account for input uncertainty, and to calculate 95% credible intervals
around model outputs. The best-fitting model included a ‘‘lower-risk’’
and a ‘‘higher-risk’’ group, with average partnership lengths of
2.5 years and 1.3 months, respectively. We considered partnerships
in the lower-risk group to represent stable partnerships. Among
those stable partnerships, we estimated the proportions that are
currently HIV-discordant, HIV-concordant-negative, and HIV-concordant-positive. We also calculated the proportion of all incident cases
arising within the stable, HIV-discordant couples.
Results: Based on the best-fitting (i.e., the mode) model simulation,
48.5% (95% credible interval 48.4%75.2%) of the adult population
WEPDC0106
Population-level benefits from providing effective HIV
prevention means to pregnant women in high prevalence
settings
D. Dimitrov1, M.-C. Boily2, J. Marrazzo3 and E. Brown1
1
Fred Hutchinson Cancer Research Center, Vaccine & Infectious
Disease Division, Seattle, United States. 2Imperial College London,
Department of Infectious Disease Epidemiology, London, United
Kingdom. 3University of Washington, Division of Allergy & Infectious
Diseases, Seattle, United States
Presenting author email: dobromir@scharp.org
Background: HIV prevalence among pregnant women in Southern
Africa is extremely high. Some studies suggest that sexual risk of HIV
acquisition during pregnancy is doubled and that infected women
may be more likely to transmit HIV to male partners. Also, the
association between high maternal viral load implies that HIV
infections acquired during pregnancy carry higher risk of motherto-child transmission (MTCT). We analyze the potential benefits from
extending HIV prevention to pregnant women in addition to nonpregnant women using wide-scale microbicide interventions as an
example.
Methods: A transmission dynamic model is designed to assess the
impact of microbicide usage in high HIV prevalence settings and
estimate prevented cumulative fractions of new HIV infections (CPF),
fractions of infections acquired during pregnancy, and fractions of
MTCT over 10 years.
Results: Consistent use of 70% efficacious microbicide by 60% of the
non-pregnant women may prevent 3639% and 11% new infections
in women and men over 10 years, respectively, assuming no increase
in sexual HIV risk to either partner during pregnancy (RRsex/preg 1).
It may also prevent 510% MTCT depending on the increase in MTCT
risk when HIV is acquired during pregnancy compared to before
pregnancy (RRMTCT/preg). The usage of microbicides by pregnant
women may increase the absolute CPF by 5% (RRsex/preg 1) to 10%
(RRsex/preg 2) and reduce the number of HIV infections during
pregnancy by 40% to 70% in different scenarios. It may add between
5% (RRsex/preg 1, RRMTCT/preg 1) and 22% (RRsex/preg 2, RRMTCT/
preg 4) reduction in MTCT.
Conclusion: Providing HIV prevention tools to pregnant women in
the context of wide-scale interventions would be desirable as it
would help to increase the effectiveness of the intervention,
especially if sexual risk during pregnancy is elevated. It would
significantly reduce the number of HIV infections acquired during
pregnancy and help prevent MTCTs but should not be a substitute for
PMTCT.
THPDC0102
Modeling of HIV epidemic among men who have sex with
men in Beijing, China
79
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
H.-Z. Qian1, J. Lou2, Y. Ruan3, G.F. Webb4, Y. Shao3 and S. Vermund1
1
Vanderbilt Institute for Global Health, Nashville, United States.
2
Shanghai University, Department of Mathematics, Shanghai
China. 3National Center for AIDS/STD Control and Prevention,
China CDC, Division of Virology and Immunology, Beijing, China.
4
Vanderbilt University, Department of Mathematics, Nashville,
United States
Presenting author email: han-zhu.qian@vanderbilt.edu
Background: A sharp increase of HIV epidemic has been observed
among Chinese men who have sex with men (MSM) in the past 510
years, particularly in large cities like Beijing. China has implemented
intervention campaigns to tackle this problem, but the impacts are
unknown. We developed mathematical models for predicting the
trends of HIV epidemic among MSM in Beijing City under different
scenarios of interventions.
Methods: Deterministic HIV/AIDS models were developed in which a
Bernouilli process was used to assess the relationship between peract and per-partner anal intervention transmission probabilities over
a given number of sex acts. Data for estimating parameters came
from national and local HIV reporting and sentinel surveillance
networks, Chinese free ART project database, local epidemiological
studies and literature. Markov-chain Monte-Carlo simulations were
carried out using the Metropolis-Hastings algorithm to estimate
mean values of some parameters.
Results: The basic reproduction number is derived and a backward
bifurcation occurs for some situations, suggesting that the classical
Figure 1.
Impact of update of testing on HIV epidemic.
Figure 2. Impact of update of changing risky behaviors on HIV
epidemic.
Track C Epidemiology and Prevention Science
requirement for the basic reproduction number to be below unity,
though necessary, is not sufficient for disease control in this case.
HIV prevalence rate among MSM in Beijing will increase from
reported 1.2% in 2000, 7.8% in 2010 to projected 25% in 2020 if the
coverage and intensity of interventions remain same. Simulations
show that the sole intervention for increasing HIV testing will not
reverse the rising trend of HIV epidemic if MSM do not change their
risky sexual behaviors (Figure 1); while HIV epidemic can be reduced
if these men reduce their risky sexual behaviors even they have a
moderate level of HIV testing (Figure 2).
Conclusion: HIV epidemic will continue to rise rapidly among Chinese
MSM if no enhanced prevention interventions are implemented.
Integrated interventions for increasing HIV testing, risk reduction and
ART update and adherence are needed.
C4 - Risk factors for acquisition of HIV
MOAC0404
Risk profiles of injecting partnerships: correlates of
receptive syringe and cooker sharing among a cohort of
young injecting drug users in San Francisco, California
M. Morris1, J. Evans1, M. Yu1, A. Briceno1, K. Page1 and J. Hahn2
1
University of California at San Francisco, Epidemiology and
Biostatistics, San Francisco, United States. 2University of California at
San Francisco, Department of Medicine, San Francisco, United States
Background: It is increasingly recognized that HIV and hepatitis
C (HCV) risk, such as syringe sharing, occurs in the context of
relationships between (at least) two people.
Methods: In San Francisco from 2006 to 2011, we enrolled 53
injecting partnerships that were HCV-discordant at baseline based on
RNA testing. Partnerships were defined as having injected together
5 or more times in the prior month. Each partnership completed
monthly interviews for one year. Generalized linear models were
used to examine correlates of two outcomes (1) receptive syringe
sharing (RSS) and (2) receptive cooker-sharing (RCS) reported by the
HCV-negative partner.
Results: Participants had a median age of 26 (IQR:2328) and
median years injecting of 8 (IQR:310). Within partnerships, 62%
were female-male, 36% were male-male, 2% were female-female;
the median number of times per day partners injected together was
2 (IQR:13), 25% were sexual and injecting partnerships and 48%
lived together. RSS and RCS was more likely to occur in partnerships
that lived together (OR 2.27, 95% CI: 1.423.63; OR 2.79, 95%
CI: 1.704.58) and in sex and injection partnerships (OR 2.76, 95%
CI: 1.754.36; OR 2.50, 95% CI: 1.554.02); partnerships who lived
together and had sex were at even greater odds of risk (OR 4.15,
95% CI: 2.576.73; OR3.52, 95% CI: 2.205.65). Among partnerships who lived together, living within unstable housing (e.g., on the
street, park, or shelter) increased the risk for RSS (OR 2.22, 95% CI:
1.282.57) and RCS (OR 1.66, 95% CI: 1.702.36) compared to
partnerships who lived in an apartment, hotel, or group home.
Pooling money to purchase drugs also was positively associated with
both outcomes (OR 1.82, 95% CI: 1.383.58; OR 2.11, 95% CI
1.413.16). Duration of the relationship, gender composition of the
partnership, HIV-status, or HCV-status was not associated with either
of the outcomes.
Conclusion: Few studies have examined HIV-risk behaviors
within drug-using partnerships. Our results suggest that relationship
factors may influence risk within injecting partnerships and are
an important consideration in the design of relationship-based
interventions.
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
WEAC0101
Lost in transition: prevalence and correlates of HIV infection
among young men and women surviving abduction and
displacement in post-conflict northern Uganda
S. Patel1, M.T. Schechter1, H. Muyinda2, N. Kiwanuka3,
N.K. Sewankambo4 and P.M. Spittal1
1
University of British Columbia, School of Population and Public
Health, Vancouver, Canada. 2Makerere University, Child Health and
Development Centre, Kampala, Uganda. 3Makerere University,
School of Public Health, Kampala, Uganda. 4Makerere College
of Health Sciences, Office of the Principal, Kampala, Uganda
Presenting author email: spatel55@hotmail.com
Background: After more than two-decades of war and displacement
in Northern Uganda, over one million Internally Displaced Peoples
(IDPs) are returning to their home villages. However, thousands of IDPs
are only halfway home, living in transit camps near their villages. This
population in transition provided a unique opportunity to assess the
influence of conflict on HIV infection among young people surviving
displacement and abduction in post-conflict Northern Uganda.
Methods: In 2010, a cross-sectional demographic and behavioral
survey was conducted with 384 young people aged 1529, residing in
transit camps in one of two sub-counties in Gulu District. Biological
specimens for HIV were collected for Rapid testing in the field
and Confirmatory testing in a lab. Multivariable logistic regression
identified factors significantly associated with HIV infection.
Results: Of the 384 participants sampled, 192 (50%) were female and
107 (27.9%) were former child soldiers. Overall HIV prevalence was
alarmingly high at 12.8%. HIV prevalence among females was 15.6%,
9.9% among males, and 12.1% among former child soldiers. In
multivariable logistic regression, HIV positivity was significantly
associated withnon-consensual 1st sex (Adjusted Odds Ratio [AOR]:
9.9, 95% Confidence Interval [CI]: 1.7, 18.06); sub-county A (AOR: 2.9,
95%: CI1.3, 6.7); STI symptoms past 12 months (AOR: 2.4, 95%: CI1.4,
6.2); practicing dry sex (AOR: 2.3, 95%: CI1.0, 5.1); age (AOR: 1.2, 95%:
CI1.1, 1.3); thinking you could protect yourself from HIV (AOR: .29,
95%: CI.12, .69); and number of HIV tests in lifetime (AOR: .86, 95%:
CI.81, .91).
Conclusion: In post-conflict Northern Uganda it has been observed
that NGOs focused on relief who previously supported HIV/AIDS
prevention and treatment have shuttered operations, leaving gaps
in care. This, coupled with other strains of post-conflict resettlement,
has produced a generation of young people ‘lost in transition’,
leaving them at heightened risk of contracting HIV/AIDS. Applicable
post-conflict HIV/AIDS programming is urgently required.
C5 - Hormonal contraception and HIV
WEAC0201
Association between STI/RTI infections, altered cervical
innate immunity and HIV-1 seroconversion among
hormonal contraceptive users
R. Fichorova1, C. Morrison2, G. Doncel3, P.-L. Chen2, C. Kwok2,
T. Chipato4, R. Salata5 and C. Mauck6
1
Brigham and Women’s Hospital, Harvard Medical School,
Boston, United States. 2Family Health International (FHI 360),
Durham, United States. 3CONRAD, Eastern Virginia Medical School,
Norfolk, United States. 4University of Zimbabwe, Harare, Zimbabwe.
5
Case Western Reserve University, Cleveland, United States.
6
CONRAD, Eastern Virginia Medical School, Arlington, United States
Track C Epidemiology and Prevention Science
Background: Hormonal contraceptives (HC) have been associated
with risk of HIV-1 seroconversion in women and their partners. We
examined the association between injectable HC (DMPA), combined
oral contraceptives (COC), and no hormonal contraceptive use (NH)
with genital tract mucosal immunity biomarkers in women with STI/
RTI who did or did not become HIV infected.
Methods: Biomarkers were quantified in cervical swabs from 832
HIV-uninfected reproductive-aged Ugandan and Zimbabwean women
with documented HC use, HIV/STI behavioral risk factors, STI/RTI
signs and symptoms, and were correlated with HIV-1 seroconversion
at next visit. C. trachomatis (CT) and N. gonorrhoeae (NG) were
diagnosed by PCR, genital herpes by HSV-2 antibody ELISA, BV by
Nugent score, and candida by wet mount. Multivariable generalized
linear models utilizing Box-Cox power transformation examined
associations between levels of biomarkers and risk factors for HIV
infection (STIs including signs and symptoms, HC use). Odds ratios
with Breslow-Day test for homogeneity described the risk of having
top quartile concentrations of biomarkers in STI/RTI versus
negative women across HC groups.
Results: Women who had both signs and symptoms of STI/RTI
had higher beta-defensin (BD)2 and lower SLPI levels in cervical
secretions compared to STI-free women. Both of these changes were
associated with HIV seroconversion (occurring among 24% of women
at the next visit). Among women with BV, odds of top quartile BD2
levels were higher in the OC and DMPA users than in the NH group.
When compared to NH, DMPA use was associated with lower levels
of the anti-inflammatory regulator IL-1RA overall and, in women with
intermediary vaginal microflora, HSV-2 and NG, with significantly
lower odds of top quartile IL-1RA concentrations.
Conclusion: OC and DMPA differentially modulate levels of cervical
protective immune mediators, altering responses to STI/RTIs, and
providing insight into possible biological mechanisms for higher risk
of HIV acquisition.
WEAC0202
Association of injectable contraception and risk of HIV-1
acquisition in women in HIV-1 serodiscordant
partnerships: persistence of effect in multiple sensitivity
analyses
R. Heffron1, D. Donnell2, H. Rees3, C. Celum1, N. Mugo1,4, E. Were5,
G. de Bruyn3, E. Nakku-Joloba6, K. Ngure4, J. Kiarie1,4, R. Coombs1,
J. Baeten1 and Partners in Prevention HSV/HIV Transmission Study
Team
1
University of Washington, Seattle, United States. 2Fred Hutchinson
Cancer Research Center, Seattle, United States. 3University of
Witswatersrand, Johannesburg, South Africa. 4Kenyatta National
Hospital, Nairobi, Kenya. 5Moi University, Eldoret, Kenya. 6Makerere
College of Health Sciences, Kampala, Uganda
Presenting author email: rheffron@u.washington.edu
Background: We recently reported that women in HIV-1 serodiscordant partnerships using injectable contraceptives had a 2-fold
increase in HIV-1 acquisition risk (aHR 2.05, p0.04; Heffron
et al., Lancet Infectious Diseases 2012). Here, we report the results
from multiple additional sensitivity analyses examining the robustness of our findings.
Methods: We used Cox proportional hazards regression, adjusting
for age, male partner’s plasma viral load, and time-dependent
unprotected sex and pregnancy, to compare HIV-1 incidence in
women using injectable contraception to women reporting no
hormonal method. Sensitivity analyses included: 1) additional or
alternative covariates to adjust for sexual behavior, 2) restricting
to follow-up periods when unprotected sex was reported,
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
3) censoring visits after a woman switched her contraceptive method
(to minimize the effect of changing methods on risk), and 4)
restricting to consistent injectable users outside of South Africa
(with access to only injectable depot medroxyprogesterone acetate
[DMPA]).
Results: In all models, the approximately 2-fold increase in HIV-1
acquisition risk persisted. Neither additional adjustment for coital
frequency (aHR 2.06, p0.04) nor adjustment for the male
partner’s report of unprotected sex (where accuracy is less likely
influenced by the woman’s contraceptive choice, aHR 2.03,
p0.07) influenced the results. When limited to periods when
unprotected sex was reported or including only visits prior to the
first contraceptive switch, the aHR were 2.29 (p0.17) and 2.62
(p 0.07), respectively. Finally, when only consistent, presumed
DMPA users were retained (i.e. South Africans excluded), injectable
contraception was associated with a nearly 4-fold increased HIV-1
risk (aHR 3.93, p0.01).
Conclusion: Injectable contraception continued to be associated with
increased HIV-1 risk despite numerous methods to control for
potential imprecision in contraceptive exposure measurement and/
or key behavioral confounders. Some analyses had p-values 0.05
due to reduced statistical power but the magnitude of association
continued to be as strong as that seen in our primary analytic model.
WEAC0203
Hormonal contraception and HIV acquisition in women: a
systematic review of the epidemiological evidence
C. Polis1 and K. Curtis2
1
USAID, Office of Population and Reproductive Health, Washington,
United States. 2Centers for Disease Control and Prevention, Division
of Reproductive Health, Atlanta, United States
Presenting author email: cpolis@usaid.gov
Background: There are data suggesting that use of hormonal
contraception (HC) might affect the risk of HIV acquisition in HIVnegative women.
Methods: We conducted a systematic review of the epidemiological
literature on the association between HC and HIV acquisition. We
systematically searched for relevant articles in any language
published or in press by December 15, 2011, evaluated study quality,
assessed the association of study findings with various methodological features, and synthesized the evidence.
Results: We identified twenty relevant studies, eight of which met
minimum quality criteria. Of these, only one reported a statistically
significant association between use of oral contraceptive pills (OCPs)
and HIV acquisition. No studies reported statistically significant
associations between use of norethisterone enantate (Net-En)
and HIV acquisition, but data were limited. Estimates for depot
medroxyprogesterone acetate (DMPA) or non-specified contraceptive injectables and HIV acquisition were heterogeneous, and we
consider factors including analysis of condom-use information,
length of inter-survey interval, and analysis of serodiscordant couples
as possible reasons for heterogeneity.
Conclusion: Overall, current evidence does not suggest an association between OCP use and HIV acquisition. No currently available
evidence suggests an association between Net-En and HIV acquisition, though data are limited. Evidence assessing DMPA or nonspecified injectable contraception and risk of HIV acquisition is
inconsistent; it does not establish a clear causal association with HIV
acquisition, nor does it definitively rule out the possibility of an
effect. Concerns remain about the potential for residual confounding, even within otherwise high-quality studies. Many women at risk
of HIV have a critical need for safe and effective means of pregnancy
Track C Epidemiology and Prevention Science
and infection prevention, and it is imperative that clients and
providers are informed that HC does not protect against HIV or other
STIs.
WEAC0204
Hormonal contraception and HIV disease progression: a
systematic review of the epidemiological evidence
S. Phillips1, K. Curtis2 and C. Polis3
1
World Health Organization, Reproductive Health and
Research, Geneva, Switzerland. 2Centers for Disease Control &
Prevention, Division of Reproductive Health, Atlanta
United States. 3US Agency for International Development,
Office of Population and Reproductive Health, Washington
United States
Presenting author email: phillipss@who.int
Background: Prevention of unintended pregnancy remains a key
concern for women living with HIV, both as a core strategy to
prevent mother-to-child transmission of HIV and to decrease
maternal and neonatal morbidity and mortality through lower birth
rates, improved birth spacing, and lower rates of unsafe abortion.
However, there are theoretical concerns about the effect of various
contraceptive methods on HIV disease progression.
Methods: We conducted a systematic review to determine whether
HIV-infected women who use hormonal contraception are at
increased risk of HIV disease progression compared with those
who do not use hormonal contraception. We searched PUBMED and
EMBASE for articles published in peer-reviewed journals through
December 15, 2011 for evidence relevant to all hormonal contraceptive methods and HIV disease progression.
Results: Twelve reports of eleven studies met inclusion criteria.
One randomized controlled trial (RCT) found increased risk of a
composite outcome of declining CD4 count or death among
hormonal contraceptive users when compared with copper IUD
users. Ten observational studies reported no increased risk of HIV
disease progression, as measured by mortality, time to CD4 below
200, time to initiation of antiretroviral therapy, increased HIV-RNA
viral load, or decreased CD4 count with hormonal contraceptive use
compared with non-use.
Conclusion: One RCT found that hormonal contraceptive use
was associated with increased risk of HIV disease progression
when compared with IUD use, but this study had important
methodological shortcomings. Cohort studies consistently found
no association between hormonal contraceptive use and HIV disease
progression compared with non-use of hormonal contraceptives.
Thus, the preponderance of evidence indicates that HIV-positive
women can use hormonal contraceptive methods without concerns related to HIV disease progression. Prevention of unintended pregnancy through safe and effective contraceptive use
among women with HIV remains a public health priority to safeguard maternal health and prevent mother-to-child transmission
of HIV.
C6 - Risk factors for infectivity,
progression and transmission of HIV
WEAB0202
Racial disparities in antiretroviral therapy use and viral
suppression among sexually active HIV-positive men who
82
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
have sex with men receiving medical care: United States,
Medical Monitoring Project, 2009 data collection cycle
L. Beer, A. Oster, C. Mattson and J. Skarbinski
U.S. Centers for Disease Control and Prevention, Atlanta,
United States
Presenting author email: lbeer@cdc.gov
Background: In the United States, black men who have sex with men
(MSM) are substantially more likely to acquire HIV than white MSM.
Given highly racially homogeneous sexual networks, lower levels of
viral suppression in HIV-infected black MSM (due to differences in
antiretroviral [ART] use), might contribute to racial disparities in HIV
infection. We present the first nationally representative data on
disparities in ART use and viral suppression among sexually active
black and white MSM receiving care.
Methods: We used interview and medical record data collected
June 2009-May 2010 from the Medical Monitoring Project (MMP),
a national probability sample of HIV-infected adults receiving
medical care January-April 2009. We estimated the prevalence of
self-reported current ART use and clinical documentation of viral
suppression (most recent viral load 5200 copies/ml) among sexually
active non-Hispanic black MSM and white MSM. Analyses accounted
for clustering, unequal selection probabilities, and non-response.
Results: Of 4,217 eligible participants, 313 black MSM and 691 white
MSM were identified. Estimated national prevalence of ART use and
viral suppression for these subpopulations is shown in the Figure.
Black MSM were significantly less likely than white MSM to report
ART use (pB.001) and be virally suppressed (p B01).
Conclusion: Among sexually active MSM receiving care, there are
substantial racial disparities in ART use and viral suppression.
One-fifth of black MSM were not on ART and almost one-third
were not virally suppressed. These differences may contribute to
the racial disparity in new infections among MSM. Narrowing gaps
in ART use and viral suppression between HIV-infected black
and white MSM will reduce morbidity among HIV-infected black
MSM and might contribute to reducing new HIV infections among
uninfected black MSM.
Track C Epidemiology and Prevention Science
E. Kahle1, M. Campbell1, J. Lingappa1, D. Donnell2, C. Celum1,
S. Kapiga3, R. Ondondo4, N. Mugo1,5, A. Mujugira1, K. Fife6,
J. Mullins1, J. Baeten1 and Partners in Prevention HSV/HIV
Transmission Study
1
University of Washington, Seattle, United States. 2Fred Hutchinson
Cancer Research Center, Seattle, United States. 3London School of
Hygiene and Tropical Medicine, London, United Kingdom. 4Kenya
Medical Research Institute, Kisumu, Kenya. 5Kenyatta National
Hospital, Nairobi, Kenya. 6Indiana University, Bloomington,
United States
Presenting author email: ekahle@u.washington.edu
Background: HIV-1 subtype C is the most common subtype worldwide and the dominant subtype in southern Africa. It has been
hypothesized that increased transmissibility could explain the
explosive spread of subtype C in southern Africa. We assessed the
risk of heterosexual HIV-1 transmission in subtype C compared with
other subtypes among serodiscordant couples.
Methods: We performed a nested case-control study within a
multinational prospective cohort of stable HIV-1 serodiscordant
couples from 7 countries in eastern and southern Africa (Partners
in Prevention HSV/HIV Transmission Study). Cases were defined as
couples in which phylogenetically-linked HIV-1 transmission occurred
within the partnership; four controls for each case were selected
proportionally from non-transmitting couples by the study site and
gender distribution of the full study cohort. HIV-1 subtype in the HIV1 infected partner was determined through consensus partial env
and gag gene sequencing. We used an adjusted logistic regression to
calculate the odds of HIV-1 transmission by subtype C versus non-C
subtypes, controlling for gender, age and baseline unprotected sex.
Results: HIV-1 subtype distribution was comparable between cases
(N 123) vs. controls (N 459): subtype A (45% vs. 44%), subtype
C (38% vs. 39%), subtype D (15% vs. 14%), subtype G (1% vs. 1%),
and circulating recombinant forms (CRF, 2% vs. 3%). Subtype C was
not associated with an increased likelihood of HIV-1 transmission
(env adjOR 0.85, 95% CI 0.521.24, p0.3; gag adjOR 1.34, 95%
CI 0.862.10, p0.2). Further adjustment for plasma viral load did
not substantially change these risk estimates (env adjOR 0.80, 95% CI
0.511.23, p 0.3; gag adjOR1.27, 95% CI 0.802.00, p0.3).
Analyses comparing subtype C to other subtypes showed no
significant associations for HIV-1 transmission risk.
Conclusion: In this multinational study of HIV-1 transmission among
stable heterosexual African HIV-1 serodiscordant couples, we found
no evidence of increased transmission risk for subtype C in adjusted
analyses.
TUAC0104
Impact of antiretroviral therapy on HIV-positive status
disclosure in rural South Africa
Figure. Estimated percentage of HIV-infected adults receiving
medical care on antiretroviral therapy and with suppressed viral
load, among sexually active men who have sex with men
(MSM) by race Medical Monitoring Project (MMP) United States,
2009 Data Collection Cycle [Beer et al. IAC 2012 figure].
TUAC0101
HIV-1 subtype C is not associated with higher risk of
heterosexual transmission: a multinational study among
African HIV-1 serodiscordant couples
B. Bearnot1,2, L. Werner1, A. Kharsany1, S. Abdool Karim1,3,
J. Frohlich1 and Q. Abdool Karim1,3
1
CAPRISA, UKZN, Durban, South Africa. 2New York University, New
York, United States. 3Columbia University, New York, United States
Presenting author email: bibearnot@gmail.com
Background: HIV-positive individuals risk transmission to uninfected
sexual partners. This risk may be elevated in the absence of
disclosure of HIV status, but could be ameliorated given several
options to prevent sexual transmission once HIV status is known. The
purpose of this study was to assess the impact of antiretroviral
therapy (ART) on degrees of HIV status disclosure.
Methods: In this prospective cohort study, we enrolled consenting,
HIV-positive adults from the CAPRISA Vulindlela AIDS Treatment
programme into one of two armsART experienced or ART naı̈ve.
83
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
Table 1. Rates of HIV-positive disclosure by ARV arm and gender at enrollment and follow-up time points. Family disclosure refers
to all relatives, including those by marriage. Wide disclosure refers to friends, neibours, clergy, coworkers, community health
workers, and others. *Adjusted for age #Adjusted for age and gender
On ART (N 414)
Male
Female
Disclosure at Enrollment
(N132)
(N282)
Median Days to Disclosure (IQR)
Not on ART (N273)
Male
Female
P
P Value between
P Value*
(N 52)
(N 221)
Value*
arms#
0.838
1 (014)
1 (014)
0 (00)
0 (01)
0.140
Partner Disclosure %
45.5
25.2
B0.001
44.2
21.7
0.001
Family Disclosure %
77.3
92.6
B0.001
53.9
70.1
0.0670
Wide Disclosure %
27.3
21.3
0.137
9.6
14.0
0.464
On ART (N 362)
Disclosure at Follow-up
Male
Female
(N118)
(N244)
0.371
B0.00l
0.001
Not on ART (N174)
P Value*
Male
Female
P
P Value between
(N 33)
(N 141)
Value*
Arms#
Partner Disclosure %
17.8
7.8
0.005
24.2
13.5
0.160
0.053
Family Disclosure %
Wide Disclosure %
40.7
32.2
39.8
31.2
0.856
0.762
45.5
15.2
41.1
24.1
0.475
0.349
0.722
0.015
Disclosure of HIV status was not a prerequisite for care or treatment.
Data were collected at two time points using structured questionnaires including demographic, clinical, and HIV status disclosure
information.
Results: Between June 2006August 2009, 687 HIV-positive individuals were enrolled; 73.3% were female. At enrollment, 414
participants (60.3%) were on ART (median days on ART 54, IQR
11167; median CD4 138/mL, IQR 86199) and 273 (39.7%) were in
care but not eligible for ART (median CD4 346/mL, IQR 254476).
Disclosure was common in ART and non-ART groups, with ART
experienced participants more likely to have disclosed to at least one
person than ART naı̈ve individuals (99% versus 83.3%; pB0.001).
Disclosure occurred soon after HIV diagnosis (median01 day,
respectively).
Disclosure rates to sexual partners were markedly lower in both ART
and non-ART groups (31.6% and 26.0%), and was less common
among females compared to males (23.7% versus 45.1%; pB 0.001).
Low rates of further partner disclosure persisted at a median of 4.4
months post-enrollment (Females 9.9% versus Males 19.2%;
p0.003).
Conclusion: Patients on ART had higher rates of disclosure. HIVpositive individuals in both arms readily disclosed to family members
and wider social networks. Rates of disclosure to sexual partners
were much lower, particularly among female participants. This
represents an addressable risk for HIV transmission in serodiscordant partnerships.
TUAC0202
More frequent sexual risk behaviours among HIV-negative
sexually transmitted infection clinic patients compared to
HIV-positive and HIV-negative HIV testing and counseling
center patients in Lilongwe, Malawi
C. Mapanje1, S. Rutstein2,3, G. Kamanga1,3, S. Phiri4, D. Nsona4,
A. Pettifor5, N. Rosenberg5, I. Hoffman2 and W. Miller2,5
1
UNC Project-Malawi, Lilongwe, Malawi. 2University of North
Carolina, Department of Medicine, Chapel Hill, United States.
3
University of North Carolina, Department of Health Policy and
Management, Chapel Hill, United States. 4Lighthouse Trust, Lilongwe,
Malawi. 5University of North Carolina, Department of Epidemiology,
Chapel Hill, United States
Presenting author email: sarah_rutstein@med.unc.edu
Background: Multiple sexual partnerships, specifically concurrent
partnerships, may play an important role in HIV transmission. Persons
seeking HIV testing and counseling at sexually transmitted infection
(STI) clinics may exhibit riskier behavior than those seeking testing at
HIV Testing and Counseling (HTC) centers. We examined concurrency
and other risk behaviors among HIV-uninfected STI patients and HIVinfected and HIV-uninfected HTC patients in Lilongwe, Malawi.
Methods: We recruited participants from a central hospital STI clinic
(STI) and a nearby HTC Center (HTC) in Lilongwe, Malawi.
Participants provided demographics and sexual behavior. Summary
statistics were compared using independent group t-tests (continuous variables) and Pearson’s x2 tests (categorical variables). We
investigated associations between several demographic variables
with concurrent partnerships using logistic regression.
Results: HIV prevalence at HTC was 19.9% CI [0.172, 0.227]. HIVinfected and HIV-uninfected persons at HTC were more alike than
HIV-uninfected persons at STI. Among persons at HTC, HIV-infected
and HIV-uninfected differed in age, gender, and marital status but
there were no differences in risk behaviors. Condom use at last sex
was similar across all groups (p 0.60). HIV-uninfected persons at STI
had more sexual partners and were more likely to report concurrent
partnerships than either HTC group. Concurrent partnerships were
rare among women in either setting (n 3) so logistic regression
models were restricted to males (n 522). HIV-infected and HIVuninfected men testing in HTC were significantly less likely to report
concurrency than men at STI (OR0.13, CI[0.04, 0.46], OR0.29, CI[0.15,
0.55], respectively), holding age, marital status, and above-listed risk
behaviors constant.
Conclusion: Persons enrolled in the STI setting had a much higher
prevalence of concurrency than HIV-infected or HIV-uninfected
persons at HTC. Behavioral similarities and high HIV prevalence at
HTC may suggest important role that sexual networks play in
HIV acquisition risk. Even in a generalized epidemic, behavioral
84
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Average age
Track C Epidemiology and Prevention Science
STI (HIV-uninfected)
(n200)
HTC (HIV-infected)
(n 167)
28.4
32.2
HTC (HIV-uninfected)
(n 669)
Overall
p-value
29.9
B0.01
Male (%)
128 (64)
66 (39)
362 (54)
B0.01
Married (%)
132 (66)
107 (64)
349 (52)
B0.01
# Sexual Partners, last 4 weeks, mean (median)
1.2 (1)
0.92 (1)
0.84 (1)
B0.01
# Sexual Partners, last 3 months, mean (median)
1.4 (1)
1.0 (1)
0.92 (1)
B0.01
Exchanged sex for money (%)
32 (16)
4 (3)
18 (3)
B0.01
Concurrent partnerships, last 3 months (%)
Condom use at last sex (%)
41 (21)
26 (13)
5 (3)
20 (13)
34 (5)
98 (15)
B0.01
P0.60
6 (3)
9 (5)
37 (6)
P0.33
Sex with known HIV, last 3 months (%)
Demographics and HIV Risk Behaviors by Group.
interventions in STI and HTC clinics represent promising opportunities to reduce HIV acquisition.
THAC0202
Patients in routine HIV clinical care at-risk for potentially
transmitting HIV in the ‘test-and-treat’ era of HIV
prevention
Figure 1. A. Odds of Being At-Risk for Potentially Transmitting HIV,
B. Odds of Inadequate Adherence.
H. Crane1, M. Mimiaga2, B. Feldman1, R. Fredericksen1,
M. Mugavero3, J. Willig3, S. Safren4, W. Matthews5,
K. Christopoulos6, S. Boswell7, M. Kitahata8, M. Saag3,
K. Mayer7 and Centers for AIDS Research Network
of Integrated Clinical Systems (CNICS)
1
University of Washington, Seattle, Medicine, United States. 2The
Fenway Institute and Harvard Medical School, Boston, United States.
3
University of Alabama at Birmingham School of Medicine,
Birmingham, United States. 4Harvard Medical School, Boston, United
States. 5University of California-San Diego (UCSD), San Diego,
United States. 6University of California-San Francisco, San Francisco,
United States. 7Fenway Institute, Boston, United States. 8University
of Washington, Seattle, United States
Presenting author email: hcrane@uw.edu
Background: While test-and-treat policies with earlier initiation of
therapy can decrease HIV transmission, many patients are still at-risk
for transmitting HIV even after diagnosis and initiation of care.
This study examines rates and predictors of detectable viremia and
HIV transmission risk behaviors among patients in clinical care
and compares these to predictors of inadequate antiretroviral
adherence.
Methods: CNICS patients complete a touch-screen-based assessment
including drug/alcohol/tobacco use, adherence, and sexual risk
behavior measures. Data from 5 sites (Seattle, Boston, Birmingham,
San Diego, San Francisco) were included. We used generalized
estimating equations adjusting for age, race, sex, and site. Our
primary outcome, being at-risk for potentially transmitting HIV, was
defined as being sexually active with incomplete/no condom use in
the prior 6 months and having a detectable viral load.
Results: 15,140 assessments were completed by 5,905 patients.
Rates of detectable viremia with incomplete/no condom use were
1536% by site. Patients 50 years of age and women were less
likely to be at-risk than younger patients or men (p values B0.001).
At-risk patients were more likely to have ]2 sex partners in the
prior 6 months (54% vs. 19% p B0.001). In separate adjusted
analyses, patients reporting current amphetamine use or injection
drug use of any kind had more than double the odds of being at-risk
for potentially transmitting HIV (Figure). Patients reporting current
alcohol, marijuana, or cocaine/crack abuse had 1.5 times the odds
of being at-risk. Similar patterns of predictors were found for
inadequate adherence (Figure).
Conclusion: Even patients who have established outpatient HIV care
may engage in risky sexual behavior with detectable viremia, and
substance use, particularly amphetamines, may be one important
factor. Test-and-treat policies do not eliminate the need to focus on
prevention of potential HIV transmission risk with diagnosed patients
in care.
85
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
FRLBC04
BCG vaccination at birth induces non-specific CD4
T cell activation in HIV-exposed South African infants,
which may increase HIV transmission through
breastfeeding
A.K. Hesseling1, J.-A.S. Passmore2, H. Gamieldien2, C.E. Jones3,
W. Hanekom4, D.L. Sodora5 and H.B. Jaspan2,5
1
Stellenbosch University, Desmond Tutu TB Centre, Cape Town,
South Africa. 2University of Cape Town, Institute of Infectious
Diseases and Molecular Medicine, Clinical Lab Sciences, Cape Town,
South Africa. 3Imperial College London, Academic Department of
Pediatrics, London, United Kingdom. 4University of Cape Town,
Institute of Infectious Diseases and Molecular Medicine, South
African TB Vaccine Institute, Cape Town, South Africa. 5Seattle
Biomedical Research Institute, Seattle, United States
Presenting author email: hbjaspan@gmail.com
Background: In sub-Saharan Africa, where BCG vaccine is routinely
given around birth to protect from disseminated TB, almost a third
of infants are HIV-exposed. HIV preferentially infects activated
CCR5CD4 cells. Highly HIV-exposed, seronegative individuals
have relatively decreased peripheral CD4 T cell activation. We
hypothesized that routine BCG vaccination of HIV-exposed neonates
causes non-specific CD4T cell activation.
Methods: HIV-exposed, uninfected South African infants were
randomized to receive either BCG at birth or at 8 weeks of age,
and blood was collected at birth, 2 and 6 weeks. Unstimulated
PBMCs were stained with viability dye, anti-CD3, -CD4, -CD8, -CCR5,
the activation markers CD38 and HLA-DR, and the proliferation
marker Ki67. PBMC and plasma cytokine mRNA and protein levels
were measured using RTPCR and Luminex respectively.
Results: At 6 weeks of age, there was a significantly higher HLA-DR
expression and CCR5, HLA-DR and CD38 co-expression on CD4 T
cells (p .02 and p.01 respectively; n94) in the infants who had
received BCG at birth compared to unvaccinated infants (delayed
arm). In contrast, there was no difference in CD8 T cell activation
between BCG-vaccinated and unvaccinated infants. The CCR5
agonist, MIP1b, was significantly higher at 6 weeks in plasma of
unvaccinated infants (p .02). There were no differences in plasma
IFN-a, IFN-g, MCP-1, TNF-a, IL-8, GMCSF or IP-10 levels, nor
differences in PBMC IFN-a, IFN-g, RANTES, TNF-a, IL-8, IL-10, TGFb, OAS or IP-10 mRNA levels, between vaccinated and unvaccinated
infants.
Conclusion: BCG vaccination induces non-specific CD4 T cell
activation and down-regulation of MIP-1b expression. This elevated
T cell activation may increase HIV infections in breastfed infants and
may contribute to rapid disease progression. Further research
regarding the risks and benefits of BCG vaccination in HIV-exposed
infants is needed to inform policy and practice.
FRLBX05
Continuum of HIV care: differences in care and treatment by
sex and race/ethnicity in the United States
H.I. Hall1, E.L. Frazier1, P. Rhodes1, D.R. Holtgrave2, C. FurlowParmley1, T. Tang3, K.M. Gray1, S.M. Cohen1 and J. Skarbinski1
1
Centers for Disease Control and Prevention, Atlanta, United States.
2
Johns Hopkins Bloomberg School of Public Health, Baltimore, United
States. 3ICF International, Atlanta, United States
Presenting author email: ixh1@cdc.gov
Background: Early diagnosis of HIV, prompt linkage and sustained
care, and antiretroviral therapy are associated with reduced
Figure 1. Percentage of persons with HIV engaged in selected
stages of the continuum of care, by sexUnited States.
Figure 2. Percentage of persons with HIV engaged in selected
stages of the continuum of care, by race/ethnicity-United States.
individual morbidity and mortality and onward transmission of the
virus. However, optimal levels of these indicators may not be
achieved by all population groups with HIV.
Methods: Using data from CDC’s National HIV Surveillance System,
we determined the number of persons living with HIV aware and
unaware of their infection using back-calculation models, and the
percentage of persons linked to care within three months of
diagnosis based on CD4 and viral load tests. We estimated the
percentages of persons retained in care, prescribed antiretroviral
therapy, and with viral suppression using data from the Medical
Monitoring Project, a surveillance system of persons in HIV care in
select areas representative of all such persons in the United States.
Using these data, we determined the continuum of care indicators
for persons with HIV by sex and race/ethnicity.
Results: Of the estimated 1,148,200 persons living with HIV in 2009
in the United States, 869,000 (76%) were male, 510,600 (44%) black
or African American, and 220,400 (19%) Hispanic or Latino. The
percentages of females diagnosed, linked to care, retained in care,
and prescribed ART were slightly higher than for males but there
were no substantial differences in viral suppression. The percentages
were lower in each stage of the continuum for blacks/African
Americans and Hispanics/Latinos compared with whites. Overall,
857,276 persons with HIV were not virally suppressed, including
75% of males, 79% of blacks/ African Americans, 74% of Hispanics/
Latinos, and 70% of whites. Numbers were too small to present for
other races.
Conclusion: Disparities exist in each step of the continuum
for blacks/African Americans and Hispanics/Latinos. Additional
efforts are needed to ensure that all persons with HIV get
optimal care, reduce disparities, and ultimately reduce HIV
transmission.
86
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
TUPDC0201
One in ten couples in Mozambique is serodiscordant and
most do not know it: results from the 2009 national HIV
seroprevalence survey
J.D. Fishel1, S.E. Bradley1, P.W. Young2, F. Mbofana3 and C. Botao3
1
ICF International, Calverton, United States. 2CDC-Mozambique,
Maputo, Mozambique. 3National Institute of Health, Maputo,
Mozambique
Background: Serodiscordant couples are an important source of
new HIV infections. This analysis explores the prevalence of HIV
serodiscordance among couples, HIV-testing behavior, and factors
associated with serodiscordance in Mozambique.
Methods: A nationally representative HIV seroprevalence survey was
conducted in Mozambique in 2009. Couples who were married or
cohabiting were identified, their HIV status compared, and factors
associated with concordant positivity versus serodiscordance were
measured. Data were analyzed using cross-tabulation and logistic
regression.
Results: 15% of 2,468 couples in Mozambique had one or both
members HIV infected. Serodiscordant couples outnumbered concordant positive couples two to one (10.2% vs. 4.9%). Among
discordant couples, only 15% reported that both members of the
couple had been tested for HIV and received the results. Overall,
6% of discordant couples used a condom the last time they had sex
with each other (compared with 3% of all couples). Condom use was
positively associated with exposure to HIV testing and with HIVseropositivity in the female partner. The only consistent risk factor
for couples being concordant positive vs. discordant in the multivariate analysis was a history of self-reported symptoms of sexually
transmitted infections (STIs). For example, in the binomial model, if
either member of the couple had an STI, the couple was less likely to
be discordant vs. concordant positive (adjusted odds ratio 0.40; 95%
confidence interval 0.18, 0.89).
Conclusion: One in every ten couples in Mozambique is HIVserodiscordant. The HIV-negative partners in this group are at high
risk for becoming infected; however, few discordant couples know
that they are discordant, and are therefore unlikely to take protective
measures.
C7 - Epidemiology of HIV in the general
population, women, adolescents and
children
FRLBX01
HIV prevalence trends after scale-up of antiretroviral
treatment: a population-based study in a poor rural
community in KwaZulu-Natal
J. Zaidi1, E. Grapsa1, F. Tanser1, M.-L. Newell1,2 and T. Bärnighausen1,3
1
Africa Centre for Health and Population Studies, University of
KwaZulu-Natal, Mtubatuba, South Africa. 2MRC Centre for
Epidemiology of Child Health, University College London Institute of
Child Health, London, United Kingdom. 3Harvard School of Public
Health, Global Health and Population, Boston, United States
Presenting author email: jaffer_mz@hotmail.com
Background: Unless compensated by large declines in HIV incidence,
the survival benefits of antiretroviral treatment (ART) are expected
to lead to increases in HIV prevalence, especially in the world regions
with already very high prevalence rates. We investigate HIV
Figure 1.
Female prevalence trends by age group.
Figure 2.
Male prevalence trends by age group.
prevalence trends in one such region, a rural in KwaZulu-Natal,
South Africa, before and after the scale-up of antiretroviral treatment (ART), over the period 20042011.
Methods: We estimated adult HIV prevalence trends (overall and in
sex-age strata), using data from the longitudinal, population-based
HIV surveillance at the Africa Centre for Health and Population
Studies. To control for selective surveillance non-participation on a
wide range of observed, demographic, social, economic and
behavioral factors, we use multiple imputation with chained
equations (MICE).
Year/
Method
Crude Prevalence
Estimates (%)
2004
2005
2006
2007
2008
2009
2010
2011
20.0
20.3
20.0
22.1
22.8
26.5
28.9
27.8
(18.421.6)
(19.721.0)
(19.320.7)
(21.322.8)
(22.123.5)
(25.727.3)
(28.129.7)
(26.629.0)
Imputed Prevalence
Estimates (%)
21.9
20.6
20.2
22.2
23.4
27.0
28.3
28.8
(21.122.7)
(19.721.5)
(19.021.4)
(20.723.6)
(22.224.5)
(26.028.0)
(27.029.6)
(27.430.3)
Overall prevalence estimates by method and year.
87
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Results: We find a clear upward trend in both crude an imputed
prevalence estimates for the overall population, which was particularly large in 2010 and 2011, i.e., at a time when ART coverage under
the current South African ART guidelines had reached high levels
(about 75% in 2010). For women aged 2549, we found a clear
increase in HIV prevalence starting in 2006, but we did not find
similar time trends in women aged 1524, or men.
Conclusion: We find a large increase in overall adult HIV prevalence
in a community in rural KwaZulu-Natal with traditionally very high
HIV prevalence and recent achievements of high ART coverage.
Decomposing the HIV trends by sex and age group, we find that the
increase in overall adult HIV prevalence is largely driven by increases
in women aged 2549, i.e., the sex-age group with the largest
absolute number of people receiving ART. These results suggest that
the increase in overall HIV prevalence is due to increased survival of
HIV-infected people following the ART scale-up, rather than due to
dramatic increases in HIV incidence.
Track C Epidemiology and Prevention Science
Figure 2.
HIV prevalence in Urban vs Rural Populations.
Figure 3.
Estimated weight of major cities.
MOPDC0202
The urban HIV epidemic in eastern and southern Africa:
need for better KYE/KYR to inform adequate city responses
H. Van Renterghem1, M. Colvin2, I. de Beer3, J. Gunthorp4, M. Odiit1,
L. Thomas5, H. Jackson6 and M. Getahun7
1
UNAIDS, Windhoek, Namibia. 2Maromi Health Research, Cape Town,
South Africa. 3PharmAccess Foundation, Windhoek, Namibia.
4
Southern African AIDS TRUST, Johannesburg, South Africa. 5Wits
University, Johannesburg, South Africa. 6UNAIDS, Johannesburg,
South Africa. 7UNDP, Johannesburg, South Africa
Presenting author email: vanrenterghemh@unaids.org
Background: HIV prevalence tends to be higher in urban areas and
this trend will be exacerbated by continuing urbanization and the
anticipated growth of slums. This concentration of HIV in cities
requires a matched response that is informed by evidence and
adequately resourced. To date, little research or emphasis has been
put on urban responses to the epidemic.
Methods: An assessment of the status of urban HIV epidemics
and responses in Eastern and Southern Africa (ESA) was based on
a synthesis of epidemiological data and literature, evaluation of
existing city responses, expert consultations through SEARCH-network and the results from 2 recent city KYE/KYR pilot exercises in
Durban and Windhoek.
Results: The review shows that (i) city epidemics show important
intra-city variations with higher prevalence in slum-dwellers, women
and key populations (ii) that large cities with generalised epidemics
host epidemics that are comparable in size to many national
epidemics; (iii) in most ESA countries 3070% of national epidemics
is concentrated in the top 46 cities; (iv) epidemiological trends and
modes of transmission are poorly understood; (v) City prevention
responses are sparse, not comprehensive, poorly coordinated, not
evidence-based and underfunded; (vi) HIV treatment is increasingly
becoming available but universal access is rare; (vii) City specific KYE/
KYR exercises provide clear information on gaps and can empower
city leadership to strengthen coordination and planning.
Conclusion: The urban HIV epidemic in ESA is large and expected to
increase over the next decade. However city epidemics are poorly
understood and city specific responses are inadequate. For large and
generalized city epidemics, it is recommended that city specific KYE/
KYR and synthesis exercises be conducted. It is recommended that
sampling frameworks of epidemiological surveys be designed to be
representative of urban areas. Ownership by city authorities and
partnership with health & social services and civil society is crucial.
C8 - Epidemiology of HIV in people who
use drugs
MOAC0401
Figure 1.
Ranking of Urban HIV Epidemics (ESA).
Low risk of HIV and STI among drug users in Amsterdam
88
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
partner (aOR 4.09, 95% CI 1.5910.53) was associated with
unprotected sex. HIV-infected participants were less likely to report
unprotected sex (aOR 0.07, 95% CI 0.020.37).
Conclusion: HIV incidence declined from 1986 onwards, accompanied
by decreasing injection risk behaviour. STI prevalence is low and
unprotected sex is mainly attributable to sex with a steady partner
and less common in HIV-infected participants. These findings strongly
suggest that DU are no longer at increased risk for HIV and STI, and do
not play a significant role in the current spread of HIV in Amsterdam.
MOAC0405
Figure 1. Observed and fitted HIV incidence in the Amsterdam.
B.P.X. Grady1, N. van der Knaap2, M. Schim van der Loeff1,
T. Heijman1, A. Speksnijder3, R. Geskus4 and M. Prins1,5
1
Public Health Service Amsterdam, Infectious Diseases, Research,
Amsterdam, Netherlands. 2University of Amsterdam, Amsterdam,
Netherlands. 3Public Health Service Amsterdam, Laboratory of Public
Health, Amsterdam, Netherlands. 4Public Health Service
Amsterdam, Laboratory of Public Health, Amsterdam, Netherlands.
5
Academic Medical Center (AMC), Internal Medicine, Infectious
Diseases, Tropical Medicine and AIDS, Amsterdam, Netherlands
Presenting author email: bgrady@ggd.amsterdam.nl
Background: To examine whether drug users (DU) of the Amsterdam
Cohort Study (ACS) are still at risk for HIV and STI we studied trends
in HIV incidence rates and risk behaviour from 19852010. STI
prevalence and determinants of unprotected sex were studied
among participants with a recent visit in 20102011.
Methods: The ACS is an open, prospective cohort study on HIV.
Trends in HIV incidence over calendar time were modelled using
Poisson regression. Trends in risk behaviour were modelled via
logistic regression, using generalized estimating equations to correct
for multiple outcomes per individual. In 2010 an STI screening
(chlamydia, gonorrhoea and syphilis) was performed among 200
participants. Determinants of unprotected sex were studied using
logistic regression analysis. Generalized estimating equations were
used to account for multiple partner types per individual.
Results: The HIV incidence among 1657 participants of the ACS with
a total follow-up of 12,798 person-years (PY) declined from 5.96/100
PY (95% Confidence Interval (CI) 3.2111.05) in 1986 to less than 1/
100 PY from 1997 onwards. Both injection and sexual risk behaviour
declined over time, although the prevalence of unprotected sex
remained 31% in 2010. Out of 200 participants screened for STI in
20102011, median age 49 years (IQR 4359), only 5 (2.5%) were
diagnosed with an STI. In multivariable analysis, having a steady
Methamphetamine use is associated with sexual abuse and
HIV sexual risk behaviours among patrons of alcohol serving
venues in Cape Town, South Africa
C.S. Meade1, M.H. Watt2, K.J. Sikkema3, L.X. Deng4, K.W. Ranby4,
D. Skinner5, D. Pieterse5 and S.C. Kalichman6
1
Duke University School of Medicine, Psychiatry & Behavioral
Sciences, Durham, United States. 2Duke Global Health Institute,
Durham, United States. 3Duke University, Psychology &
Neuroscience, Durham, United States. 4Duke University, Durham,
United States. 5Stellenbosch University, Cape Town, South Africa.
6
University of Connecticut, Storrs, United States
Presenting author email: christina.meade@duke.edu
Background: South Africa’s Western Cape has experienced a
dramatic increase in methamphetamine (‘‘meth’’) use over the past
decade. There is concern that meth may further fuel the HIV
epidemic in this country because of its association with risky sexual
behavior. The present study describes the prevalence of meth use
and its association with HIV sexual risk behavior.
Methods: Adult patrons (N 3,328) in 12 alcohol-serving venues in a
mixed race township in Cape Town completed brief surveys that
assessed substance use, interpersonal violence, and sexual risk
behavior. Logistic regression models were used to test the relationship between meth use and HIV risk factors. Mediation models
examined pathways from childhood sexual abuse to meth use to HIV
risk behaviors.
Results: Meth use in the past 4 months was more common among
Coloured than Black persons (10.5% vs. 3.5%, pB.001). Meth use
was related to a history of childhood sexual abuse and recent sexual
assault (all p B.001). Among both men and women, meth users were
more likely than non-users to have had multiple sex partners,
engaged in sex trade, and been diagnosed with a sexually
transmitted infection (STI) in the past 4 months (all pB.01).
Meth was also associated with unprotected intercourse among
women and HIV diagnosis among men (all pB.01). Support was
found for a structural equation model in which meth use mediated
significant relations between childhood sex abuse and five sex risk
Women
Meth
No Meth
(n95)
(n1,360)
Men
Meth
No Meth
AOR
95% CI
(n117)
(n1,756)
AOR
95% CI
1.182.71
Multiple partners
28.4%
18.9%
2.42**
1.464.01
56.4%
44.2%
1.79**
Unprotected sex
66.3%
42.6%
2.45**
1.563.84
60.0%
48.0%
1.45
0.982.17
‘‘Sold’’ sex
‘‘Bought’’ sex
16.8%
6.3%
4.2%
2.4%
6.34**
3.45**
3.2612.35
1.319.06
31.6%
28.2%
8.1%
8.7%
4.64***
4.80***
2.967.27
3.037.61
Sexually transmitted infection
11.6%
4.4%
3.84***
1.848.02
15.55%
5.9%
2.95***
1.665.36
8.2%
8.3%
1.33
0.553.23
15.2%
6.1%
3.79***
1.957.36
HIV diagnosis (lifetime)
Associations between meth use and HIV sexual risk.
89
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
with high school or higher education (OR2.27; 95% CI1.343.86);
self-identification as sex worker (OR2.29; 95% CI1.393.77); and selfidentification as bisexual or heterosexual (OR2.77; 95% CI1.345.75).
Conclusion: Tailored strategies to reduce risky sex behavior associated with drug consumption are urgently needed among MSM in
Peru and must target subpopulations at the highest risks.
THAC0403
Predictors of dropping out of methadone maintenance
treatment in China: a six-year cohort study
X. Cao, Z. Wu, K. Rou and L. Pang
National Center for AIDS/STD Control and Prevention, Chinese
Center for Disease Control and Prevention, Division of Health
Eduction and Behavioral Intervention, Beijing, China
Presenting author email: xiaobincao@hotmail.com
Figure 1. Mediation model depicting mediated effects of childhood sexual abuse on multiple sexual risk behaviours through meth
[Mediation model].
behaviors; sold sex, bought sex, STI, unprotected sex, and multiple
partners were significantly predicted (R2 .21, .12, .08, .04, .02,
respectively).
Conclusion: Meth users are at increased risk for HIV transmission due to high risk sexual behaviors and being in violent
relationships. There is an urgent need to provide targeted HIV
prevention and substance abuse treatment to meth users living in
Cape Town.
THAC0305
Concurrent drug use and sexual risk behaviour among men
who have sex with men (MSM) in Peru
J. Peinado1, J.R. Lama1, P. Gonzales1, R. Cabello2, G. Sal y Rosas1 and
J. Sanchez1
1
Asociacion Civil Impacta Salud y Educacion, Lima, Peru. 2Asociacion
Via Libre, Lima, Peru
Presenting author email: jrlama@impactaperu.org
Background: Understanding concurrent drug consumption and
unprotected anal intercourse (UAI) behavior among MSM, would
contribute to develop tailored interventions for HIV prevention.
Methods: A HIV Sentinel Surveillance was conducted in five cities
of Peru in JuneOctober 2011. In this survey, MSM with high-risk
behavior who were unaware of their HIV serostatus, participated for
the assessment of HIV and syphilis status, and demographics and
sexual behavior patterns using computer-assisted self-interview. We
report socio demographics, sexual risk behaviors, and other characteristics for not using a condom during anal sex associated drug
consumption. A multinomial adjusted logistic regression analysis was
conducted to assess potential associations between concurrent drug
consumption and UAI behavior with other factors.
Results: Among 5,575 participants, 800 (14.3%) reported concurrent
drug consumption and UAI behavior in the last three months. Of
them, 43.3% were B 25 year-old and 86.6% had high school or a
higher education level. This behavior was independently associated
Background: China initiated Methadone Maintenance Treatment
(MMT) program in 2004, serving more than 343,000 clients by 2011.
High dropout rate was one of the special challenges that needed to
be addressed urgently. The aim of this study is to assess MMT clients’
dropout rate and to identify factors associated with dropout over the
six-year period.
Methods: A prospective cohort study was conducted in eight MMT
clinics of China from March 2004 to June 2010, involving 1511 drug
users who were enrolled in MMT program in 2004. Dropout and its
predictors were examined using Chi-square tests and Cox Proportional Hazards regression models.
Results: Over the six-year follow-up period, 972 (64.3%) clients
dropped out of treatment and clients were more likely to leave
treatment within 1.5 years after enrollment. The leading cause of
dropout was being arrested (48.7%), followed by emigration/being
out of town for work (10.5%) and self-withdrawn (10.3%). Adjusting
Hazard Ratio (HR) indicated that clients with high daily dose
( 60mg) (PB0.0001, HR0.38, 95% Confidence Interval (CI):
0.290.51), having relatives receiving MMT (P0.027, HR 0.72,
95% CI:0.540.96), and higher urine morphine positive result
(PB0.001, HR 0.63, 95% CI:0.520.76) were less likely to drop
out, whereas clients with needles sharing behaviors, and frequent
contact with current drug users had higher risk of dropout over the
six-year period (P B 0.05).
Conclusion: Specific interventions to decrease dropout are needed
to focus on clients with lower daily dose, sharing needles with
others and more frequent contact with current drug users.
The preventive role of family support on dropout should be
emphasized.
C9 - Epidemiology of HIV in male and
female sex workers
THAC0501
High and disproportionate burden of HIV among female sex
workers in low- and middle-income countries: a systematic
review and meta-analysis
S. Baral1, C. Beyrer1, K. Muessig2, T. Poteat1, A. Wirtz1, M. Decker3,
S. Sherman4 and D. Kerrigan5
1
Center for Public Health and Human Rights, JHSPH, Epidemiology,
Baltimore, United States. 2Johns Hopkins School of Public Health,
International Health, Baltimore, United States. 3Johns Hopkins
90
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Figure 1.
Track C Epidemiology and Prevention Science
SW Meta-Analysis.
Bloomberg School of Public Health, Population, Family, and
Reproductive Health, Baltimore, United States. 4Johns Hopkins
Bloomberg School of Public Health, Epidemiology, Baltimore,
United States. 5Johns Hopkins Bloomberg School of Public Health,
Health, Behavior, and Society, Baltimore, United States
Presenting author email: sbaral@jhsph.edu
Background: Female sex workers (FSW) have long been known to be
a most-at-risk population (MARP) for HIV secondary to biological,
behavioral, and structural risk factors. However, three decades into
the HIV pandemic, there remains a limited understanding of the
burden of HIV among these women.
Methods: This study included a systematic review of HIV prevalence
data among FSW from low and middle income countries published
between January 1st, 2007, and June 25, 2011. In addition, metaanalyses were completed using the Mantel-Haenzel method with a
random-effects model characterizing an odds ratio (OR) for the HIV
prevalence among FSW compared to that of all reproductive-age
women.
Results: Data from 102 studies representing 99,878 female sex
workers across 50 countries were included in the analyses. The
overall HIV prevalence was 11.8% (95% CI 11.612.0) with a pooled
OR for HIV infection of 14.1 (95% CI 10.519.0) with wide
intraregional ranges in the pooled HIV prevalence and OR for
HIV infection. In 25 countries with medium and high background
HIV prevalence, 32.0% (95% CI 31.032.1) of 27009 women
were HIVpositive and the OR for infection was 11.9 (95% CI
9.315.2).
Conclusion: These findings highlight that though there is a dearth of
data characterizing HIV risk among FSW, where studied, burden of
disease is disproportionately high. These data suggest an urgent need
to scale up access to quality HIV prevention programming including
considerations of the legal and policy environments in which sex
work operate, and the critical role of stigma, discrimination and
violence targeting FSW.
THPDE0201
Hyper-endemic HIV seroprevalence among young female
sex workers in post-conflict, northern Uganda: a call for
social and structural HIV interventions
K. Shannon1, M. Akello2, K. Muldoon3, A. Simo3 and G. Muzaaya2
1
British Columbia Centre for Excellence in HIV/AIDS University of
British ColumbiaSchool of Population and Public Health, Faculty of
Medicine, Vancouver, Canada. 2The AIDS Support Organisation-TASO
Uganda, Gulu, Uganda. 3BC Centre for Excellence in HIV/
AIDSUniversity of British Columbia, Vancouver, Canada
Presenting author email: kshannon@cfenet.ubc.ca
91
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Background: Despite substantial data globally suggesting expansion
of sex work markets in settings with recent political, economic and
social transitions, there exists almost no data on HIV prevalence
among SWs in post-conflict settings, particularly in sub-Saharan
Africa. Of further concern, given increasing efforts to criminalize HIV
and sex work in much of sub-Saharan Africa, there remains an
important need to understand the HIV prevention and treatment
needs of sex workers.
Methods: In 2011, 400 young women SWs ( 14 years of age)
completed baseline interview-administered questionnaires and confidential HIV testing. SWs were recruited through extensive peer
outreach (current/former SWs), ethnographic mapping and timelocation sampling to street and indoor sex venues. Bivariate and
multivariate analyses were conducted to examine associations with
HIV seropositivity.
Results: Of a total of 400 young women SWs, the median age was 21
years (IQR1526). The HIV seroprevalence was 34% (136), of whom
59% (80) were new HIV seroinfections, and 32% ( 44) were on ART. The
majority (96%) solicited clients in bars, 41% (165) in lodges, and 35%
(183) along truck stop. A high number (56%, 222) of SWs reported
difficulty accessing condoms in the last 6months. HIV seropostivity was
associated in bivariate analysis with supporting dependent children
(OR 3.30, 1.576.89). In multivariate analyses, HIV seropositivity
was associated with older age (AOR 1.18, 95% CI1.101.26), lower
sex work income (AOR0.99, 0.990.99) and reduced likelihood of
having a ‘sugar daddy’ (AOR 0.49, 0.250.99).
Conclusion: Young women SWs are experiencing an alarming rate of
HIV infection in Northern Uganda, with more than half unaware of
their HIV seropositivity status. These data suggest critical gaps in HIV
prevention, treatment and care services and an urgent need for
social and structural HIV interventions that support and reach
isolated young women SWs, including reducing stigma, policy reform,
and peer-led outreach initiatives.
C10 - Epidemiology of HIV in men having
sex with men (MSM)
Track C Epidemiology and Prevention Science
Figure 1.
Simulation results.
patterns of sexual partnering, UAI, and levels of virologic suppression
among MSM in Atlanta to estimate how frequently black and white
HIV-negative MSM would have UAI with a sex partner with
transmission potential (viral load500 copies/ml).
Results: Among 556 MSM recruited to-date, the 12-month median
number of UAI partners was 2 for both black and white men
(p 0.19). Based upon HIV prevalence, viral-load estimates and
reported partnership characteristics, the estimated average annual
probabilities (95% CI) of having1 UAI partner with transmission
potential were 0.37 (0.32, 0.43) for black and 0.20 (0.15, 0.24) for
white MSM (pB.0001). The estimated number of UAI partners to
have a 50% chance of having a UAI partner with viral load500
copies/ml was 3 for black and 7 for white MSM.
Conclusion: HIV-negative black MSM have comparable risk behaviors, but have a substantially higher likelihood of encountering a UAI
partner with viral load 500 copies/ml. Our results suggest a limited
ability of behavioral interventions to eliminate racial disparities, and
support the need to increase HIV testing with linkage to care and
antiretroviral treatment of all HIV-positive MSM to reduce the risk of
HIV transmission from sex partners.
MOAC0101
MOAC0103
Equal behaviors, unequal risks: the role of partner
transmission potential in racial HIV disparities among men
who have sex with men (MSM) in the US
Foreign location of birth and time since immigration are
associated with HIV status among Latino MSM in the United
States
E. Rosenberg1, C. Kelley2, B. O’Hara1, P. Frew2, J. Peterson3,
T. Sanchez1, C. del Rio4 and P. Sullivan1
1
Emory University Rollins School of Public Health, Epidemiology,
Atlanta, United States. 2Emory University School of Medicine,
Infectious Diseases, Atlanta, United States. 3Georgia State University,
Psychology, Atlanta, United States. 4Emory University Rollins School
of Public Health, Global Health, Atlanta, United States
Presenting author email: esrose2@emory.edu
A. Oster1, K. Russell1, R. Wiegand1, B. Le1, E. Valverde1, D. Forrest2,
M. Cribbin1, G. Paz-Bailey1 and NHBS Study Group
1
Centers for Disease Control and Prevention, Division of HIV/AIDS
Prevention, Atlanta, United States. 2University of Miami, Miami,
United States
Presenting author email: aoster@cdc.gov
Background: Differences in individual risk behavior do not explain
the large disparities in HIV prevalence and incidence between black
and white MSM in the US. Patterns of partner selection, virologic
suppression in HIV-positive sex partners, and unprotected anal
intercourse (UAI) may jointly contribute to these disparities, but
are not well understood.
Methods: The Involvement study is an ongoing cohort of black and
white MSM in Atlanta designed to evaluate individual, dyadic, and
community level factors that might explain HIV disparities. Participants are recruited from community-based venues, tested for HIV,
and surveyed. We used Monte Carlo simulation with data about
Background: In the United States, Latino men who have sex
with men (MSM) are disproportionately affected by HIV. However,
little is understood about variations in HIV risk by location of birth
and time since immigration for foreign-born MSM. We assessed
differences in HIV prevalence among Latino MSM by these
characteristics.
Methods: For the National HIV Behavioral Surveillance System
(NHBS) among MSM, venue-based sampling was used to recruit
men. In 20 cities in the continental United States, men were
interviewed and tested for HIV infection. We analyzed data for Latino
men who reported1 male sex partner in the past 12 months. We
compared HIV prevalence for three groups (U.S.-born, foreign-born
who immigrated 5y ago, and foreign-born who immigrated
92
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Table 1.
Track C Epidemiology and Prevention Science
Intervention effects on HIV STI incidence after 12 months, e positise or hid active STIs it enrollment Tijuana
% of sample
HIV prevalence
APR
95% CI
1.5 (per 10y increase)
1.31.6
Age (yrs)
1819
6%
2024
20%
9%
2529
19%
13%
3039
30%
22%
4049
20%
29%
6%
34%
0 to $ 19.999
35%
23%
1.8
1.12.9
$20,000 to $39,999
30%
19%
1.4
0.92.1
$40,000 to $74,999
23%
13%
1.0
0.71.4
$75,000 or more
11%
15%
Referent
Referent
U.S.-born
55%
16%
1.8
1.12.7
Foreign-born, immigratedB5 y ago
Fcreign-born, immigrated ]5 y ago
7%
37%
10%
23%
Referent
1.9
Referent
1.32.9
100%
19%
50
Annual household income
4%
Location of birth and time since immigration
Total
MSM: men who have sex with men; APR adjusted prevalence ratio; confidence intervel.
5y ago). We used generalized estimating equations (clustered on
city of interview) to identify factors associated with prevalent HIV
infection. We also determined the proportion unaware of their
infection (those who tested positive but reported a negative or
unknown HIV status during the interview).
Results: We interviewed and tested 1734 Latino MSM. HIV prevalence was highest among foreign-born MSM who immigrated 5y
ago (see table). Among HIV-positive Latino MSM, 43% were unaware
of their infection; this did not vary by location of birth or time since
immigration. In multivariate analysis including age and income, HIV
infection was more prevalent among foreign-born MSM who
immigrated 5y ago and U.S.-born Latino MSM, both compared
with persons who were foriegn-born and immigrated 5y ago. HIV
prevalence was also associated with increasing age and income B$20,000.
Conclusion: Lower HIV prevalence among foreign-born Latino MSM
shortly after immigration contrasts with higher HIV prevalence
among foreign-born Latino MSM 5 years after immigration and
suggests a critical window of opportunity for HIV prevention.
Prevention activities among Latino MSM should prioritize those with
low income, who are at particular risk for HIV infection.
understand this trend, we examined HIV prevalence and testing
during 19942008 among young men who have sex with men
(MSM).
Methods: The Young Men’s Survey (19941998, ages 1522y, and
19982000, ages 2329y) and the National HIV Behavioral Surveillance System (20042005 and 2008, ages 18y) conducted interviews and HIV testing among MSM recruited by venue-based
sampling. We analyzed data of MSM ages 1829y from Baltimore,
Los Angeles, Miami, New York City, and San Francisco. We used
logistic regression to assess if interview year was associated with HIV
prevalence and testing for MSM ages 1822y and 2329y, after
adjusting for city, race/ethnicity, and education (ages 2329y only).
We also calculated model-adjusted prevalence of HIV infection and
testing by year.
Results: Overall, HIV prevalence was 11% and 16% among MSM ages
18-22y and 2329y, respectively. Multivariable analysis demonstrated no change in HIV prevalence over time among MSM ages
1822y (p 0.6, Figure 1). However, there was an increase
MOAC0104
Trends in HIV prevalence and HIV testing among young
MSM: five United States cities, 19942008
A. Oster, C. Johnson, B. Le, T. Finlayson, A. Balaji, A. Lansky,
J. Mermin, L. Valleroy, D. MacKellar, S. Behel, G. Paz-Bailey and YMS
and NHBS Study Groups
Centers for Disease Control and Prevention, Division of HIV/AIDS
Prevention, Atlanta, United States
Presenting author email: aoster@cdc.gov
Background: During 20062009, HIV incidence surveillance estimated that new infections increased 34% among men ages
1329y who have sex with men in the United States. To better
Figure 1.
HIV prevalence among young MSM*.
93
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Figure 2.
Recent HIV testing among young MSM*.
in HIV prevalence among MSM ages 2329y of borderline significance (p 0.07). HIV testing increased substantially (p B0.0001 for
both age groups, Figure 2). However, the proportion (78%) of HIVinfected MSM previously unaware of their infection did not change
over time; among these, 47% had been tested in the past 12 months.
Conclusion: Among young MSM, high HIV prevalence and proportion
previously unaware of their infection are consistent with national
trends. Gains in HIV testing among young MSM are encouraging, but
stable proportions unaware of their infections suggest that more,
and perhaps more frequent, HIV testing is needed, consistent with
CDC guidelines. Getting more young MSM tested, aware of their
infection, and into appropriate care would help prevent ongoing
transmission.
Track C Epidemiology and Prevention Science
Methods: Between 7/09 and 10/10, BMSM were enrolled in 6 U.S.
cities to evaluate feasibility of a multi-component prevention
intervention. This analysis focuses on the correlates of being newly
diagnosed with HIV, including multivariable logistic regression. HIV
testing was performed at study sites; central confirmation of results
is underway.
Results: HPTN 061 enrolled 1553 BMSM, whose median age was 39;
43% self-identified as gay/homosexual, 41% bisexual, 3% transgender, 10% straight/heterosexual. Of 96% who agreed to be tested,
10% indicated they were previously HIV-infected (PHIV), while 12%
were newly diagnosed with HIV (NHIV). Compared to PHIV, NHIV
were younger less likely to use marijuana poppers stimulants or
inject drugs reported less internalized homophobia and lower levels
of religious affiliation NHIV were more likely to be diagnosed with
syphilis and anogenital gonorrhea/chlamydia than PHIV, and more
likely to be diagnosed with syphilis or anogenital chlamydia than HIVuninfected BMSM. Compared to HIV-uninfected BMSM, NHIV BMSM
were more likely to be older unemployed engage in unprotected anal
intercourse have multiple bacterial STDs, and were more likely to
come from cities other than San Francisco.
Conclusion: Structural, behavioral, and biological factors (e.g.
unemployment, unprotected anal sex, and STDs, but not increased
substance use) are associated with new infections among American
BMSM, who differ behaviorally from men who have previously been
diagnosed. Given the high rates of HIV infection among BMSM,
culturally-tailored programs that encourage repeated HIV/STD testing, engagement in care, and innovative prevention strategies
addressing current risks are urgently needed to decrease further
spread.
MOAC0106
MOAC0105
An evolving concentrated epidemic: comparison of
socioeconomic, behavioural and biological factors among
newly diagnosed, previously diagnosed and HIV-negative
black men who have sex with men in six US cities
(HPTN 061)
K. Mayer1, L. Wang2, B. Koblin3, C. Mao2, S. Mannheimer4,
M. Magnus5, C. del Rio6, S. Buchbinder7, L. Wilton8, V. Cummings9,
C. Watson5, S. Griffith10, D. Wheeler11 and HPTN 061 Protocol Team
1
The Fenway Institute/Harvard Medical School, Boston, United
States. 2Statistical Center for HIV/AIDS Research & Prevention
(SCHARP), Seattle, United States. 3New York Blood Center, New York,
United States. 4Harlem Hospital/Columbia University, Department of
Medicine/Mailman School of Public Health, New York, United States.
5
The George Washington University, Department of Epidemiology
and Biostatistics, Washington, United States. 6Emory University
Rollins School of Public Health, Department of Epidemiology, Atlanta,
United States. 7San Francisco Department of HealthHIV Research
Division, San Francisco, United States. 8Binghamton University,
Department of Human Development, Binghamton, United States.
9
Johns Hopkins University School of Medicine, Pathology
Department, Baltimore, United States. 10FHI 360, Durham,
United States. 11HPTN 061 Protocol Team, New York, United States
Presenting author email: kmayer@fenwayhealth.org
Background: Black MSM (BMSM) constituteB1% of the U.S. population, but25% of incident HIV infections. Enhanced understanding of
factors associated with new interventions can provide data to inform
programs needed to address this disproportionate epidemic.
Correlates of HIV incidence among black men who have sex
with men in 6 U.S. cities (HPTN 061)
B. Koblin1, K. Mayer2, S. Eshleman3, L. Wang4, S. Shoptaw5, C. del
Rio6, S. Buchbinder7, M. Magnus8, S. Mannheimer9,10, T.-Y. Liu4,
V. Cummings3, E. Piwowar-Manning3, S. Fields11, S. Griffith12,
V. Elharrar13, D. Wheeler14 and HPTN 061 Study Team
1
New York Blood Center, Laboratory of Infectious Disease Prevention,
New York, United States. 2Fenway Health and Beth Israel Deaconess
Hospital, Boston, United States. 3Johns Hopkins University School of
Medicine, Department of Pathology, Baltimore, United States. 4Fred
Hutchinson Cancer Research Center, Vaccine and Infectious Disease
Division, Seattle, United States. 5University of California, Los Angeles,
Department of Family Medicine, Los Angeles, United States. 6Emory
University Rollins School of Public Health, Department of Global
Health, Atlanta, United States. 7San Francisco Department of Public
Health, San Francisco, United States. 8George Washington University,
School of Public Health and Health Services, Department of
Epidemiology and Biostatistics, Washington DC, United States.
9
Harlem Hospital/ Columbia University, Department of Medicine,
New York, United States. 10Columbia University Mailman School of
Public Health, Department of Epidemiology, New York, United States.
11
Florida International University-College of Nursing and Health
Sciences, Miami. 12FHI 360, Research Triangle Park, United States.
13
NIAID, National Institutes of HealthClinical Prevention Research
Branch, Bethesda, United States. 14Loyola University
ChicagoGraduate School of Social Work, Chicago, United States
Presenting author email: bkoblin@nybloodcenter.org
Background: Black/ African American MSM (BMSM) in the United
States are affected by HIV at dramatically disproportionate rates
compared to MSM of other race/ethnicities. Current HIV incidence
94
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
estimates in this group are needed to appropriately target prevention efforts.
Methods: In 200910, HPTN 061 recruited BMSM in Atlanta, Boston,
Los Angeles, New York City, San Francisco and Washington D.C. for a
feasibility study of a multi-component intervention to reduce HIV
infection. Participants reporting ]1 episode of unprotected anal
intercourse with a man in the past six months were evaluated
at baseline, 6 and 12 months. HIV status at enrollment was
based on real-time testing performed at study sites and confirmatory
testing at the HPTN Network Laboratory. HIV incidence based on HIV
seroconversion was calculated as number of events/person-years.
Confidence intervals were calculated using exact methods.
Results: Of 1553 BMSM enrolled, 174 reported a prior HIV diagnosis
and 46 refused HIV testing or a specimen was not available at
baseline. Of those without a prior HIV diagnosis (n 1333), 1168
were HIV-uninfected, and 165 (12.4%) were newly diagnosed at
baseline (including 3 with acute HIV infection). Among the 1168 HIV
uninfected men at baseline, 26 acquired HIV infection during follow
up for a 2.8% annual HIV incidence rate (95% CI: 1.84.1%). HIV
incidence was higher among menB30 yrs (5.9%; 95% CI: 3.69.1%)
compared men30 yrs (1.0%; 95% CI: 0.42.2%), men identifying as
exclusively gay/homosexual (5.0%; 95% CI: 2.68.8%) compared to
bisexual (1.5%; 95% CI: 0.43.7%) and men reporting unprotected
receptive anal sex (4.9%; 95% CI: 3.07.4%) compared to those not
(1.0%; 95% CI: 0.32.4%).
Conclusion: In the largest cohort of prospectively-followed BMSM in
the US, HIV incidence was high, particularly among young and gayidentified BMSM. Targeted and tailored culturally appropriate
combination HIV prevention strategies incorporating behavioral,
social and biomedical based interventions are urgently needed to
lower these rates.
THAC0302
Men who have sex with men and the HIV epidemic
in Morocco: results from a respondent-driven sampling
study
O. Mellouk1,2, K. Alami3, H. El Rhilani3, N. Rafif1, A. Abadie1,
L. Ouarsas4, A. Bennani5, B. El Omari6, I. Oumzil7 and L. Johnston8
1
ALCS, Marrakech, Morocco. 2ITPC North Africa, Marrakech,
Morocco. 3UNAIDS Morocco, Rabat, Morocco. 4ALCS, Agadir,
Morocco. 5PNLS, Rabat, Morocco. 6Fonds Mondial, Rabat, Morocco.
7
INH, Rabat, Morocco. 8UNAIDS, Amsterdam, Netherlands
Presenting author email: o.mellouk@gmail.com
Background: HIV prevalence in the general population in Morocco
is below 1%. There is currently no reliable data documenting
HIV among men who have sex with men (MSM) in Morocco.
This population is hard to reach due to social stigma, discrimination
and the illegal status of male-to-male sex in Morocco.
From November 2010 to March 2011, two integrated behavioural
and biological surveillance (IBBS) surveys were conducted
(Marrakech, Agadir), among MSM in Marrakech and Agadir to
obtain measure HIV and syphlis prevalence and associated risk
behaviors.
Methods: Using Respondent-Driven Sampling (RDS), 669 MSM (346
in Marrakech and 323 in Agadir) were enrolled in the study.
Respondents were males aged 18 and above who reported to
have had anal sex with another male in the past six months.
Consenting MSM completed a behavioral questionnaire and were
tested for HIV and syphilis (venous blood). Weighted analysis was
performed with Respondent Driven Sampling Analysis Tool (RDSAT)
Version 6.0.
Track C Epidemiology and Prevention Science
Results: The median age of sexual debut for MSM was at 16 years.
HIV prevalence among MSM in Agadir was 5.6% and 2.8% in
Marrakech; prevalence of syphilis was 7.0% in Agadir and 10.8% in
Marrakech. Among MSM who tested positive for HIV, 31.6% in Agadir
and 56.4% in Marrakech were co-infected with syphilis. MSM
reported multiple types of sexual partners, including occasional
and commercial. Only 27.6% of MSM in Agadir and 17.4% of MSM in
Marrakech reported always using a condom with any male partner
during anal sex in the past six months.
Conclusion: MSM are at a high risk for HIV and other sexually
transmitted diseases. Current prevalence of HIV in MSM is
higher than the general population. These findings provide
appropriate evidence to support the focus on addressing HIV
among MSM in the National Strategic Plan 20122016 on HIV of
Morocco.
THAC0303
The recent impact of MSM on the prevalence of HIV-1
infection among young men in Thailand
R. Rangsin1, K. Kana2, T. Chuenchitra2, A. Sunantarod3, S. Meesiri2,
W. Areekul1 and K.E. Nelson4
1
Phramongkutklao College of Medicine, Military and Community
Medicine, Bangkok, Thailand. 2Armed Forces Research Institute of
Medical Sciences, Bangkok, Thailand. 3Royal Thai Army Institute of
Pathology, Bangkok, Thailand. 4Johns Hopkins Bloomberg School
Public Health, Epidemiology, Baltimore, United States
Presenting author email: r_rangsin@yahoo.com
Background: Thailand is a country with a continuing generalized
HIV epidemic. The Royal Thai Army conscripts represent a 10%
random sample of 21 year old men from throughout the
country. Thai military conscripts are representative of the young
population of Thai Men. We evaluated the prevalence and risk
factors for HIV infection among the RTA conscripts inducted in May
2011.
Methods: A cross-sectional study was conducted. All 40,000 male
conscripts inducted in May 2011 were invited to participate in
the study and to provide blood sample for HIV testing. A selfadministered questionnaire was used.
Results: Of 38,123 men who provided blood samples, 190 (0.50%)
men were HIV positive. There were 35,595 (93.36%) men who
completed the questionnaire information including 159 (0.45%) HIVpositives. Of 159 HIV positive men, 39.5,% 29.1, % and 2.0% reported
MSM behavior, sex with female sex workers and injection drug use,
respectively. The independent risk factors [adj.OR,95%CI] for HIV
infections were lower education [1.66(1.112.50)], type of actual
sexual relation [bisexual:1.27(0.672.41)/exclusive MSM:3.07(1.29
7.27)], sexual desire [with both sex:11.09(5.3522.98)/with only
men:25.65(10.7961.02)], sex in exchange for money [1.95(1.20
3.18)], and number of life time sexual partners (6)[1.51(1.042.20)].
Among 2,271 (7.1%) MSM, the independent risk factors for HIV
infection were graduate education level [3.51(1.0911.32)], sexual
roles [versatile:7.19(3.4015.21)/bottom:10.77(3.4233.89)], and
sex in exchange for money [1.97(1.023.81)]. The prevalence of
HIV infection of MSM was comparable in urban (3.2%) and rural
(2.1%) areas.
Conclusion: Sex between men was the major risk factor for HIV
infection in young Thai men. The other risk factors included
education level, number of sexual partners and sex in exchange
for money. The public health interventions for HIV prevention
especially among MSM are urgently needed both in urban and rural
areas.
95
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Table 1.
Track C Epidemiology and Prevention Science
Risk factors for HIV infection
Characteristic
Total N
HIV(%)
Crude OR (95%CI)
Adj. OR (95%CI)
29688
89 (0.3)
1
1
1930
26 (1.3)
4.54 (2.937.05)
1.27 (0.672.41)
339
32 (9.4)
34.67 (22.7952.73)
3.07 (1.297.27)
35041
105 (0.3)
Type of sexual relation
No
Bi sexual
Exclusive MSM
Sexual desire
Sex with women only
Sex with both men and women
Sex with men only
1
1
23 (7.2)
28 (15.6)
25.94 (16.2941.32)
61.29 (39.2395.77)
Total N
HIV(%)
Crude OR (95%CI)
Adj. OR (95%CI)
1470
25 (1.7)
1
1
104
11 (10.6)
6.84 (3.2614.32)
3.51 (1.0911.32)
1192
12 (1.0)
1
62
5 (8.1)
No
1527
33 (2.2)
1
1
Ever
680
24 (3.5)
1.66 (0.972.83)
1.97 (1.023.81)
Table 2.
318
180
11.09 (5.3522.98)
25.65 (10.7961.02)
Risk factors for HIV infection in MSM
Characteristic
Education (Yrs)
None-9
Graduate
Sexual role for sex with men
Top
Bottom
1
8.63 (2.9425.31)
10.77 (3.4233.89)
Sex in exchange for money
THAC0304
Need for innovative intervention strategies to reduce HIV
transmission among men who have sex with men in Andhra
Pradesh, India: following a large-scale HIV prevention
intervention
S. Khobragade1, P. Goswami2, L. Ramakrishnan2, B. George2,
R. Adhikary3, S. Ramanathan2, S. Mathew2, R. Hari Kumar4 and
V. Kodali4
1
FHI 360 India, Mumbai, India. 2FHI 360 India, Delhi, India. 3FHI 360
Washington DC, Washington, United States. 4National Institute of
Nutrition (NIN), Hyderabad, India
Presenting author email: pgoswami@fhiindia.org
Background: HIV sentinel surveillance data for Andhra Pradesh (AP)
showed an increasing HIV prevalence among men who have sex with
men (MSM) from 10.4% in 2006 to 23.7% in 2008. Avahan, the India
AIDS Initiative of the Bill & Melinda Gates Foundation implemented a
program focusing on MSM starting in 2004.
Methods: Two rounds of cross-sectional bio-behavioral survey were
conducted in four districts of AP in 2006(R1) and 2009(R2) as part of
the Avahan evaluation. A two-stage time location cluster sampling
method was adopted for both rounds to select men aged 18 years or
older who reported any type of sex with another male in the last past
month. Following informed consent, behavioral information was
collected through structured questionnaires, blood and urine specimens were tested for HIV and other STIs.
Results: A total of 1,621 MSM in R1 and 1,608 in R2 were
recruited. Between two rounds, there was a significant increase
in proportion of MSM reporting consistent condom use with
regular male partners (R1:31.9%; R2:54.6%, pB0.001) and with
Table 1. Multivariate analysis of selected biological and behavioral outcomes compared between R1 in 2006 (reference group) and
R2 in 2009 among MSM in Andhra Pradesh, India (N 1,621 in R1 and 1,608 in R2)
Outcomes
AOR*
95% CI
HIV prevalence
0.94
0.61.3
High Titer Syphilis (RPR 1:8)
Urethral Chlamydia and/or urethral Gonorrhea
0.98
0.68
0.52.0
0.22.0
Consistent condom use with regular male partners
44.2
21.989.1
Consistent condom use with other non-commercial male partners
28.3
17.546.5
Last time condom use with male partners from whom they bought sex
22.1
Last time condom use with male partners to whom they sold sex
1.59
6.771.9
0.803.2
*Adjusted Odds Ratio on socio-demographic factors such age, literacy, marital status, occupation, self-reported sexual identity.
96
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
other non-commercial male partners (R1:13.1%; R2:78.5%,
pB0.001). Significant increase also was observed in last time
condom use with male partner from whom sex services were bought
(R1:72.8%; R2:96.9%, p B0.001). No significant changes were seen in
HIV prevalence (R1:17.3%; R2:21.4%, p 0.100), high titer syphilis
(R1:3.4%; R2:4.0%, p0.376), urethral chlamydia and/or urethral
gonorrhea (R1:1.8.4%; R2:1.4%, p0.634) between rounds. The
proportion of MSM exposed to interventions increased between the
two rounds (R1:59%; R2:76%, p B0.001), as the proportion of MSM
reporting ever having undergone an HIV test (R1:12.1%, R2:78.1%,
pB0.001).
Conclusion: Despite increase in condom use and exposure to HIV
prevention services, HIV and STI prevalence show no significant
change. There is need for more investigation and operation research
to identify new and innovative approaches for reducing HIV
transmission among MSM in Andhra Pradesh.
FRLBX03
HIV prevalence, sexual risks and HIV knowledge among men
who have sex with men (MSM) in Malawi: understanding
risks among a stigmatized population and opportunities for
interventions
1
2
3
3
1
2
A. Wirtz , G. Trapence , V. Jumbe , E. Umar , S. Ketende , D. Kamba ,
M. Berry1,4, S. Stromdahl1,5, C. Beyrer1 and S. Baral1
1
Johns Hopkins Bloomberg School of Public Health, Epidemiology,
Baltimore, United States. 2Center for the Development of People,
Blantyre, Malawi. 3Malawi College of Medicine, Blantyre, Malawi.
4
Johns Hopkins Bloomberg School of Public Health, International
Health, Baltimore, United States. 5Karolinska Institutet, Public Health
Sciences, Stockholm, Sweden
Presenting author email: awirtz@jhsph.edu
Background: Malawi has a generalized HIV epidemic with approximately 11.0% of adults living with HIV, though preliminary data
highlight significant HIV-related vulnerabilities among key populations, such as MSM. There is limited understanding of vulnerabilities
among MSM; this study aimed to fill this gap and provide
population-based estimates of HIV prevalence and associations of
infection among MSM in Malawi.
Methods: 339 men reporting anal sex with another man in the
previous year were accrued into a respondent-driven-sampling study
from August 2011-March 2012 in Blantyre. Study activities included a
structured survey instrument and biological assessment of HIV and
syphilis.
Results: Participants were a mean age of 25.1yrs. (range: 1849),
46.6% were unemployed, over half were gay-identified (61.9%),
and 10.3% (35/339) were currently married to a woman. Participants
reported a mean of 3 male sex partners in the last 12mo. (range:
150). Concurrent relationships were common 30.4% (99/326)
reported recent partnerships with two or more men and 14.7%
(48/306) reported concurrent partnerships that included at least one
female. HIV prevalence was 14.8% (49/330); among those with HIV
infection, 91% (45/49) were unaware of their HIV status and
39.9% (19/39) had never tested for HIV. Nearly 60% (176/304)
reported that vaginal sex was the highest risk form of sex, indicating
low knowledge of transmission risk. Multivariate analysis demonstrated that age ]26yrs (aOR4.26, CI: 2.179.47), history of
imprisonment (aOR: 1.72; CI0.823.58), and having ]1 child (aOR:
2.25; 95% CI: 1.507.01) were associated with HIV infection, while
rural residency (aOR0.32; 95% CI: 0.110.93) and secondary education or higher (aOR: 0.81; 95% CI: 0.411.63) were inversely
associated.
Conclusion: As of May, 2012, the changing government in Malawi
publicly announced intention to decriminalize homosexuality. The
data here reinforce the need to take advantage of this opportunity to
provide services to MSM, given the limited HIV-related knowledge
and high-risk practices. This study demonstrates that MSM are an
important population in Malawi’s HIV epidemic and deserve targeted
HIV prevention services.
TUPDC0301
Willingness to take daily pre-exposure prophylaxis (PrEP)
among MSM in two HIV epicenters in the United States
L. Metsch1, I. Kuo2, M. Lalota3, G. Phillips Ii2, G. Cardenas1, A. Castel2,
D. Forrest1, T. West2, M. Pereyra1, Y. Jia2, M. Kolber4, J. Opoku2 and
M. Magnus2
1
University of Miami Miller School of Medicine, Department of
Epidemiology and Public Health, Miami, United States. 2George
Washington University Medical Center, Division of Infectious
Diseases, Washington, United States. 3Florida Department of Health,
Tallahassee, United States. 4University of Miami Miller School of
Medicine, Medicine, Miami, United States
Presenting author email: lmetsch@med.miami.edu
Background: We examined knowledge, attitudes, and practices
toward use of daily PrEP among MSM and factors associated with
their willingness to take PrEP if available and offered for free or
covered by health insurance.
Methods: Between AugustDecember 2011, MSM in two U.S.
metropolitan areas heavily impacted by HIV (Miami, Florida and
Washington, D.C.) were recruited and interviewed through venue
based sampling for the CDC National HIV Behavioral Surveillance
study. Multivariable logistic regression analysis assessed demographic, socioeconomic, drug use and sexual risk correlates of being
very willing to take PrEP for each city.
Results: The samples included 321 in Miami (median age 29;18%
black, 10% white, 71% Hispanic, 1% Other) and 323 in Washington
D.C. (median age32, 28% black, 49% white, 13% Hispanic, 10%
Other). Fifteen percent of men in Miami and 30% in Washington D.C.
had heard information about PrEP, few knew anyone who had
taken PrEP (3% in both cities), and none reported having taken it
themselves. Almost half (49%) of MSM in Miami and almost twothirds (61%) in Washington D.C. reported they would be willing to
take PrEP. In Miami, only non-injection drug use in the past year was
associated with decreased willingness to use PrEP (OR .59, 95%
CI (.36, .96). In Washington, D.C.,33 years of age (OR .45,
95% CI (.28, .74) and having fewer sexual partners (OR .57, 95% CI
(.33, .98) were associated with decreased willingness to use PrEP;
non-injection drug use (OR1.67, 95% CI (1.02, 2.73) was associated
with increased willingness to use PrEP.
Conclusion: Awareness and use of PrEP in these two US HIV
epicenters is low; innovative strategies are needed to inform and
educate MSM about this new prevention strategy. Willingness to use
PrEP may be impacted by drug use and sexual risk behaviors. Future
studies are needed to understand how non-injection drug use may
impact PrEP use.
THPDC0104
The MSM population in a conservative environment: Egypt
S. Elkamhawi1, O. Abaza1, E. Elghamrawy1, S. Abou Elmagd2,
H. Ramy2, S. Atallah3, N. Elkot4, M. Kamal5, F. Mawazini6, R. Helmy1
and C. Soliman1
97
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
1
FHI 360, Cairo, Egypt. 2Waay NGO, Cairo, Egypt. 3Befrienders NGO,
Cairo, Egypt. 4Hayat NGO, Cairo, Egypt. 5Ford Foundation, Cairo,
Egypt. 6Drosos Foundation, Cairo, Egypt
Presenting author email: selkamhawi@fhi-egypt.org
Background: HIV interventions targeting most-at-risk populations
(MARPs) in Egypt have focused primarily on behavior change through
awareness campaigns. The lack of information about the MSM
population continues to be a challenge for HIV prevention and care
efforts.
Methods: FHI 360 with (funding from the Drosos and Ford
Foundations) established three ‘‘comprehensive care centers’’ (CCCs)
to provide harm-reduction services for MARPs. Data were collected
and analyzed for all the MSM who visited the CCCs.
Results: From July 2008 to December 2011, 1,303 MSM visited the
CCCs. Of these, 92.7% were referred by peer-educators through
community outreach. The HIV prevalence among the MSM was 4.1%.
About 46% were 16 to 24 years old and more than half of them had
received some university education. Ever-being married to a female
was reported by 13.0% of the MSM, whereas 9.5% were divorced
and 22.7% had ‘‘a steady partner, but were not living together.’’
About 42.6% reported ‘‘ever-injecting drugs,’’ 69.0% shared needles
and 83.7% shared paraphernalia. Alcohol was consumed by 43.7%.
In the past year, about half of the MSM had commercial sex partners
and 93.6% had non-commercial sex partners. Moreover, 17.5%
reported exchanging sex for drugs. In the past six months, less than
one quarter of the MSM used a condom during sexual intercourse
with their regular partners and 31.9% used a condom with nonregular partners. About 70.7% were willing to use condoms,
however only 14.0% reported condom use during their last sexual
encounter.
Conclusion: Connections between MSM and the general population
have the potential to spread the HIV epidemic beyond the MARPs.
Unsafe injection of drugs and risky sexual behaviors among MSM
should be addressed in future programs. There is a need to expand
the CCC model for MARPs in Egypt.
C11 - Epidemiology of HIV in migrants
MOPDC0203
From assessment to action: HIV in migrant populations in
Europe
A. Pharris, T. Noori, G. Likatavicius and M. van de Laar
European Centre for Disease Prevention and Control (ECDC),
Programme for HIV/AIDS, STI and Blood-Borne Infections, Stockholm,
Sweden
Presenting author email: anastasia.pharris@ecdc.europa.eu
Background: Migrant populations from countries with generalised
HIV epidemics represent a considerable proportion of the heterosexually acquired cases of HIV/AIDS in EU/EEA (European Union/
European Economic Area) countries. A better understanding of the
epidemiology of HIV among migrants is essential to tailor HIV
prevention and treatment programmes.
Methods: Results from European HIV/AIDS surveillance data from
2010 and qualitative surveys on national HIV programmes and
policies were used to assess the situation of HIV in migrant
populations.
Results: Overall, one-third of the heterosexually acquired HIV cases
were diagnosed in individuals originating from countries with
generalised epidemics and this proportion varies by country, but is
60% in Belgium, Sweden, Malta, and the UK. Studies in France,
Track C Epidemiology and Prevention Science
Spain and the UK describe higher prevalence of late HIV diagnosis
(CD4 count B350 cells/mL3 at HIV diagnosis) in migrants compared to
non-migrants and in ethnic minorities compared to the non-minority
population. Half of EU/EEA countries report that they have legal,
regulatory and policy barriers for migrants to access HIV treatment,
care and support. Seventy-five percent of countries indicated that
migrants are an important subpopulation in the national response to
HIV. However, only 40% collect information on the uptake of HIV
testing and only 50% on access to ART among migrants.
Conclusion: Evidence suggests that, in some European countries,
migrants from countries with generalised HIV epidemics are disproportionally affected by HIV and do not access testing or treatment
services as readily as other populations. There is a need for concerted
action at a European level to gather better evidence for decisionmaking and to develop better measures of HIV transmission among
migrants after arrival to the EU/EEA in order to improve HIV
prevention resource allocation. There is also a need for strong
political leadership in order to further develop and expand programmes for migrants from countries with generalised HIV epidemics.
C12 - Epidemiology of HIV in other
populations including transgender
THPDC0202
Global burden of HIV infection among transgender persons:
a systematic review and meta-analysis
S. Baral, T. Poteat, A. Wirtz, S. Stromdahl and C. Beyrer
Center for Public Health and Human Rights, JHSPH, Epidemiology,
Baltimore, United States
Presenting author email: sbaral@jhsph.edu
Background: The term transgender generally refers to people whose
gender identity differs from birth sex. Transgender people exist on
every continent. Male to Female Transgenders(TG) have often been
included as a subpopulation of men who have sex with men(MSM) in
HIV research since many share risk behaviors with MSM, such
as anal intercourse, a much more efficient mode of HIV transmission
than penile-vaginal intercourse. In contrast to MSM, there has
been to date no systematic review of the global burden of HIV
among TGs.
Methods: This study included a systematic review of peer-reviewed
HIV prevalence published data characterizing the burden of HIV
among TG published between January 1,2000 and November
30,2011. Meta-analyses of these data compared HIV prevalence
among TG to that among reproductive age adults in each country.
Results: In all, 877 unique citations were reviewed including 39
studies that met inclusion criteria. HIV data among 11,066 TG women
in 10 low and middle income countries (LMIC) and 5 high income
countries (HIC) were found. The pooled global HIV prevalence was
19.1% (95% CI 17.420.7). In 7,197 TG from 10 LMIC, HIV
prevalence was 17.7% (95% CI 15.619.8); in 3,869 TG from 5 HIC,
HIV prevalence was 21.6% (95% CI 18.824.3). The odds ratio for
being infected with HIV among TG as compared to all reproductive
age adults across all 15 countries was 48.8 (95% CI 31.276.3); the
OR in LMIC was 50.0 (95% CI 26.594.3) and 46.3 (95% CI 30.370.7)
in HIC.
Conclusion: Male to female TG persons are at very high risk for
HIV infection in both low and high income countries. They are some
50 times more likely to have HIV infection than other adults of
reproductive age in the 15 countries for which data were available.
TG are an understudied but very at risk group for HIV and are clearly
in urgent need of HIV services.
98
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
Figure 1. TG Meta-Analysis.
C14 - Epidemiology of sexually
transmitted infections (STI) and HIV
TUAC0201
Evaluation of presumptive treatment recommendation for
asymptomatic anorectal gonorrhoea and chlamydia
infections in at-risk MSM in Kenya
H.S. Okuku1, E. Wahome1, S. Duncan1, A. Thiongo’1,
J. Mwambi1, J. Shafi2, A.D. Smith3, S.M. Graham1,4 and
E.J. Sanders1,5
1
Centre for Geographic Medicine Research-Coast, Kenya Medical
Research Institute (KEMRI), Kilifi, Kenya. 2University of Nairobi,
Mombasa, Kenya. 3Department of Public Health, University of
Oxford, Headington, Oxford, United Kingdom. 4University of
Washington, Seattle, United States. 5Nuffield Department of
Medicine, University of Oxford, Headington, Oxford
United Kingdom
Presenting author email: esanders@kilifi.kemri-wellcome.org
Background: In 2011, the World Health Organization (WHO)
recommended that at-risk MSM (reporting unprotected anal intercourse in the last 6 months, partner with STI or multiple partners)
should be presumptively treated for asymptomatic anorectal N.
gonorrhoeae (NG) and C. trachomatis (CT) infections. We evaluated
this recommendation amongst a large group of MSM sex workers in
Coastal Kenya.
Methods: We assessed the presence genitounirary and rectal
symptoms, and determined the prevalence and 3-month incidence
of urethral and rectal NG- and CT- infections by NAAT-screening of
urine and rectal swab samples collected from at-risk MSM followed
in a cohort study in Coastal Kenya. Men with syndromic or NAATconfirmed received cefixime (400 mg stat) and doxycycline (100 mg,
bd, 7 days), risk reduction counseling, and advice on partner
treatment.
Results: Of 277 at-risk MSM (97% of total meeting WHO criteria), 38
(13.7%, 95% confidence interval (CI) 918) had asymptomatic
infections, including 28 (10.1%, 95% CI714) who had asymptomatic
anorectal NG- or CT. Only 4 (1.4%, 95% CI 04) men had symptomatic
infections, including 3 that were NAAT-confirmed (2 NG- and 1 NG-CT
co-infection). Of 214 at-risk MSM re-screened at a median 93 days
(Inter quartile range 84103), 22 (10.3%) had an asymptomatic NG- or
CT-infection, including 11 men who were treated at baseline. The 3month incidence of any NG or CT infection was 37.0 (95% CI 24.8
55.3); any NG-infection, 12.3 (95% CI 6.224.7) and any CT-infection
27.8 (95% CI 17.544.1) per 100 person-years.
Conclusion: For every 10 at-risk MSM meeting criteria for presumptive treatment, 1 asymptomatic anorectal infection would be treated
in this population. Upon re-screening at 3 months, 1 out of 10 at-risk
MSM had asymptomatic NG- and CT- infections. Periodic presumptive treatment every 3 months should be considered for at-risk MSM
in the absence of NAAT screening.
TUPDC0103
Gonorrhea infections diagnosed among persons living with
HIV: cross matching surveillance registries to identify
potential opportunities for integrated partner servicesNew York City, Washington D.C., Miami/Dade County
and Arizona
M. Taylor1,2, J. Schillinger1,3, P. Pathela3, J. Skinner2, D. Newman1,
S. Braunstein3, C. Shepard3, T. Brewer1,4, T. Ahmed5, A. Griffin5 and
B. Furness5
99
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
1
(752/10,553) in NYC, 6.4% (142/2,211) to 6.7% (155/2,302) in DC,
2% (91/3,917) to 4% (165/4,265) in MDC, and 0.7% (31/4,400) to 3%
(91/3,486) in AZ.
Conclusion: Retrospective data integration identified many coinfected HIV/GC cases, and indicated HIV co-infection rates are
increasing. Real time access to integrated HIV and STD surveillance
would allow better targeting of public health interventions to
subgroups of the population posing highest risk for transmitting
HIV in their jurisdictions. Local staffing patterns and effectiveness
would need to be evaluated to determine the feasibility of
interventions such as integrated PS.
Centers for Disease Control and Prevention, Division of STD
Prevention, Atlanta, United States. 2Arizona Department of Health
Services, STD Program, Phoenix, United States. 3New York City,
Department of Health and Mental Hygiene, New York City
United States. 4Miami/Dade County Department of Health, Miami,
United States. 5HIV/AIDS, Hepatitis, STD and TB Administration,
District of Columbia, Department of Health, Washington,
United States
Presenting author email: mdt7@cdc.gov
Background: Persons living with HIV/AIDS (PLWHA) who acquire new
STDs pose a risk for enhanced transmission of both HIV and STDs.
Some state and local STD and HIV programs prohibit data sharing
that would identify these individuals due to concerns with data
security and confidentiality. Significant resources are dedicated to
partner services (PS) for syphilis cases however, due to resource
limitations, few if any gonorrhea (GC) cases in high morbidity areas
receive this intervention.
Objective: To describe the frequency of HIV co-infection among
gonorrhea cases in 4 cities/regions in the US with varied GC and HIV
epidemiology.
Methods: A probabilistic method was used to match the HIV and STD
surveillance databases at the New York City Department of Health
(NYC), Department of Health, Washington DC (DC), Miami/Dade
County Health Department (MDC), and Arizona Department of
Health Services (AZ). Person and diagnosis events from the matched
HIV-STD datasets included 20002008.
Results: During 20002008, 4.6% (9,471/205,689) of reported GC
cases occurred among persons with previously diagnosed (eg.
preexisting) HIVNYC (5.5%, 5,930/107,786), DC (7.3%, 1,312/
17,910), MDC (4%, 1,504/40,214), and AZ (2%, 725/39,779). Overall,
white male GC cases had the highest HIV co-infection in each
jurisdictionNYC (22%, 592/2,680), DC (11% 1,000/9,540), MDC (11%,
339/3,080), and AZ (7%, 397/5,501). The overall HIV-GC co-infection
rates increased over the study period from 3% (367/12,314) to 7%
Table 1.
TUPDC0105
Sexually transmitted infection incidence as a biomarker for
high risk sexual behaviour in individuals diagnosed with
acute HIV after entering care
A. Cope1, A. Crooks2, J. Kuruc2, A. Sugarbaker2,
L. Hightow-Weidman2, J. Eron2 and C. Gay2
1
University of North Carolina, Epidemiology, Chapel Hill, United
States. 2University of North Carolina, Medicine, Chapel Hill
United States
Presenting author email: acbarry@unc.edu
Background: Sexually transmitted infection (STI) diagnosis following
diagnosis of acute HIV infection (AHI) indicates on-going high-risk
sexual behavior and possible risk of HIV transmission. We assessed
predictors of STI acquisition and the effect of time since care entry
on STI incidence in AHI patients in care and receiving targeted,
consistent risk-reduction messaging.
Methods: Data on incident gonorrhea, chlamydia, trichomoniasis,
primary/secondary syphilis, demographic, and clinical risk factors
were collected for patients in care at the UNC Infectious Diseases
Demographics Stratified by Incident STI
Total Cohort
N
TOTAL
81
Median Age at Diagnosis (IQR)
25
%
]1 STI
N
%
25
(2133)
24
No STI
N
%
Bivariate p-value
56
(2130)
25.5
(2135.5)
0.3
0.2
Sexual Risk Group
Female
Heterosexual Male
MSM
9
11.1
2
8.0
7
12.5
10
62
12.3
76.5
1
22
4.0
88.0
9
40
16.1
71.4
Race/Ethnicity
Black
47
58.0
16
64.0
31
55.4
Non-Black
33
40.7
8
32.0
25
44.6
1
1.2
1
4.0
0
0.0
Missing
0.3
STI Diagnosis within 8 weeks Before AHI Diagnosis
Yes
27
33.3
15
60.0
12
21.4
No
Ever On ART
54
66.7
10
40.0
44
78.6
Yes
74
91.4
21
84.0
53
94.6
No
7
8.6
4
16.0
3
5.4
0.0007
0.1
On ART within 45 Days
Yes
62
76.5
17
68.0
45
80.4
No
19
23.5
8
32.0
11
19.6
0.2
100
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
United States. 6Johns Hopkins Medical Institutes, Baltimore
United States. 7Central Kentucky Research Associates, Inc., Lexington,
United States. 8New England Center for Clinical Research of
Massachusetts, LLC, New Bedford, United States
Figure 1. Sexually Transmitted Infection Crude Incidence Rates
and Robust 95% Confidence Intervals by Time Since Care Entry.
Clinic between 1/1/1998 and 11/30/2011 with an AHI diagnosis,
(defined as negative or indeterminate immunoassay and reproducibly detectable HIV by amplification methods). Poisson regression
models, using generalized estimating equations, were fit to estimate
incidence rates (IR) and robust 95% confidence intervals. The effect
of years since entering care on STI incidence was also estimated.
Results: Among 81 AHI patients (Table 1), 25 (31%) were diagnosed
with at least 1 incident STI over 335.7 person-years; 39 STIs were
diagnosed during follow-up (IR8.7/100 person-years). The median
time from care entry to first STI diagnosis was 456 days (IQR208
945). STI diagnosis at or immediately before AHI diagnosis was a
predictor of incident STI (p 0.0007). The majority of patients
(91%) were treated with antiretroviral therapy; 84% of those were
treated within 45 days. At STI diagnosis, 56% had viral load (VL)
below the limit of detection. Among treated and untreated patients
with detectable VL, the median at STI diagnosis was 6,846 c/mL
(IQR 40121,388). STI IRs decreased as time since AHI diagnosis
increased (Figure 1). An attenuated, decreasing trend remained
when controlling for sexual risk group, age, and STI within 8 weeks of
AHI diagnosis (adjusted p-for-trend0.09).
Conclusion: Despite regular HIV care, STI incidence was high among
this primarily young, MSM AHI cohort, particularly early after AHI
diagnosis. Early antiretroviral initiation may decrease HIV transmission given ongoing risk behavior despite risk-reduction messaging.
C15 - Epidemiology of viral hepatitis and
HIV co-infection
TUAC0501
Use of rapid testing to prospectively identify HCV
co-infection in populations with high HIV prevalence
S. Lee1, M. Roehler1, G. Guillon1, E. Schiff2, A. Delgado-Borrego2,
T. Friel3, A. La Marca4, R. Dickson5, M. Sulkowski6, J. Borders7,
G. Allen8, L. Kurtz1, K. Kardos1 and R. Gregg1
1
OraSure Technologies, Inc., Bethlehem, United States. 2University of
Miami, Miller School of Medicine, Miami, United States. 3Lehigh
Valley Hospital, Department of Medicine Research, Allentown,
United States. 4Therafirst Medical Center, Ft. Lauderdale,
United States. 5Dartmouth Hitchcock Medical Center, Lebanon,
Background: A rapid HCV test was recently approved and CLIAwaived by FDA and is now being deployed to identify HCV infection
in populations at risk for both HIV and HCV. The presence of HIV coinfection has been reported previously to reduce sensitivity of some
HCV antibody tests. We report here on the results of a study of the
efficacy of a rapid HCV test in identifying HCV infection in HIV
positive and HIV negative cohorts.
Methods: A total of 1660 subjects at risk for HCV infection, or with
signs and/or symptoms of hepatitis, were prospectively tested by the
OraQuick† HCV Rapid Antibody Test using fingerstick blood. Of these,
444 (26.7%) self-reported as HIV positive upon enrollment into the
study. Performance of the rapid test in HIV positive and negative
cohorts was assessed by comparison with HCV status determined by
laboratory testing from a contemporaneous venous blood draw,
using an algorithm of EIA, recombinant immunoblot assay (RIBA† )
and PCR.
Results: Of 444 HIV positive subjects, 211 (47.5%) were also HCV
positive, compared to an HCV seroprevalence of 41.8% (508/1216) in
HIV negative subjects. Among HIV positive subjects, intravenous drug
use (49.1%) and high risk sexual behavior (39.6%) were the most
prevalent risk factors. Agreement between the rapid test and
laboratory tests in identifying HCV infected subjects was indistinguishable between HIV positive (98.1%) and HIV negative (98.6%)
populations (p0.629).
Conclusion: The rapid test performed comparably to laboratory tests
for prospective identification of HCV infection in at-risk subjects.
Sensitivity of the OraQuick† rapid test for HCV antibodies was not
compromised in HIV infected individuals. The deployment of a rapid
HCV test may expand testing in populations at risk for both HIV and
HCV infection and may be an important tool in raising public health
awareness of HCV prevalence.
TUAC0502
Seroprevalence of HBV and HCV among children in the
Kilimanjaro region of Tanzania
F.J. Muro1, S.P. Fiorillo2, C. Odhiambo1, C.K. Cunningham3 and
A. Buchanan1,3,4
1
Kilimanjaro Christian Medical Centre, Moshi, United Republic of
Tanzania. 2University of Colorado, Denver, Division of Infectious
Diseases, Aurora, United States. 3Duke University Medical Center,
Division of Infectious Diseases, Department of Pediatrics, Durham,
United States. 4Duke Global Health Institute, Duke University,
Durham, United Republic of Tanzania
Presenting author email: ann.buchanan@duke.edu
Background: Data on HIV and hepatitis B virus (HBV) and hepatitis
C virus (HCV) co-infection among children in Africa are scarce.
We evaluated the seroprevalence of HBV and HCV among healthy
HIV-uninfected children and HIV-infected children in the Kilimanjaro
Region of northern Tanzania.
Methods: HBV and HCV markers were assessed on banked serum and
plasma samples from HIV-negative children ages 1 month to 18 years
and HIV-infected children on highly active antiretroviral therapy
(HAART) a minimum of six months from 1 to 16 years of age. HBV
markers included hepatitis B surface antigen (HBsAg), hepatitis B
surface antibody, and hepatitis B core antibody (HBcAb). Infection was
defined as a single positive HBsAg or HBcAb result. HCV infection was
assessed by anti-HCV ELISA. Validation studies were performed on all
assays prior to use and all were FDA-approved.
101
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Results: Samples from 560 children were available for testing. Of 394
HIV-negative children, 36 (9.1%) were HBV-infected, and of 161 HIVinfected children, 33 (20.5%) were HBV-infected. Children with HIV
were 2.6 times more likely to be HBV positive (95% CI 1.53, 4.29)
than children without HIV (p 0.0002). None of the 560 samples was
positive for anti-HCV antibody.
Conclusion: HBV seroprevalence is high among children in the
Kilimanjaro Region, with a significantly higher prevalence among
HIV-infected children. Routine screening for HBV should be performed
among HIV-infected children. Patients with co-infection require closer
monitoring of liver transaminases due to hepatic toxicities associated
with antiretroviral therapy, and must be provided with appropriate
HAART which will target both viruses. Catch-up immunization with
HBV vaccine should be considered for older HIV-infected children.
TUAC0503
Prevalence, incidence and determinants of HCV infections
among HIV-positive MSM attending a STI clinic, 19952010
A.T. Urbanus1, T. van de Laar2, R. Geskus3, J. Vanhommerig4,
M. van Rooijen4, J. Schinkel5, T. Heijman4, R. Coutinho6,7 and
M. Prins4,8
1
Public Health Service, Cluster of Infectious Diseases, Amsterdam,
Netherlands. 2VUmc, Amsterdam, Netherlands. 3Academic Medical
Center (AMC), Department of Clinical Epidemiology, Biostatistics and
Bioinformatics, Amsterdam, Netherlands. 4Public Health Service
Amsterdam, Amsterdam, Netherlands. 5Academic Medical Center
(AMC), Department of Clinical Virology, Amsterdam, Netherlands.
6
National Institute for Public Health and the Environment (RIVM),
Center for Infectious Disease Control, Bilthoven, Netherlands. 7Julius
Center for Health Science and Primary Care, Utrecht, Netherlands.
8
Academic Medical Center (AMC), Division of Infectious Diseases,
Tropical Medicine and AIDS (CINIMA), Amstedam, Netherlands
Presenting author email: aurbanus@ggd.amsterdam.nl
Background: Since 2000 there is growing evidence that HCV has
emerged as an STI among HIV positive MSM. Here we present a
15 year overview of the HCV epidemic among MSM visiting a large
STI clinic in the Netherlands.
Methods: During waves of the bi-annual cross-sectional anonymous
survey (19952010), participants were interviewed and tested for
HIV and HCV antibodies. Additional HCV RNA tests were performed in
all HIV-positive MSM. Determinants of HCV infection were analysed
using logistic regression. HCV incidence was estimated using the
window period from HCV RNA detection until HCV-antibody development. Phylogenetic analysis of obtained HCV NS5B sequences was
performed to determine HCV genotype and to characterise HCV
transmission networks among HIV-positive MSM.
Results: Anti-HCV prevalence among HIV-positive MSM gradually
increased from 2.8% in 1995 to 3.8% in 2003 and reached its peak in
2008 (17.3%). The HCV incidence was highest in 2006 (14.0/100 PY;
95% CI5.0237.69) and decreased thereafter, although not significantly. Fisting in 2007/2008 was more strongly associated (aOR 2.62,
95% CI1.205.71) with HCV infection than fisting in 2009/2010 (aOR
0.98, 95% CI 0.472.03). In addition, Chlamydia, IDU, UAI and age
were independently associated with HCV. Phylogenetic analysis
revealed a high degree of MSM-specific clustering from 2000
onwards. HCV prevalence among HIV-negative MSM remained stable
(around 0.5%, 20072010).
Conclusion: HCV prevalence among HIV-positive MSM significantly
increased untill 2007, but appears to be levelling off in recent years.
This levelling off might partly be explained by increased testing and
HCV treatment uptake. The effect of fisting became less strong over
time, but both risk factor analysis and phylogenetic analysis continue
to support ongoing sexual transmission of HCV among HIV-positive
Track C Epidemiology and Prevention Science
MSM. Monitoring of HCV in both HIV-positive and HIV-negative
MSM remains needed to guide prevention in order to halt this
epidemic.
TUAC0504
HCV genotype and HBV co-infection associate with HCV
clearance in HIV-positive subjects
Y. Dong1, C. Qiu1, X. Xia2, J. Wang1, H. Zhang3, Y. Wang3, X. Zhang1,4
and J. Xu1,4
1
Fudan University, Shanghai Public Health Clinical Center and
Institutes of Biomedical Sciences, Shanghai, China. 2Faculty of Life
Science and Technology, Kunming University of Science and
Technology, Kunming, China. 3Dali Municipal Centers for Disease
Control and Prevention, Dali, China. 4China CDC, State Key
Laboratory of Infectious Disease Prevention and Control
Beijing, China
Presenting author email: dongyuan5177@gmail.com
Background: Less is known about the correlates of HCV clearance in
Chinese injected drug users (IDUs) who are co-infected with HIV. And
it remains unknown whether HCV genotypes affect the spontaneous
clearance of HCV. This study was designed to determine which
factors could significantly affect the clearance of HCV and whether
the genotypes could exert different influences on the clearance.
Methods: The cross-sectional survey was carried out on 528 HIVpositive IDUs patients in Yunnan Province. Their information on
demographic, HIV infection route, HAART, TB and HBV coinfections,
CD4T cell counts, HIV and HCV viral loads, HCV genotypes, alanine
aminotransferase (ALT) levels was collected from participants.
Logistic regression was performed to identify the correlates for
HCV clearance defined as HCV seropositive and RNA negative.
Results: 456 out of 528 HIV-infected subjects (86.4%) were identified
as HCV seropositive, including 357 (78.3%) HCV RNA positive and 99
(21.7%) RNA negative. The HCV clearance was significantly associated
with the presence of chronic HBV infection (p B0.0001), higher
CD4T-cell counts (p B0.05) and was greatly reduced with higher
ALT levels (p B0.05). Interestingly, the clearance of HCV genotype 1
was enhanced in higher CD4T-cell counts (p 0.065), whereas the
clearance of HCV genotype 6 were dramatically facilitated by chronic
HBV infection (p B0.005), no significant association was identified
with the clearance of genotype 3.
Conclusion: Our results suggested that the reserved host immune
function and HBV competition could improve the clearance of HCV in
HIV-infected subjects whereas the damage level in liver suggested
the non-clearance of HCV; For the first time, we demonstrated that
the clearances of different HCV genotypes were facilitated by
different factors. These data have important implications for the
management of HCV/HIV coinfected subjects.
C16 - Epidemiology of other diseases and
HIV
MOAC0202
Impact of syndemics on people living with HIV in San
Francisco
P.L. Chu1, G.-M. Santos2, A. Vu3, I. Nieves-Rivera1, G.N. Colfax2,
J. Grinsdale4, S. Huang5, S. Philip6, S. Scheer3 and T. Aragon1
1
San Francisco Department of Public Health, Population Health
and Prevention, San Francisco, United States. 2San Francisco
102
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Figure 1.
PLWHA Syndemics & Poverty, San Franciso.
Table 1.
Syndemic Effects on PLWHA, San Francisco
Track C Epidemiology and Prevention Science
N (%) Virologically
Chi-square
Mean
Kruskal-Wallis
N
Suppressed
p-value
Viral Load
p-value
13006
1716
10662 (88)
1219 (76)
303
198 (68)
62107
31
12 (45)
58589
HIV and Number of Co-infections
HIV only
HIV and 1 Co-infection
HIV and 2 Co-infections
HIV and 3 or More Co-infections
0.0012
B0.0001
Department of Public Health, HIV Prevention Section, San Francisco,
United States. 3San Francisco Department of Public Health, HIV
Epidemiology Section, San Francisco, United States. 4San Francisco
Department of Public Health, Tuberculosis Control
San Francisco, United States. 5San Francisco Department of Public
Health, Communicable Disease Control and Prevention
San Francisco, United States. 6San Francisco Department
of Public Health, STD Prevention and Control Section
San Francisco, United States
Presenting author email: priscilla.chu@sfdph.org
Background: Syndemics are the presence of two or more diseases
interacting synergistically to exacerbate health outcomes within a
population. In San Francisco (SF), the Program Collaboration and
Service Integration (PCSI) project has prioritized the integrated
monitoring of syndemics among four communicable disease registriesHIV, tuberculosis (TB), Viral Hepatitis (VH), and sexually transmitted diseases (STD). We assessed the prevalence of co-occurring
infections within these registries and their impact on persons living
with HIV/AIDS (PLWHA).
Methods: Living SF HIV/AIDS cases were matched against seven
diseases (active TB, latent TB, hepatitis B, hepatitis C (HCV), syphilis,
gonorrhea, and chlamydia). Using chi-square, t-test, and Kruskal-
12307
15703
Wallis tests, we assessed demographic, HIV health status, and
neighborhood differences between those with HIV only versus HIV
plus at least one co-infection.
Results: Among PLWHA, syndemics were highest amonginjection drug
users (27%, pB0.0001), those with very high (100000) viral loads
(VLs) (26%, p0.0001), those not virologically suppressed (23%,
pB0.0001), homeless (23%, pB0.0001), African-Americans (21%,
pB0.0001), women, transgender (both 18%, p B0.0001), and ages
2029 (16%, p 0.0003). Co-infected PLWHA affected diverse
geographic areas, regardless of socioeconomic status. Syndemic rates
per 100000 population were highest in Castro (1219), South of Market
(670), and Tenderloin (665) neighborhoods (pB0.001) (Figure 1).
The mean VLs for PLWHA with syphilis, chlamydia, gonorrhea, HCV, or
latent TB were higher than for PLWHA with HIV only (all pB0.001).
There was a significant correlation with increasing number of coinfections and increasing mean VLs (pB0.001) (Table 1).
Conclusion: Syndemics are associated with poorer HIV health
outcomes among PLWHA. We found a significant ‘‘dose-response
relationship’’ between the number of co-infections and mean VLs.
Greater numbers of co-infections, demographic subgroups, and
certain geo-clusters were associated with poorer health outcomes,
underscoring the need to address multiple conditions in tandem in
an integrated health system.
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
C17 - Molecular epidemiology
MOAC0204
Using phylogenetic analysis to identify HIV transmission
channels among persons newly diagnosed with HIV-1
infection in Los Angeles County, 20092010
K. Sey, Y. Ma and N. Song
HIV Epidemiology Program, Los Angeles County Department of Public
Health, Los Angeles, United States
Presenting author email: esey@ph.lacounty.gov
Background: Evidence for HIV transmission channels, such as
between men who have sex with men (MSM), or between MSM
and heterosexual females, has traditionally been obtained from
epidemiological data. Newer techniques, such as phylogenetic
analysis of HIV sequence data, can provide biological evidence for
the transmission channels suggested by self-reports and case studies.
The objective of this study was to use phylogenetic analyses
to characterize HIV transmission channels in Los Angeles County (LAC).
Methods: The study population consisted of 1407 LAC cases newly
diagnosed with HIV-1 in 2009 and 2010 for whom genetic sequencing
data (pol region) derived from a specimen obtained within 3 months
of diagnosis was available. To identify transmission clusters, phylogenetic reconstruction was performed using a neighbor-joining tree
based on the Kimura-2 parameter model, and 1000 bootstrap
replications. Transmission clusters were defined as sequences that
had a common node of bootstrap values greater than 95% and
average genetic distance lower than 0.015 nucleotide substitutions
per site.
Results: Sixteen clusters, representing 49 cases, were identified. Each
of these clusters comprised 34 cases. All were subtype B. Of the
cases within these clusters, 86% were male, 49% were older than 30
years, 47% were Hispanic, 60% were US-born and 67% were MSM.
We identified 4 distinct clusters, namely ‘‘MSM Only’’ (56%), ‘‘MSM/
IDU’’ (6%), ‘‘MSM/ Female or Male Heterosexual’’ (6%) and finally
‘‘IDU/HET female’’ (6%).
Conclusion: The results of our phylogenetic analysis provide
biological evidence for the major HIV transmission channels that
have previously been established by traditional epidemiological data.
While this method is still relatively new and standardized criteria for
cluster identification remain largely undefined, our findings demonstrate that phylogenetic analysis has potential to serve as an
additional source of information to validate the descriptions of local
HIV epidemics inferred from self-reported behavioral data and case
studies.
MOPDC0204
High prevalence of HIV-1 intersubtypes multiple infections
in the metropolitan region of Sao Paulo, Brazil
E.R.M. Nunes1, J.T. Maricato2, J.P. Zukurov1 and L.M.R. Janini2
1
Federal University Sao Paulo, Medicine, Sao Paulo, Brazil. 2Federal
University Sao Paulo, Microbiology, Immunology and Parasitology,
Sao Paulo, Brazil
Background: The high number of recombinants detected in the HIV-1
pandemic can be an indication that infection with multiple subtypes
is common. Estimations about the frequency of multiple infections is
essential, especially in places where multiple subtypes co-circulate
together with a population that may have a high percentage of
individuals carrying virus resistant to HAART, which may interfere
with treatment to HIV infections and could lead to progression of the
disease.
Track C Epidemiology and Prevention Science
Methods: The present study investigated the presence of multiple
infections in a population composed of 47 patients undergoing
HAART enrolled in the National STD/ AIDS, the Ministry of Health,
Brazil. The detection of multiple infections was carried out using a
RFLP assay for the protease gene of the virus, which is capable of
distinguishing between an infection caused by a single or more than
one subtype of HIV-1 according to different patterns of enzyme
digestion. Samples exhibiting multiple infections were cloned,
sequenced and submitted to phylogenetic analysis for the protease
gene of HIV-1.
Results: According to the protease gene analysis we were able to
indentify 17 HIV-1 multiple infections out of 47 samples. Multiple
infections were analyzed and the majority was composed by
recombinant viruses (94%), and only one was composed of pure
viruses belonging to subtypes B and F (6%).
Conclusion: This is the first study that reports the prevalence of
multiple infections and intersubtypes recombinants in a population
undergoing HAART, enrolled in the STD Program sponsored by
Brazilian Ministry of Health and, therefore, with free access to
antiretroviral drugs. Cases of multiple infections speed HIV-1 genetic
diversity rates through recombination, and may help to generate
viruses showing a combination of resistance mutation profiles.
Considering the patients carrying multiple infections, it may lead
to an increased acquisition of drug-resistant isolates.
C22 - Capacity building for HIV
prevention research
THAC0505
Capacity building of law enforcement officers to handle sex
workers In Sri Lanka
H.M.J.P. Vidanapathirana1 and M. Sangeeth2
1
National HIV/AIDS Prevention Project, Ministry of Health, Nugegoda,
Sri Lanka. 2Posittive Women Net Work, Community Based
Organization, Colombo, Sri Lanka
Presenting author email: kavigaya@yahoo.com
Background: Sex workers are been arrested by police due to
soliciting and selling sex under the vagrancy ordinance in Sri Lanka.
There are some reports that sex workers are arrested by police while
they are keeping condoms. It has been observed that there were
some misunderstandings about condoms and that they are not
considered as a medical device. Special training was conducted for
training instructors in the police to educate this matter.
Methods: Three days participatory-based special training programme
were conducted for 206 training instructors to achieve the objective
in four instances. The training module was developed and included
with various sessions using different education methods including
role plays, group work and brain storming sessions. The pre and post
test questionnaire was used to assess the difference of knowledge,
attitude and willingness to support the national HIV/AIDS plan while
handling sex workers
Results: Total knowledge score on HIV transmission, prevention and
misconception of the police officers showed significant increase from
69.5(SD16.1) at pre intervention stage to post intervention stage
86.6(SD 13.08). Total attitude score on handling sex workers with
the intention of HIV prevention showed significant increase from pre
intervention to post intervention (P 0.001). Willingness to support
the national HIV/AIDS plan while handling sex workers indicated
significant increase from pre intervention to post intervention
(P0.0001). All officers have positive attitude towards condoms
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Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
and knowledge about vagrancy ordinance were improved after the
intervention.
Conclusion: The special training was effective to improve the
knowledge, attitudes about HIV/AIDS and improve the wiliness to
support national HIV/AIDS plan while correct handling sex workers. It
is recommended to provide necessary communication materials for
training instructors in island wide to carry out continuous education
for police officers.
C23 - Measuring and modeling the HIV
epidemic
MOPDC0305
Patient migration significantly impacts estimates of
engagement in HIV care and attainment of an undetectable
HIV-RNA level in a cohort of newly HIV-diagnosed
individuals
S. Rowan1,2, S. Johnson1, M. Thrun1,2, E. Daniloff3, D. Reirden4,
W. Burman1,2, E. Connick1 and E. Gardner1,2
1
University of Colorado Denver, Division of Infectious Diseases,
Denver, United States. 2Denver Public Health, Denver, United States.
3
Colorado Department of Public Health and Environment, Denver,
United States. 4The Children’s Hospital, Aurora, United States
Presenting author email: sarah.rowan@ucdenver.edu
Background: Engagement in HIV care is a dynamic process. We
sought to describe engagement-in-care over time in a newly HIVdiagnosed cohort.
Methods: Retrospective review of engagement-in-care among newlydiagnosed HIV-infected individuals at Denver Health and University
of Colorado Hospital, 20052009. Client-level data was obtained
from three public HIV providers, two clinical trial groups, and
mandated Colorado state HIV laboratory reporting databases.
Engagement in care required a visit or HIV-labs in a 6-month
interval. Documentation in the medical record was required for outof-state designation.
Figure 1.
Engagement-in-care five years after HIV diagnosis.
Figure 2.
Engagement-in-care, migration and death censored.
Results: From 20052009, 616 individuals were newly HIV-diagnosed;
9% were female, 34% Hispanic, 16% Black, and 78% men who had
sex with men. Within 6 months of HIV diagnosis, 76% of individuals
had at least one outpatient HIV-care visit. In a missing failure
analysis, 5458% of patients were engaged in care and 3337% had
HIV-RNAB200 copies/ml after 2.5 years (Figure 1). However, a
significant proportion of individuals moved out-of-state or expired
causing an underestimate of engagement in this analysis. Within 5
years of diagnosis 14% of individuals moved out-of-state and 4%
expired. Excluding these individuals, 71% of the cohort were engaged
in care and 48% had HIV-RNAB200 cps/ml 5 years after diagnosis
(Figure 2). Among those engaged in care, the percentage of
Figure 3.
Percentages of individuals HIV-RNA B200cps/ml.
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Abstracts of the XIX International AIDS Conference
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Track C Epidemiology and Prevention Science
individuals with HIV-RNA levels B200 cps/ml increased from 28% in
the first 6 months after diagnosis to 67% 5 years after diagnosis
(Figure 3).
Conclusion: In missing failure analyses, 36% of individuals had an
undetectable viral load 5 years after diagnosis but this increased to
48% after excluding individuals who expired or were known to move
out of state. Out-of-state migration accounted for 14% of individuals
who appeared to be non-engaged in care, a minimal estimate given
the strict out-of-state designation criteria. Systems to track migration
are needed to allow accurate assessment of engagement-in-care at
the population level.
THPDC0101
Sexual mixing patterns between men who have sex with
men in southern India: implications for modelling the HIV
epidemic and predicting the impact of targeted oral preexposure prophylaxis
K.M. Mitchell1, A.M. Foss1, H.J. Prudden1, M. Pickles1,2,
J.R. Williams2, H.C. Johnson1, B.M. Ramesh3,4, R. Washington3,5,
S. Isac3, S. Rajaram6, A.E. Phillips2, J. Bradley6,7, M. Alary6,7,
S. Moses4, C.M. Lowndes7,8, C.H. Watts1, M.-C. Boily2 and
P. Vickerman1,9
1
London School of Hygiene and Tropical Medicine, London, United
Kingdom. 2Imperial College London, London, United Kingdom.
3
Karnataka Health Promotion Trust, Bangalore, India. 4University of
Manitoba, Winnipeg, Canada. 5St. John’s Research Institute,
Bangalore, India. 6CHARME-India Project, Bangalore, India. 7Centre
Hospitalier Affilié Universitaire de Québec, Québec, Canada. 8Health
Protection Agency, London, United Kingdom. 9University of Bristol,
Bristol, United Kingdom
Presenting author email: kate.mitchell@lshtm.ac.uk
Background: In southern India, the identity of men who have sex
with men (MSM) is closely related to role taken in anal sex, but little
is known about sexual mixing between identity groups. Both role
segregation and assortative (within-group) mixing are known to
affect HIV epidemic size in other settings. This study aimed to explore
how different mixing patterns affect estimated HIV trends and
intervention impact for MSM in Bangalore.
Methods: Deterministic models describing HIV transmission between
three MSM identity groups (mostly insertive panthis/bisexuals (PB),
mostly receptive kothis/hijras (KH) and versatile double deckers
(DD)), were parameterised with data collected in Bangalore for the
evaluation of the Avahan intervention. These models were used to
explore four different mixing patterns (table). 300,000 randomly
Table 1.
Figure 1. A. Model-projected median HIV prevalence for fits to
group-specific HIV data in 2006 and 2009, shown separately for
each identity group and mixing pattern. Fitting bounds shown by
vertical lines. B. Percentage of HIV infections averted following a 5year PrEP intervention with 42% effectiveness and 60% coverage,
targeted at scenario without PrEP.
Mixing patterns
Number of
Median Q* for
How mixing was determined
fits
fits
Maximum
assortative
KH, DD, PB all have as many acts with members of the same group as constraints allow.
108
0.16
Setting plausible
DD have as many acts with other DD as constraints allow. KH have as many acts with PB as
159
0.00
301
0.16
430
0.40
Mixing pattern
constraints allow and vice versa.
Proportionate
Receptive acts distributed between groups in proportion to the number of insertive acts
offered by each group.
Disassortative
PB and DD have as few acts with members of the same group as constraints allow.
*measures assortativeness of mixing in the whole population. 1completely assortative; 0.5 completely disassortative.
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
sampled parameter sets were obtained from data ranges and used to
find multiple fits to group-specific HIV prevalence data in 2006 and
2009. Model fits were used to compare predicted HIV time trends.
To compare the impact of a new intervention scenario, condom use
was assumed to decline from high levels in 2010 due to condomintervention fatigue. Oral pre-exposure prophylaxis (PrEP) was
introduced in 2015, assuming 42% effectiveness (efficacy x adherence) and 60% coverage, targeted at KH and DD (the groups easiest
to reach).
Results: Large differences in levels of assortative mixing were seen
for fits identified using different mixing patterns (Table 1), but little
difference was projected in HIV prevalence trends (A). Different
mixing patterns gave somewhat different estimates for group-specific
impact of the PrEP intervention (B), but overall impact in the whole
MSM population was very similar (B10% difference in % infections
averted).
Conclusion: A variety of different mixing patterns are consistent
with the data. However, model predictions of future HIV epidemic
trends and overall impact of a targeted intervention are robust to
the different mixing patterns and intervention scenario explored
here.
C24 - Measuring and modeling the
effect and impact of HIV prevention
interventions
THAC0502
Modeling the impacts of a comprehensive community
empowerment-based, HIV prevention intervention for
female sex workers in generalized and concentrated
epidemics: infections averted among sex workers and adults
A. Wirtz1, C. Pretorius2, S. Sherman1, S. Baral1, M. Decker3,
M. Sweat4, C. Beyrer1 and D. Kerrigan5
1
Johns Hopkins Bloomberg School of Public Health, Epidemiology,
Baltimore, United States. 2Futures Institute, New Haven
United States. 3Johns Hopkins Bloomberg School of Public
HealthDepartment of Population, Family and Reproductive
Health, Baltimore, United States. 4Medical University of South
Carolina, Charleston, United States. 5Johns Hopkins Bloomberg
School of Public Health, International Health, Baltimore
United States
Presenting author email: awirtz@jhsph.edu
Background: Sex workers have endured a high burden of HIV
infection across concentrated and generalized HIV epidemics, with
a range of interventions implemented to varying degrees of success.
A comprehensive, community empowerment-based HIV prevention
intervention emphasizes sex worker mobilization to address structural factors related to sex worker rights and HIV risk, and typically
includes peer education, condom social marketing, and STI/HIV
screening and treatment. Meta-analysis demonstrated a 51% reduction in inconsistent condom use among female sex workers (FSWs)
associated with such interventions. We used a deterministic
model (Goals) to model the impact on HIV among FSWs and the
adult population, when the community empowerment interventions were scaled up among FSWs in Kenya, Thailand, Brazil,
and Ukraine.
Methods: Models were parameterized with published data or
provided by country experts and calibrated against UNAIDS estima-
Track C Epidemiology and Prevention Science
Figure 1.
Infections averted with FSW intervention scale-up.
tions. The intervention was increased from baseline coverage over a
5-year period (565% coverage in Kenya and Ukraine; 1070%
in Thailand and Brazil), while other HIV interventions were held
constant. Impacts are observed from 20122016 and compared to
status quo, when all interventions are held constant.
Results: Increasing intervention coverage among FSWs in Brazil
averted 1,830 infections among FSWs and 4,740 among adults
between 201216, compared to status quo. Increased coverage
averted a cumulative 10,800 FSW and 20,680 adult infections in
Kenya. In Thailand, 220 FSW and 730 adult infections were
cumulatively averted. A cumulative 2,220 infections among FSWs
and 6,920 infections among adults are averted with increased
coverage in Ukraine. Impacts vary and were influenced by HIV
prevalence in different risk groups, risk behaviors, and population
size.
Conclusion: The community empowerment intervention for FSWs
demonstrated impacts among sex workers and the adult population
epidemics across these distinct settings. Findings confirm the
centrality empowerment in prevention strategies, as the intervention
is rights affirming and may require fewer resources, compared to
other interventions.
THAC0504
Impact of behaviour change communication targeting the
bridging population of clients of female sex workers in India
D. Suryawanshi1, P. Swain2, R. Kumari3, T. Bhatnagar4, W. Zhou5,
S. Bharat1, M. Bhattacharya6, A. Pandey3 and M. Collumbien5
1
Tata Institute of Social Sciences (TISS), School of Health System
Studies (SHSS), Mumbai, India. 2National Institute of Health and
Family Welfare, Department of Statistics and Demography, New
Delhi, India. 3National Institute of Medical Statistics, New Delhi,
India. 4National Institute of Epidemiology-ICMR, Chennai, India.
5
London School of Hygiene and Tropical Medicine, Department of
Social and Environmental Health Research, London, United Kingdom.
6
National Institute of Health and Family Welfare, New Delhi, India
Presenting author email: drtarunb@gmail.com
Background: Clients of female sex workers (FSW) is key group in
India’s HIV prevention programme due to their bridging role in HIV
transmission to women in the general population. With limited
evidence on intervention effects, we evaluate the impact of Avahan’s
behaviour change communication strategy on consistent condom use
among clients of FSW.
Methods: We analyzed data from 2009 Integrated Biological and
Behavioural Assessment survey among clients of FSWs sampled at
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
hotspots using time-location-cluster-sampling in Andhra Pradesh,
Maharashtra and Tamil Nadu (n5045). We used propensity score
matching to estimate the impact of media messages on clients’
consistent condom use with all partners (except their spouse); having
heard/seen messages on condoms and on STIs were considered as
the exposures. We stratified the analyses by usual pick-up place
(street or brothel).
Results: Clients of street-based FSWs were older (31 vs 29.5 yrs,
pB0.05) and better educated (77% vs 61% secondary and above,
pB0.001) than clients at brothels. Exposure to messages on
condoms (95%) was too high to detect an association with condom
use. Exposure to STI messages was 77% among street-soliciting clients
compared to 51% among those frequenting brothels. Only among the
brothel-soliciting clients we could demonstrate an effect44% of
exposed clients used condoms consistently vs 30% among the
matched controls (p B0.001). The observed differential is most likely
due to the local environmentmore intense and varied exposure to
safer sex messages at brothels including stronger interpersonal
communication with FSWs more effectively negotiating condom use.
Conclusion: Media messages on STIs are not sufficient to change
clients’ behaviour. With no effect among the more educated clients
of street based sex workers, the results show that without an
enabling environment, clients will not act on information received.
More needs to be done to reach clients of sex workers, especially
those of street-based FSWs.
FRLBC05
Combination interventions for the prevention of HIV among
injection drug users: a complex systems dynamics model
B. Marshall1, M. Paczkowski2, B. Tempalski3, E. Pouget3, S. Friedman3
and S. Galea2
1
Brown University, Department of Epidemiology, Providence
United States. 2Columbia University, New York, Department of
Epidemiology, United States. 3National Development and Research
Institues. Inc., Institute for AIDS Research, New York, United States
Presenting author email: brandon_marshall@brown.edu
Background: Although combination prevention strategies are receiving growing attention, there is little evidence to inform their
implementation, particularly for injection drug-using (IDU) populations. We constructed a complex systems dynamic model to assess
various strategies for reducing HIV transmission among IDU.
Methods: We modeled HIV transmission in a dynamic network of
IDU and non-IDU over a thirty-year time period (19922021). In the
model, ‘‘agents’’ engage in risk behavior and interact with simulated
prevention interventions (i.e., needle and syringe exchange programs
[NSP], HIV testing, antiretroviral treatment [ART], substance abuse
treatment). The model was constructed to represent the adult New
York metropolitan statistical area (MSA) population, and calibrated
by comparing HIV prevalence and incidence against historical
validated MSA-level data. We obtained annualized incidence estimates from Monte Carlo simulations to examine the consequences
of different intervention scenarios on a hypothetical population of
150,000.
Results: The model closely approximated published 19922011 data
for HIV prevalence and incidence among IDU. Under current
scenarios, HIV incidence among IDU residing in the New York MSA
is estimated to be 3.7 per 1000 (95% CI1.06.3 per 1000) in 2021.
Scenarios in which coverage of only one intervention was increased
resulted in decreased HIV incidence at 2021, with expanded NSPs
showing the lowest incidence rate (2.4 per 1000), followed by
increased substance abuse treatment availability (2.8 per 1000),
earlier initiation of HAART and improved adherence (2.9 per 1000),
Track C Epidemiology and Prevention Science
and increased access to HIV testing (3.5 per 1000). Combining all
scenarios resulted in the largest absolute reduction in HIV incidence
(1.7 per 1000, 95% CI0.03.9 per 1000) by 2021.
Conclusion: Our results demonstrate that combination interventions
have the greatest potential to reduce HIV transmission among IDU.
Although further research is required to determine cost-effectiveness, combining and bringing to scale existing evidence-based
interventions may well be a highly effective strategy to reduce
new infections.
MOPDC0102
Modeling the impact of focused strategies on the cost and
effectiveness of TLC-Plus (or ‘Test and Treat’) in New York
City
J. Kessler1, J. Myers2, K. Nucifora1, N. Mensah2, A. Kowalski1,
M. Sweeney2, C. Toohey1, C. Shepard2, B. Cutler2 and S. Braithwaite1
1
NYU School of Medicine, Division of Population Health, New York,
United States. 2Department of Health and Mental Hygiene, Bureau of
HIV/AIDS Prevention and Control, New York, United States
Presenting author email: jason.kessler@nyumc.org
Background: The recent HIV Prevention Trial Network (HPTN)
study052 strengthens the evidence base for HIV treatment as a
prevention strategy. We developed an operations research model of
HIV prevention, with conservative effectiveness assumptions, to
assist decision-making by public health authorities. We evaluated
whether focused deployment of the ‘‘test and treat’’ strategy (i.e.,
TLC-Plus) among various populations would be cost-effective.
Methods: Using an epidemic compartmental model of HIV transmission, we simulated implementation of TLC-Plus strategies, including
immediate anti-retroviral therapy (ART). We evaluated the impact of
deployment among different populations. Outcomes included the
number of infections averted over 20 years compared to the base
case (no intervention) and the cost per infection averted. Base case
assumptions regarding HIV testing and the proportion infected but
undiagnosed were varied as a sensitivity analysis. We assume that a
baseline proportion (89%) of HIV-infected persons are diagnosed; we
make realistic assumptions about linkage to care, adherence, and
retention in care.
Results: Generalized implementation of a TLC-Plus strategy averted
19% of new infections (from 59,109 to 47,690) over 20 years with a
cost-per-infection averted of US$1.56 million. Focused deployment
of the prevention package to specific populations reduced the
absolute number of infections averted but often resulted in a
program with favorable value, defined as a cost-per-infection
averted BUS$360,000. A TLC-PLUS intervention with a budget of
approximately $22 million per year could prevent 5% of infections
over 20 years (compared to base case), whereas a budget of US$1
billion per year would be required to attain the maximum prevention
impact.
Conclusion: Focusing TLC-Plus strategies on specific high prevalence
populations or neighborhoods may be more favorable than generalized implementation given the lower cost per infection averted and
current budget limitations. The model supports ongoing efforts to
focus scale-up of TLC-Plus and early ART initiation for all persons
newly-diagnosed with HIV.
TUPDC0302
Perceptions and attitudes about PrEP among seronegative
partners and the potential of sexual disinhibition associated
with the use of PrEP
108
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
A. Tripathi1, O. Whiteside2, C. Scanlon2 and W. Duffus2
1
Epidemiology and Biostatistics, University of South Carolina,
Columbia, United States. 2South Carolina Department of Health
and Environmental Control, Bureau of Disease Control, Columbia,
United States
Presenting author email: duffuswa@dhec.sc.gov
Background: Preexposure prophylaxis (PrEP) is a promising biomedical strategy to reduce HIV transmission. However, many caveats
such as the potential risk of sexual disinhibition and non-compliance
need to be considered. The objective of this survey was to explore
the sociodemographic and behavioral factors associated with the
adoption of PrEP among both MSM and heterosexual seronegative
partners.
Methods: Pre-piloted self-administered survey was conducted
among seronegative partners in a Ryan White Clinic in South
Carolina from 20102011. Bivariate and multivariable analyses were
used to explore the data.
Results: A total of 89 seronegative partners completed the survey.
The median age was 42 years (IQR3250) and a majority were males
(56%), blacks (70%) and heterosexual (74%). A majority of respondents were willing to use PrEP, if available (94%); however, 26%
suggested that they would be more likely to have unprotected sex
with HIV-positive partner while using PrEP and 27% suggested that
it will be difficult to take daily dose of PrEP and consistently use
condoms as well. Multivariable results suggested that ‘inconsistent
use of condom with HIV-positive partner after knowing their status’
was more likely among males (aOR 10.43; 95% CI 2.6740.79) and
those with lower education (aOR 6.09; 95% CI 1.5923.41), whereas
it was less likely among those of older age (aOR 0.70; 95% CI 0.52
0.94) and MSM as compared to heterosexuals (aOR 0.21; 95% CI
0.050.87); and perception ‘condom is no longer needed while taking
PrEP’ was more likely among those who did not use condom during
last sexual intercourse (aOR 7.45; 95% CI 1.5735.45) and less likely
among those with higher HIV knowledge score (aOR 0.43; 95% CI
0.230.78).
Conclusion: There is high acceptability among seronegative partners
for PrEP. However, there is a substantial risk of sexual disinhibition
and non-compliance while using PrEP that may be reduced by
ongoing education.
WEPDC0206
A complex systems approach to evaluate HIV prevention in
metropolitan areas: preliminary implications for
combination intervention strategies
B. Marshall1,2, M. Paczkowski2, L. Seemann3, B. Tempalski4,
E. Pouget4, S. Galea2 and S. Friedman4
1
Brown University, Department of Epidemiology, Providence, United
States. 2Columbia University, Department of Epidemiology, New York,
United States. 3University of Houston, Department of Physics,
Houston, United States. 4National Development and Research
Institutes, Inc., Institute for AIDS Research, New York, United States
Presenting author email: brandon_marshall@brown.edu
Background: HIV transmission among injecting and non-injecting
drug users (IDU, NIDU) is a significant public health problem.
Continuing propagation in endemic settings and emerging regional
outbreaks have indicated the need for comprehensive and coordinated HIV prevention. We describe the development of a conceptual
framework and calibration of an agent-based model (ABM) to
examine how combinations of interventions may reduce HIV
transmission among drug-using populations.
Methods: A multidisciplinary team of researchers from epidemiology, sociology, geography, and mathematics developed a conceptual
Track C Epidemiology and Prevention Science
framework based on prior ethnographic and epidemiologic research.
An ABM was constructed and calibrated through an iterative design
and verification process. In the model, ‘‘agents’’ represent IDU, NIDU,
and non-drug users who interact with each other within risk
networks, engaging in sexual and, for IDUs, injection-related risk
behavior over time. Agents also interact with simulated HIV
prevention interventions (e.g., syringe exchange programs, substance
abuse treatment) and initiate antiretroviral treatment (ART) in a
stochastic manner. The model was constructed to represent the
New York metropolitan statistical area (MSA) population, and
calibrated by comparing output trajectories for various outcomes
(e.g., IDU/NIDU prevalence, HIV prevalence and incidence) against
previously validated MSA-level data.
Results: The model closely approximated HIV trajectories in IDU and
NIDU observed in New York City between 1992 and 2002, including a
steady decrease in HIV prevalence among IDUs. Exploratory results
are consistent with empirical studies demonstrating that the
effectiveness of a combination of interventions, including syringe
exchange expansion and ART provision, dramatically reduced HIV
prevalence among IDUs during this time period.
Conclusion: Complex systems models of adaptive HIV transmission
dynamics can be used to explore the collective benefits of
hypothetical combination prevention interventions. Future work will
seek to inform novel strategies that may lead to more effective and
equitable HIV prevention strategies for drug-using populations.
MOPDC0207
Gentrification and its effects on HIV/AIDS rates in D.C.
T. Ahmed1,2, A. Griffin3, T. West1 and G. Pappas1
1
District of Columbia Department of Health, HIV/AIDS, Hepatitis, STD
and TB Administration, Washington, United States. 2George
Washington School of Public Health and Health Services,
Epidemiology and Biostatistics, Washington, United States. 3District
of Columbia Department of Health, HAHSTA, Washington,
United States
Presenting author email: tashrik@gmail.com
Background: Monitoring and evaluation of prevention programs in
urban centers often disregard population transience and demographic shift. These factors are often confounding variables, and
need to be properly addressed to form a clear picture on
intervention efficacy over long periods of time. In DC, we investigate
the efficacy of prevention programs as a factor of HIV/AIDS rates in
the city, to determine the proportion of rate change in HIV attributed
to gentrification alone.
Methods: Ordinary Least Squares spatial regression was used to
determine the relationship between HIV/AIDS rates in each neighborhood by gentrification index. Other explanatory variables such as
mode of transmission and ethnicity were excluded from the analysis
due to high levels of spatial autocorrelation. The resulting regression
was a bivariate comparison between gentrification and HIV/AIDS
rates. Mapping and data analysis were conducted in ArcGIS# and
RTM respectively.
Results: 676 cases (representing 64% of all cases in 2010)
were mapped across 39 neighborhoods. The bivariate model created
by Ordinary Least Squares spatial regression reported a R2 value
of 32%. The correlation coefficient of r 0.51 shows a significant positive association between gentrification and HIV rates
(p B0.05).
Conclusion: Approximately 31% of the variation in neighborhood
rates of HIV/AIDS in DC can be explained by gentrification and
demographic shift alone. Thus, gentrification is a significant factor in
explaining how HIV/AIDS rates vary by neighborhood. The findings
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
underscore the need to consider gentrification when using M&E to
advise programmatic priorities to accurately how public health
interventions affect new diagnoses. Next steps will involve including
suburban data to track HIV/AIDS outcomes due to gentrification in
the metropolitan area.
Conclusion: Dentists appear potentially willing to perform
HIV screening within general practice settings. Patients? and
colleagues? perceptions appear important in shaping dentists?
attitudes and likely behavior concerning this service. These findings
may inform the targeting of patient and provider behavior change
interventions.
C25 - New HIV testing and diagnostic
strategies
THAC0102
More HIV positive infants and mothers identified through
HIV testing in immunization clinics
TUAC0304
Dentist’s willingness to offer oral HIV rapid testing: results
from a nationally representative survey
L.R. Metsch1, H.A. Pollack2, S. Abel3, C. Kunzel4, B. Greenberg5,
S. Messinger1 and M. Pereyra1
1
University of Miami Miller School of Medicine, Department of
Epidemiology and Public Health, Miami, United States. 2University of
Chicago, School of Social Service Administration, Chicago, United
States. 3Nova Southeastern University, College of Dental Medicine,
Ft. Lauderdale, United States. 4Columbia Mailman School of Public
Health, Sociomedical Sciences, New York, United States. 5New Jersey
Medical School, UMDNJ, New Jersey Dental School, Newark,
United States
Presenting author email: lmetsch@med.miami.edu
Background: Identification of undiagnosed persons with HIV infection
is a public health challenge. The 2006 CDC guidelines recommend
wide spread screening in a variety of health care settings. Prior
research highlights the potential of the dental care setting as a
promising venue for HIV screening of otherwise untested individuals.
Methods: We performed a nationally representative survey of
general dentists which examined barriers and facilitators to offering
oral HIV rapid testing at chair side (n 1802, 70% response rate).
Sixty-three percent of dentists indicated they were somewhat or very
willing to rapid testing in the next year. We examined dentists?
willingness to perform such testing using multivariable logistic
regression controlling for potential confounders (age, gender, and
race/ethnicity).
Results: Dentists’ willingness to offer rapid testing in the next year was
positively associated with dentists? positive attitude regarding patient
acceptance of testing (AOR 3.5; CI 2.7, 4.3). Agreement with the
statement ‘‘my colleagues’ perception of me as a health care provider
would improve’’ was also positively associated with willingness to
offer testing (AOR2.7 for each unit increase in 4-point agreement
scale; CI 2.2, 3.2). Finally, dentists? agreement with the importance
for all persons at high risk to get tested for HIV annually was positively
associated with willingness to offer testing (AOR 1.7 for each unit
increase in 4-point agreement scale; CI 1.4, 2.0).
E.J. Schouten1, M. Sinunu2, N. Wadonda3, E. Kajawo1, M. Eliya3,
F.M. Chimbwandira3 and S.E. Kellerman4
1
Management Sciences for Health (MSH), Lilongwe, Malawi. 2Boston
University School of Public Health, Boston, United States. 3Ministry
of Health, Lilongwe, Malawi. 4Management Sciences for Health
(MSH), Centre for Health Services, Arlington, United States
Presenting author email: eschouten@msh.org
Background: In July 2011, Malawi initiated Option B-plus, in which
all HIV-positive pregnant women are offered lifelong ART, regardless
of clinical stage or CD4 count. From August-December 2011, we
evaluated Malawi’s national PMTCT program through an immunization clinic surveillance project designed to obtain population-based
vertical transmission rates.
Methods: InfantsB3 months old and their care-givers (primarily
mothers) attending the first immunization visit at one of 53
randomly-selected immunization clinics in four Malawi districts were
invited to participate and surveyed on maternal HIV testing and
PMTCT experience. Infant dried blood spots (DBS) were tested by
ELISA to determine maternal seropositivity (HIV-exposed). We
compared mothers’ responses about previous HIV testing with the
results of the ELISA test to establish the additional number of infants
and mothers in need of HIV care that could be identified if HIV
testing was introduced in immunization clinics.
Results: 5,545 linked DBS samples and surveys were collected. The
reported uptake of HIV testing during pregnancy was high; 89% of
women either tested during their pregnancy or already knew their
HIV (infected) status. The detailed testing history of the mothers and
the ELISA results of the infants are given in the table. In addition to
the 607 infants that were reported to be exposed to HIV (on the
basis of self-reported positive HIV-test result of the mother during or
before the last pregnancy) we found 207 (an additional 34%) infants
with ELISA-positive DBS in women that had never been tested or
tested HIV-negative before or during the pregnancy.
Conclusion: In this population with a high uptake of HIV testing in
pregnancy, testing infants in immunization clinics increased casefinding of HIV-infected infants (and mothers) by 34%. HIV testing in
immunization clinics could be effective in increasing identification of
infants and mothers in need of HIV care.
Table 1. Testing history mother and HIV-ELISA test results
Testing history of mother
Number of mothers
Positive HIV ELISA result in infant
Never tested
179 (3%)
17 (9.5%)
Negative HIV test before this pregnancy
277 (5%)
19 (6.9%)
Negative HIV test result during the pregnancy
Positive HIV test (any time)
Don’t know
No answer
Total
4,353 (79%)
171 (3.9%)
607 (11%)
561 (92.4%)
45 (1%)
83 (1%)
11 (24.4%)
15 (18.1%)
5,545 (100%)
794 (14.3%)
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
TUPDC0101
Tracing sexual contacts of HIV-positive individuals in
Taizhou, eastern China
H. Lin1, N. He1, Y. Ding1, W. Zhu2 and R. Detels3
1
Department of Epidemiology, School of Public Health, Fudan
University and The Key Laboratory of Public Health Safety of Ministry
of Education, Shanghai, China. 2Department of Epidemiology, School
of Public Health, Fudan University and The Key Laboratory of Public
Health Safety of Ministry of Education, Los Angeles, United States.
3
Department of Epidemiology, School of Public Health, University of
California, Los Angeles, United States
Presenting author email: linhaijiang@hotmail.com
Background: More than 400,000 persons living with HIV in China are
estimated to be unaware of their infections, in spite of tremendous
efforts in scaling up HIV testing. Identifying persons with undiagnosed HIV infection and linking them to medical care and prevention
services continues to be a priority for HIV prevention and control.
This study was to identify new HIV infections by tracing sexual
contacts of HIV-infected cases and to elucidate sexual network
characteristics among them and their sexual contacts.
Methods: All newly reported HIV cases from 20082010 in Taizhou
Prefecture were invited to participate in a contact tracing survey.
Each HIV positive participant was to provide detailed contact
information up to a maximum of eight sexual contacts. This group
was approached for voluntary HIV counseling and testing. This
process was repeated until no more sexual contacts were reported or
tested positive.
Results: A total of 463 HIV cases were newly reported during this
study period. Among them, 398 (86.0%) HIV cases participated in the
survey and served as ‘‘index cases’’, including an initial 290 cases who
were identified from routine surveillance programs and 108 cases
from the contact tracing survey. Of the total of 1,403 contactable
sexual contacts, 320 (22.8%) received HIV testing and 125 (39.1%)
tested positive for HIV. Willingness to receive HIV testing was high
among spouses and long term heterosexual or homosexual partners
but extremely low among casual and commercial sex partners of
index cases. Consistent condom use was rare for all participants.
A total of 290 independent sexual network components were
constructed, with high complexity.
Conclusion: Contact tracing is useful for identifying new HIV
infections from spouses or long term sexual partners of HIV-infected
individuals. The complicated sexual networks existing between and
beyond HIV-infected persons provide opportunities for rapid spread
of HIV in such areas.
THPDC0103
Faster and integral HIV diagnosis among MSM in the HIV/
AIDS program of Mexico City (HIVPMC): necessary but not
sufficient
L. Juárez-Figueroa1, A. Gonzalez-Rodrı́guez2, J. Casillas3, E. Rodrı́guezNolasco2 and P. Iracheta2
1
HIV Laboratory, HIV Program of Mexico City-Condesa Clinic, Mexico
D.F., Mexico. 2HIV Program of Mexico City-Condesa Clinic, Mexico,
Mexico. 3Condesa Clinic, Medical Directorate, Mexico, Mexico
Presenting author email: luisjuarez@insp.mx
Background: Men who have sex with men represent the majority of
clients receiving HIVPMC/VCT services. In 2010 HIVPMC/Condesa
Clinic started a faster one-stop HIV/STI diagnosis during the first VCT
visit based on rapid HIV test and parallel EIA for HIV/STI diagnosis.
The laboratory also supports provider-initiated HIV testing activities
among inmates, street male sex workers, and other groups at risk.
Track C Epidemiology and Prevention Science
Table 1. Prevalence percent of HIV, Hepatitis B and C and
Syphilis among 7,382 men who answered a risk questionnaire
Anti-Tp
HIV
Heterosexual (25%)
MSM (75%)
6%
19%
HbsAg
Anti-HCV
VDRL
1%
1%
1%
3.7%
1%
6%
Note: Transgender MtW showed 22% HIV prevalence. Men who did
not answered risk questionnaire (n 943) showed 25.6% HIV
prevalence.
Table 2. Prevalence percent of HIV, Hepatitis B and C and
Syphilis among 2, 654 women who answered a risk questionnaire
HIV
HbsAg
Anti-HCV
Anti-TPVDRL
3%
0.1%
0.3%
0.7%
Note: Women who did not answered risk questionnaire (n 718)
showed 2.1% HIV prevalence.
HIV/STI prevalence in 12,697 VCT clients in Mexico.
Methods: During 2011, 8,325 men and 4,372 women were tested.
Since the fall 2011, initial CD4 counting in HIV clients, also done at
first visit, favoured a rapid HIV infection staging. In 2012 HIV viral
load analysis, required in Mexico for ART initiation, was added to the
first laboratory visit studies.
Results: The integral HIV/STI diagnosis at the first VCT visit reduced
the time elapsed, between the first HIV detection with a rapid test or
ELISA and completion of laboratory studies necessary for starting
ART. The attendance of vulnerable groups to VCT at Condesa Clinic
increased by 51% during 2011. Sixty percent of new detected
PLWHIV did not return for follow up and treatment as shown by the
national HIV database SALVAR.
Table 1 shows HIV/STI prevalence from clients who answered a risk
questionnaire.
Conclusion: Until recently the lack of a fast diagnosis contributed to
late ART initiation, thus favoring HIV transmission and increased
incidence of morbidity and mortality. A new fast and Integral HIV/STI
diagnostic approach promoted HIV VCT, increasing testing demand
while reducing desertion related to laboratory delays. This model
should be expanded to HIV clinics in other states showing similar
epidemic trends. However, now we have clear evidence of the
number of non-returning patients which points to the need for
focused specific actions to promote opportune ART access. Additionally to individual post-test counseling, innovative personalized
follow-up could be also addressed in non returning patients.
C26 - Methods for detecting recent HIV
infections
MOAC0203
HIV incidence determination in clade B epidemics: a multiassay approach
O. Laeyendecker1,2, R. Brookmeyer3, M. Cousins4, C. Mullis2,
J. Konikoff3, D. Donnell5, C. Celum6, S. Buchbinder7, G. Seage8,
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
G. Kirk9, S. Mehta9, J. Astemborski9, L. Jacobson9, J. Margolick10,
J. Brown11, T. Quinn1,2 and S. Eshleman4
1
NIAID, LIR, Baltimore, United States. 2Johns Hopkins University
Baltimore Marland, Medicine, Baltimore, United States. 3School of
Public Health, University of California at Los Angeles, Department of
Biostatistics, Los Angeles, United States. 4Department of Pathology,
Johns Hopkins Univ. School of Medicine, Baltimore, United States.
5
Fred Hutchinson Cancer Research Center, Vaccine and Infectious
Disease Division, Seattle, United States. 6Departments of Global
Health and Medicine, University of Washington, Seattle, United
States. 7San Francisco Dept. of Health, San Francisco, United States.
8
Harvard School of Public Health, Dept. of Epidemiology, Boston,
United States. 9Johns Hopkins Bloomberg School of Public Health,
Dept. of Epidemiology, Baltimore, United States. 10Johns Hopkins
Bloomberg School of Public Health, Dept. of Molecular Microbiology
and Immunology, Baltimore, United States. 11School of Public Health,
University of California at Los Angeles, Dept of Epidemiology,
Los Angeles, United States
Presenting author email: olaeyen1@jhmi.edu
Background: Accurate methods for estimating HIV incidence are
needed to track the epidemic, identify high-risk groups, and evaluate
HIV prevention interventions. We evaluated a multi-assay algorithm
(MAA) for identifying recent HIV infections and estimating population-level incidence.
Methods: We analyzed 1,782 samples from 709 adults in the United
States with known duration of HIV infection (08 years postseroconversion; HIVNET 001, MACS, and ALIVE cohorts). The MAA
included the BED capture immunoassay (BED-CEIA), an antibody
avidity assay, HIV viral load, and CD4 cell count. Logistic regression
with cubic splines was used to model the probability of being
classified as recently infected by the MAA. We calculated the window
period of the MAA (mean duration of time that individuals were
classified as recently infected). We compared the accuracy of
the BED-CEIA and the MAA for identifying recent infections. In the
HIVNET 001 Vaccine Preparedness Cohort, we directly compared the
MAA incidence estimate (cross-sectional analysis of samples from
the 18-month visit), to the observed incidence based on analysis of
HIV seroconversion during follow-up.
Results: The MAA window period was 141 days (95% CI 94150
days). Among individuals infected 1 year, 17.2% and 0.4% of 1,474
samples were misclassified as recent by the BED-CEIA and MAA,
respectively. Among individuals infected 5 years, 13.6% and 0% of
345 samples were misclassified as recent by the BED-CEIA and MAA,
respectively. In HIVNET 001, the annual incidence estimate based on
the MAA was 0.97% (95% CI0.51%1.71%), which is essentially
identical to the incidence observed in longitudinal follow-up of the
cohort (1.04%, 95% CI0.70%1.55%).
Conclusion: The MAA is sensitive for detecting recent HIV infection,
has a low rate of false-recent misclassification, and accurately
estimated HIV incidence in a cohort study. The MAA is potentially
a powerful tool for determining HIV incidence in clade B epidemics.
Track C Epidemiology and Prevention Science
B.S. Parekh1, Y.T. Duong1, D.L. Ellenberger1, C. Sexton1 and
R. Nkambule5
1
U.S. Centers for Disease Control and Prevention, Center for Global
Health, Division of Global HIV/AIDS, Atlanta, United States. 2ICAP at
the Mailman School of Public Health at Columbia University
New York, United States. 3US Centers for Disease Control and
Prevention, Swaziland, Mbabane, Swaziland. 4Fred Hutchinson
Cancer Research Center, Seattle, United States. 5Ministry of
Health-Swaziland, Mbabane, Swaziland. 6Columbia University,
ICAP, Swaziland, Mbabane, Swaziland
Presenting author email: eso7@cdc.gov
Background: Swaziland has the highest estimated national HIV
prevalence rates in the world. The Swaziland HIV Incidence
Measurement Survey (SHIMS) provides the first national-level HIV
incidence estimates based on prospectively observed seroconversions among participants in a population-based longitudinal
cohort.
Methods: A nationally representative sample of men and women,
age 1849, underwent household-based, rapid HIV testing from
December 2010June 2011, including counseling to reduce HIV
infection risk. Socio-demographic and behavioral characteristics
were also assessed through a questionnaire survey. HIV-uninfected
individuals were invited to enroll in a cohort and retested for HIV
and surveyed again approximately six months later. Longitudinal
incidence was calculated as events/person-years [PY] 100%.
Results: A total of 18,154 men and women, representing approximately 7% of the adult population, were surveyed, and 11,944 tested
HIV-negative and enrolled in the cohort. Among these, 10,949
(91.7%) were retested for HIV after a mean follow-up of 6.5 months,
resulting in 6,054 PY of observation. There were 146 seroconversions,
resulting in a weighted, national HIV incidence estimate of 2.4% (95%
CI, 2.12.7%). Incidence was higher in women (3.1%) than in men
(1.7%), overall, and was highest among women 2024 yrs (4.2%) and
men 3034 yrs (3.1%).
Conclusion: The highest HIV incidence rate (4.2%) in Swaziland is
among women 2024 yrs. Among men, the peak HIV incidence
rate (3.1%) occurs among those 10 years older. Study-related risk
reduction counseling may have extraneously altered participants? risk
behaviors and affected the observed incidence rates. These findings
reinforce the need for effective HIV prevention interventions, such as
voluntary medical male circumcision, which provides a direct
protection against HIV acquisition for men and an indirect protection
for women. As HIV prevalence may remain high independent of HIV
incidence rates, efforts to diagnose and treat persons already HIVinfected with antiretroviral therapy, are also paramount to curb
Swaziland?s severe HIV epidemic.
MOPDC0206
Incorporating incidence surveillance as part of national HIV
surveillance in the United Kingdom: closer tracking of
transmission
C29 - Determining HIV incidence
FRLBX02
Estimating national HIV incidence from directly observed
seroconversions in the Swaziland HIV Incidence
Measurement Survey (SHIMS) longitudinal cohort
J.B. Reed1, J. Justman2, G. Bicego3, D. Donnell4, N. Bock1,
H. Ginindza5, A. Koler2, N. Philip2, M. Makhanya3, C. Mlambo6,
A. Aghaizu1, M. Kall1, R. Smith1, J. Tosswill2, G. Murphy2 and
V. Delpech1
1
Health Protection Agency, HIV/STI Department, London, United
Kingdom. 2Health Protection Agency, Virus Reference Department,
London, United Kingdom
Presenting author email: valerie.delpech@hpa.org.uk
Background: HIV in the United Kingdom is concentrated in distinct
population sub-groups. Monitoring changes in transmission patterns
among these groups informs prevention and testing efforts. We
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
present HIV new diagnoses and alongside novel incidence surveillance data in England and Northern Ireland.
Methods: National surveillance of new diagnoses in adults in
England and Northern Ireland between January 2009 and June
2011 linked an avidity test. The Recent Infection Testing Algorithm
(RITA) utilises the avidity result adjusted for baseline CD4 count and
AIDS diagnosis to identify infections that probably acquired in the
preceding 6 months.
Results: 14,682 adults were diagnosed with HIV over the period45%
were men who have sex with men (MSM), 51% were heterosexual,
and 2% were IDUs. One in ten was aged 1529, 33% aged 2534,
42% aged 3549, and 15% aged 50. Over the 30 months, new
diagnoses in MSM increased as heterosexuals declined. A RITA result
was available for 33% (4,877) of new diagnoses (these persons had
similar demographic characteristics compared to those not tested).
Overall, one in six (15%) had recently acquired their infection. Recent
infection was more common in younger adults (25% persons aged
1524 and 20% persons aged 2534). MSM had the highest
proportion of recent infections (23%), followed by heterosexuals
(10%) and people who inject drugs (4%). One in three (31%) MSM
aged under 35 acquired their infection recently, compared to one in
seven (13%) aged over 50. Among heterosexuals, 20% of women
aged 1524 and 15% of men aged 2534 had recently acquired their
infection.
Conclusion: Surveillance data on new HIV diagnoses coupled with
results from RITA indicate high rates of ongoing transmission among
MSM, particularly in young MSM. Transmission patterns among
young heterosexuals must also be observed closely and in the
context of testing patterns.
C30 - Measuring and modeling the
impact of treatment for prevention
THAC0203
The prospects of elimination of HIV with test and treat
strategy
M. Kretzschmar1,2, M.F. Schim van der Loeff3, D. De Angelis4 and
R.A. Coutinho1,2
1
RIVM, Centre for Infectious Disease Control, De Bilt, Netherlands.
2
University Medical Center UtrechtJulius Centre for Health Sciences
and Primary Care, Utrecht, Netherlands. 3Public Health Service
Amsterdam, Division of Infectious Diseases, Amsterdam,
Netherlands. 4MRC Biostatistics Unit, Cambridge,
United Kingdom
Presenting author email: mirjam.kretzschmar@rivm.nl
Background: In recent years there was much debate in the
public health community about the prospects of eliminating HIV
from high endemic countries by a test and treat strategy. This
strategy entails regular HIV testing in the entire population and
starting antiretroviral treatment (ART) immediately in all who are
found to be HIV infected. The rationale for this approach is the
strongly reduced probability of onward transmission when the viral
load in blood is reduced to undetectable levels by successful ART.
Methods: We investigated under what conditions of testing coverage
and adherence to treatment elimination of HIV is feasible. We
extended the model by Granich et al. (2009) to incorporate a more
accurate description of disease progression and variable infectivity.
This deterministic compartmental model describes the progression
of HIV infection through a series of 3 stages. We used data from the
CASCADE study to estimate survival distributions with and without
Track C Epidemiology and Prevention Science
Elimination thresholds.
ART. We derived explicit expressions for the basic reproduction
number and the elimination threshold. Using data about incidence of
HIV during the exponential growth phase of epidemics in various
populations we investigated for which of these populations elimination is within reach.
Results: With the optimistic assumptions of Granich’s paper the
elimination threshold lies at 60% testing coverage if adherence to
subsequent treatment is 100%. If only 5% of treated persons drop
out of treatment per year, testing coverage has to be 100% to reach
elimination. With a more realistic assumption of variable infectivity
elimination is not possible for the situation in South Africa.
However, for populations with basic reproduction number below
3, elimination is within reach for annual testing coverage of around
50%.
Conclusion: Elimination is only feasible for populations with low
basic reproduction numbers or if the reproduction number is
lowered significantly as a result of other additional interventions.
THAC0204
Treatment as prevention for HIV in South Africa: different
models show consistency in occurrence, but difference in
timing of elimination and the overall impact of the
intervention
J.A.C. Hontelez1,2,3, M.N. Lurie4, T. Bärnighausen3,5, R. Bakker1,
R. Baltussen2, F. Tanser3, T.B. Hallett6, M.-L. Newell3 and S.J. de Vlas1
1
Erasmus MC, University Medical Center Rotterdam, Public Health,
Rotterdam, Netherlands. 2Radboud University Nijmegen Medical
CenterNijmegen International Center for Health Systems Research
and Education (NICHE), Nijmegen, Netherlands. 3Africa Centre for
Health and Population Studies, University of KwaZulu-Natal,
Mtubatuba, South Africa. 4Brown University Warren Alpert School of
Medicine, Providence, United States. 5Department of Global Health
and Population, Harvard School of Public Health, Boston,
United States. 6Imperial College London, London, United Kingdom
Presenting author email: j.hontelez@erasmusmc.nl
Background: Treating all HIV infected patients with antiretroviral
therapy (ART) has been suggested to eliminate HIV in high-endemic
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Figure 1.
Stepwise approach of model development.
countries. However, the predicted impact of this universal test and
treat (UTT) intervention has not been confirmed using different
models.
Methods: We developed 9 different models of the South African HIV
epidemic in a stepwise approach of increasing complexity and
realism (Figure 1). The simplest model resembles the deterministic
model by Granich et al., while the most detailed model is a stochastic
microsimulation model (STDSIM), which, among others, includes
sexual networks and different HIV stages. Similar to Granich et al.,
we examined the impact and cost-effectiveness of a UTT intervention
Figure 2.
Track C Epidemiology and Prevention Science
of annual screening and immediate ART for HIV infected adults (aged
15) starting in 2012 and scaled-up to 90% coverage in 2019.
Results: The predicted impact of UTT on the HIV prevalence in
South Africa differs substantially between the simplest and most
detailed model, yet both models predict elimination of HIV (Figure
2). Surprisingly, the current ART roll-out of treatment at 5350 cells/
mL is already having such a substantial impact on incidence, that it
will drive HIV into an elimination phase at around 2050, even
without UTT. However, UTT is still cost-effective as many additional
life-years will be saved (Figure 3).
Epidemiological impact of UTT.
114
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
Figure 3. Cost, impact, and cost-effectiveness.
115
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
Conclusion: Our results confirm previous conclusions that the HIV
epidemic in South Africa can be eliminated through a strategy of
universal testing and treatment at 90% coverage. However, models
that capture more details underlying the HIV transmission dynamics
show that elimination is more likely to occur at a later point in time.
Also, UTT is a cost-effective intervention, but less efficient in
reducing infection than previously predicted because the current
ART treatment policy in South Africa alone will already drive HIV into
elimination.
FRLBC01
The cost-effectiveness of treatment as prevention: analysis
of the HPTN 052 trial
R.P. Walensky1,2,3, E.L. Ross1, N. Kumarasamy4, R. Wood5,
F. Noubary1, A.D. Paltiel6, Y.M. Nakamura1, S. Godbole7,
M. Hosseinipour8, J.G. Hakim9, J. Kumwenda10, J. Makhema11,
V. Akelo12, R. Panchia13, I. Sanne14, M.C. Weinstein15, E. Losina3,16,17,
K.H. Mayer18, B. Grinsztejn19, J. Pilotto20, S. Chariyalertsak21,
B. Santos22, Y.Q. Chen23, L. Wang23, X. Li23, M. McCauley24,
T. Gamble25, E. Piwowar-Manning26, L. Cottle27, I. Hoffman28,
J. Eron28, J. Gallant26, S. Swindells29, T. Taha30, K. Nielsen-Saines31,
D. Celentano30, M. Essex15, V. Elharrar32, D. Burns32, G.R. Seage15,
M.S. Cohen28 and K.A. Freedberg1,2,16
1
Massachusetts General Hospital, Boston, United States. 2Harvard
Medical School, Boston, United States. 3Brigham & Women’s
Hospital, Boston, United States. 4Y. R. Gaitonade Center for AIDS
Research and Education, Chennai, India. 5University of Cape Town
and Desmond Tutu HIV centre, Cape Town, South Africa. 6Yale
University School of Medicine, New Haven, United States. 7National
AIDS Research Institute (NARI), Pune, India. 8UNC Project Malawi and
University of North Carolina at Chapel Hill, Lilongwe, Malawi.
9
Department of Medicine, University of Zimbabwe, Harare,
Zimbabwe. 10College of Medicine Johns Hopkins Project, Blantyre,
Malawi. 11Botswana Harvard AIDS Institute, Gaborone, Botswana.
12
KEMRI-CDC Research and Public Health Collaboration, Kisumu,
Kenya. 13Perinatal HIV Research Unit (PHRU)University of the
Witwatersrand, Johannesburg, South Africa. 14University of
Witswatersrand, Department of Medicine, Johannesburg, South
Africa. 15Harvard School of Public Health, Boston, United States.
16
Boston University School of Public Health, Boston, United States.
17
Harvard Center for AIDS Research, Boston, United States. 18Fenway
Institute, Boston, United States. 19Instituto de Pesquisa Clinica
Evandro Chagas, Fiocruz, Rio de Janeiro, Brazil. 20Hospital Geral de
Nova Iguacu and Laboratorio de AIDS e Imunologia Molecular-IOC/
Fiocruz, Rio de Janeiro, Brazil. 21Research Institute for Health
SciencesChiang Mai University, Chiang Mai, Thailand. 22Hospital
Nossa Senhora da Conceição, Porto Alegre, Brazil. 23Vaccine and
Infectious Disease Division, Fred Hutchinson Cancer Research Center,
Seattle, United States. 24FHI 360, Washington, United States. 25FHI
360, Durham, United States. 26Johns Hopkins School of Medicine,
Baltimore, United States. 27Statistical Center for HIV/AIDS Research &
Prevention (SCHARP), Seattle, United States. 28University of North
Carolina at Chapel Hill, School of Medicine, Chapel Hill, United
States. 29University of Nebraska Medical Center, Omaha, United
States. 30Johns Hopkins Bloomberg School of Public Health,
Baltimore, United States. 31David Geffen School of Medicine,
University of California, Los Angeles, Division of Infectious Diseases,
Los Angeles, United States. 32National Institute of Allergy and
Infectious DiseasesNational Institutes of Health, Bethesda
United States
Presenting author email: kfreedberg@partners.org
Background: HPTN 052, a multi-country randomized trial,
showed that early ART initiation produced a 96% reduction in
HIV transmission among serodiscordant couples. Using an HIV
Table 1. Cost-effectiveness of early vs. delayed ART
Initially-infected cohort
New transmissions
Costs
Survival
Life expectancy
(2011
Transmissions/index
LMs lost due to
Cost increase due
Overall ICER
(%)
(months)
USD)
case (A%)
transmissions
transmissions
(S/YLS)
Delayed ART
84
52*
4,400
0.05 ( )
0.10
80
Early ART
93
55*
4,600
0.02 ( 59%)
0.03
30
700
Delayed ART
162
16,100
0.14 ( )
7.19
1,180
Early ART
India
184
18,400
0.15 (6%)
4.48
1,190
1,200
South Africa
5-rear Horizon
Lifetime Horizon
5-rear Horizon
52*
1,700
0.04 ( )
0.07
30
94
55*
1,700
0.02 ( 57%)
0.02
10
2,900
177
193
9,400
11,300
0.14 ( )
0.15 (3%)
5.41
3.6?
980
730
1,300
Delayed ART
Early ART
Lifetime Horizon
Delayed ART
Early ART
Cost, clinical impact, and cost-effectiveness of early and delayed ART initiation strategies. All cost and life expectancy results are presented
per initially-infected patient; values are discounted at a rate of 3% annually.
*Life expectancy at a 5-year horizon indicates the average length of survival through 5 years.
LMs, life months; ICER, incremental cost-effectiveness ratio; YLS, vears of life saved.
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
Figure 3. Cost components in RSA and India.
microsimulation model (CEPAC-International), we project the clinical
impact, costs, and cost-effectiveness of early ART.
Methods: Per the 052 protocol, we compare two ART initiation
strategiesearly (at presentation-to-care) vs. delayed (CD4 B250/ml).
Each strategy is modeled in South Africa (RSA) and India using trialderived datamean age 33.8y, mean CD4 449/ml (9120/mL), 42%
(RSA) and 67% (India) male, 0.103/1.483 transmissions/100PY while
virologically suppressed/unsuppressed. ART strategies are applied
consistently to transmitted and index cases. Outcomes includefirstorder HIV transmissions, survival, costs, and cost-effectiveness. We
designate early ART very cost-effective or cost-effective if its costeffectiveness ratio isB1x orB3x per capita GDP (GDPs$8,100 [RSA];
$1,400 [India]).
Results: In RSA, early ART increases survival, prevents costly OIs
(partially offsetting ART costs), averts early transmissions, and is very
cost-effective over both 5-year ($700/YLS, Table) and lifetime
horizons ($1,200/YLS, Table). In India over a 5-year horizon, early
ART increases survival and averts transmissions. Because ART is
expensive relative to other medical treatment in India (Figure), OI
prevention offsets fewer ART costs. Early ART, however, is costeffective ($2,900/YLS, Table); over a lifetime horizon, it becomes
very cost-effective ($1,300/YLS, Table). In sensitivity analyses in
both countries, early ART remains very cost-effective over a
lifetime horizon under a wide range of assumptions regarding
the clinical and preventive efficacy of ART. Consideration of
second-order transmissions increases the clinical and cost benefits
of early ART.
Conclusion: Early ART averts HIV transmissions over shorter horizons,
but increased survival attenuates this affect over time. Over 5 years,
early ART is cost-effective in India and very cost-effective in RSA; in
both countries, early ART is very cost-effective over a lifetime
horizon.
MOPDC0101
The effects of different ART eligibility strategies on HIVrelated morality and incidence
J. Stover and C. Pretorius
Futures Institute, Glastonbury, United States
Presenting author email: jstover@futuresinstitute.org
Background: Recent studies have demonstrated large effects of ART
in reducing HIV transmission. This study builds on these findings to
examine the impact and cost of alternative treatment strategies in a
variety of epidemic settings.
Methods: We developed a model that tracks the HIVadult
population by CD count and estimates new HIV infections as a
function of the current force of infection modified by changes in the
CD4 count distribution of the HIVpopulation and the proportion
on ART. We applied the model to eight countries in Sub-Saharan
Africa.
We used the model to evaluate several treatment strategiesscaling
up coverage to 80% with eligibility at B350, adding pregnant
women B500, adding pregnant women 500, adding sero-discordant couples B500, adding 80% of those B500, and adding 80%
of 500. We modeled a range of costs per patient from constant to
declining according to the goals of the Treatment 2.0 initiative.
Results: Figure 1 shows that each addition to the eligible population
contributes to averting additional infections. Cost per infection
averted ranges from $3600 to $11,000, Table 1. It is lowest for
expanding treatment to all those with CD4 counts below 350,
intermediate when treatment is expanded to 350500, and highest
for strategies that include treating people with CD4 counts 500.
The number of years of treatment per infection averted (Figure 2)
varies from a low of 3.3 (B350 in Uganda) to a high of 20 (treating
pregnant women 500 in South Africa).
Conclusion: Expanding treatment coverage can make a significant
contribution to prevention efforts and will be cost-effective in most
Table 1.
Incremental Cost per Infection Averted
Constant Cost Declining Cost
per Patient
per Patient
ART for 80%B350
$5,200
$3,600
Plus HIVPregnant Women B500
Plus HIVPregnant Women 500
$5,700
$8,700
$4,200
$5,100
Plus Sero-Discordant CouplesB500
$9,600
$4,200
Plus 80%B500
$7,800
$4,400
Plus 80%500
$10,900
$5,800
117
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
MOPDC0103
Modelling potential preventive impact of expanded
antiretroviral therapy, early antiretroviral therapy for
serodiscordant couples and harm reduction interventions in
a concentrated epidemic in Viet Nam
M. Kato1, R. Granich2, H. Tran Vu3, P. Nadol4, K. Sabin1, A. Suthar2 and
B. Williams5
1
World Health OrganizationViet Nam Country Office, Hanoi, Viet
Nam. 2HIV Department, World Health Organization, Geneva,
Switzerland. 3Partners in Health Research, Hanoi, Viet Nam. 4Center
for Disease Control and PreventionViet Nam Country Office, Hanoi,
Viet Nam. 5South African Centre for Epidemiological Modelling and
Analysis (SACEMA), Geneva, Switzerland
Presenting author email: katom@wpro.who.int
Figure 1.
Infections Averted, 20122025.
settings if costs per patient continue to decline. Results are most
sensitive to assumptions about the effects of ART in reducing
infectiousness in national programs and future reductions in costs
per patient.
Background: Few studies have examined the preventive effect of
expanding antiretroviral therapy (ART) in Asian epidemics. Viet Nam
has a concentrated epidemic with the highest HIV prevalence
observed in people who inject drugs (PWID). Viet Nam aims to
maximize the survival and preventive benefits of ART and plans an
operational provincial pilot. Optimal targets and strategy need to be
identified to achieve the goal.
Methods: We constructed a mathematical model (deterministic
transmission model) to explore the effects of expansion of ART, early
ART for serodiscordant couples irrespective of CD4 count and harm
reduction interventions on the concentrated epidemic in Viet Nam.
HIV prevalence trends and population size of PWID, female sex
workers (FSWs) and their male clients, men having sex with men
(MSM) and low risk women in Can Tho province, Viet Nam, were
used in the model.
Results: Compared to the current ART scenario (50% coverage, CD4
at ART initiation at 100 cells/mm3), achieving 80% ART coverage at
CD4 threshold at 350 cells/mm3 will lead to approximately 20%
reduction in new HIV infection annually, and biannual testing and
immediate ART with 80% coverage will lead to 38% reduction. Early
ART for serodiscordant couples potentially reduces annual HIV
incidence in low risk women over 40% if high coverage is achieved.
Opioid substitution therapy (OST) and needle syringe program (NSP)
for PWID will reduce new infection in all the subpopulations.
Conclusion: Our modelling suggests that ART, combined with NSP
and OST for PWID, could have a major impact on Viet Nam’s HIV
epidemic. National programs should consider further expansion of
ART and earlier ART initiation to enhance ART’s preventive impact.
It is essential to address access barriers for key affected populations
(e.g. discrimination, punitive policies) and to employ approaches that
respect people’s rights during this expansion.
MOPDC0106
Sustained treatment as prevention: continued decreases in
unprotected sex and increases in virological suppression
after HAART initiation among participants in HPTN 052
Figure 2.
Person-Years of ART per Infection Averted.
K. Mayer1, L. Wang2, I. Hoffman3, M. McCauley4, X. Li2, S. Safren5,
T. Gamble4, J. Talley4, L. Cottle6, E. Piwowar-Manning7, V. Akelo8,
S. Badal-Faesen9, N. Chotirosniramit10, N.M. Fernandes11,
N. Kumarasamy12, S. Sahay13, J. Makhema14, B. Panchia15,
J.H.d.S. Pilotto16, B.R. Santos17 and M.S. Cohen18
1
Fenway Community Health, Boston, United States. 2Vaccine and
Infectious Disease Division, Fred Hutchinson Cancer Research Center,
Seattle, United States. 3Department of Medicine, University of North
Carolina-Chapel Hill, Chapel Hill, United States. 4FHI 360, Washington,
United States. 5Harvard Medical School/Massachusetts General
Hospital and Fenway Health, Boston, United States. 6Statistical
118
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
suppressed, compared with 22% of D participants. Self-reported
unprotected anal intercourse was uncommon ( B0.3% at baseline,
and no change over time). Only 21% of participants on HAART who
engaged in UVI or UAI had detectable plasma viremia.
Conclusion: Participants randomized to early HAART and those
who subsequently initiated HAART did not increase risk taking
over several years. The decrease in sexual risk taking, coupled
with effective virologic suppression, suggest that earlier initiation
of HAART could have sustained effects in decreasing HIV
transmission.
Center for HIV/AIDS Research & Prevention (SCHARP), Seattle,
United States. 7Pathology Department, Johns Hopkins University
School of Medicine, Baltimore, United States. 8Kenya Medical
Research Institute Center for Global Health Research, Kisumu, Kenya.
9
University of the WitwatersrandClinical HIV Research Unit,
Johannesburg, South Africa. 10Chiang Mai UniversityResearch
Institute for Health Sciences, Chiang Mai, Thailand. 11Instituto de
Pesquisa Clinica Evandro Chagas, Rio de Janeiro, Brazil. 12YRG CARE
Medical Centre, VHS, Chennai, India. 13National AIDS Research
Institute (ICMR), Pune, India. 14Botswana Harvard AIDS Institute,
Gabarone, Botswana. 15University of the Witwatersrand, Perinatal
HIV Research Unit, Johannesburg, South Africa. 16Hospital Geral de
Nova Iguacu and Laboratorio de AIDS e Imunologia Molecular-IOC/
Fiocruz, Rio de Janeiro, Brazil. 17Hospital Nossa Senhora da
Conceição, Porto Alegre, Brazil. 18Department of Medicine,
University of North Carolina School of Medicine, Chapel Hill,
United States
Presenting author email: kmayer@fenwayhealth.org
C35 - Behavioural surveillance
MOPDC0205
Sexual behaviour trends by gender in a rural South African
population-based cohort during the era of scaled-up access
to VCT and ART, 20052010
Background: HPTN 052 demonstrated a 96% decrease in HIV
transmission when infected persons in serodiscordant relationships
initiated HAART at study entry compared to those randomized to
delayed treatment. However, this benefit could be attenuated if HIVinfected participants subsequently increased unprotected sex without virological control.
Methods: Between 06/2007 and 05/2010, 1763 HIV serodiscordant
couples were enrolled in 9 countries in Africa, Asia and the Americas,
and followed for a median of 2 years. The current analyses compared
the sexual behavior of HIV-infected participants before and after they
initiated HAART, and examined trends to evaluate whether risk
taking changed over time by GEE models.
Results: At enrollment, 4.0% of HIV-infected participants in the early
treatment group (E) and 5.7% in the delayed arm (D) self-reported
unprotected vaginal intercourse (UVI) with their primary partner
within the past week. At 3 months, 2.9% of E participants did,
compared to 3.0% of D participants (p 0.9). Over 2 years, UVI
decreased among all participants ( 0.015, p0.04), and the
time trend was similar in both arms. Participants engaging in UVI
were more likely to be female (AOR 1.6, 95%CI 1.12.4), from
South America vs. Asia, AOR16.0, 95%CI 8.231.3), from Africa vs.
Asia(AOR8.8, 95%CI 5.015.6), use substances (AOR 2.2,95% CI
1.33.9), and have a lower viral load at enrollment (AOR 0.7, 95%
CI 0.60.9). After 2 years, 91% of E participants were virologically
N. McGrath1,2, J.W. Eaton3, F. Tanser1, T. Bärnighausen1,4 and M.L. Newell1,5
1
Africa Centre for Health and Population Studies, University of
KwaZulu-Natal, Mtubatuba, South Africa. 2London School of Hygiene
and Tropical Medicine, London, Infectious Disease Epidemiology,
London, United Kingdom. 3Imperial College, London, Infectious
Disease Epidemiology, London, United Kingdom. 4Harvard School of
Public Health, Global Health and Population, Boston, United States.
5
Institute of Child Health, University College London (UCL), Centre for
Paediatric Epidemiology and Biostatistics, London, United Kingdom
Presenting author email: nuala.mcgrath@lshtm.ac.uk
Background: In rural KwaZulu-Natal, HIV incidence has been high and
changed little even while HIV testing uptake has increased dramatically over the past six years. We examine population-level trends in
sexual risk behavior over the period 20052010 in a generalpopulation cohort.
Methods: We report trends in sexual behaviour indicators from 2005
to 2010 for men and women aged 1749, based on annual sexual
behavior surveys collected by the Africa Centre Demographic
Information System (ACDIS). Indicators include the proportion ever
had sex, the average number of sexual partners in the past year, the
Table A. Survey participation and knowledge of HIV status
2002
Number of residents
2006
2007
2008
2009
2010
Men
Women
Men
Women
Men
Women
Men
Women
Men
Women
Men
Women
10240
13667
10152
13574
10452
14133
10508
14217
10433
13964
11084
14856
aged 1749
Number of survey
4339
participants (%)
Number with
complete sexual
7413
4091
6903
2698
5433
2370
4367
2499
5437
2780
5485
(54%)
(40%)
(51%)
(26%)
(38%)
(23%)
(31%)
(24%)
(39%)
(25%)
(37%)
(42%)
3881
6559
3672
6339
2513
5019
2047
3999
1507
3404
1790
3319
(89%)
(88%)
(90%)
(92%)
(93%)
(92%)
(63%)
(92%)
(60%)
(63%)
(64%)
(61%)
26%
45%
26%
51%
28%
59%
46%
74%
51%
77%
behaviour data (%)
Unadjusted % knows
HIV status (95% CI)
Adjusted % knows HIV
status (95K CI)
(2427)% (4447) (2528) (5053) (2630) (5760) (4448) (7275) (4953) (7678)
29%
(2730)
47%
30%
53%
33%
61%
49%
74%
52%
78%
(4548) (2832) (5255) (3035) (5962) (4651) (7376) (5054) (7679)
119
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Figure 1.
Track C Epidemiology and Prevention Science
Person-Years of ART per Infection Avertd.
point-prevalence of concurrent sexual partnerships, and condom use
at last sex with regular and casual partners. Trends are compared
between groups defined by HIV status, knowledge of HIV status, and
by other population characteristics.
Unadjusted trends and trends adjusted for varying survey participation (A) are presented.
Missing data in completed surveys is adjusted for using multiple
imputation incorporating demographic, socioeconomic, behavioural
and health variables from the ACDIS. Responses are weighted
by sex/age/education/location strata to adjust for survey nonparticipation.
Results: Reported sexual risk behaviours may have declined in men
and women over 20052010, but the decline is less pronounced
than would have appeared without adjusting for missing data and
survey participation (Figure A).
Increases in reported condom usage have been greater than
reductions in numbers of sexual partners. For both sexes, reported
condom usage with regular partners increases more amongst those
who know they are HIV-positive than those who have tested HIVnegative (Figure B).
Conclusion: These population trends in self-reported sexual
behaviour suggest that some behaviour change occurred between
2005-2010 in the general population. Changes occurred in both those
living with and without HIV, but the data suggest that greater changes
occurred in those who reported knowing they were HIV positive. The
full presentation will also include results of sub-group analyses.
120
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
C36 - Surveillance of HIV drug resistance
MOAC0303
The World Health Organization’s HIV drug resistance early
warning indicators: results from 50 countries 20042009
D.E. Bennett1, M.R. Jordan2,3, S. Bertagnolio2, S.Y. Hong3, G. Ravasi4,
J.H. McMahon3,5 and K.F. Kelley6
1
US Centers for Disease Control & Prevention, CGH DGHA, Atlanta,
United States. 2Department of HIV/AIDS, World Health Organization,
Geneva, Switzerland. 3Tufts University School of Medicine, Boston,
United States. 4Pan American Health Organization, Brasilia, Brazil.
5
Department of Infectious Disease, Alfred Hospital, Melbourne,
Australia. 6U.S.President’s Emergency Plan for AIDS Relief,
New Delhi, India
Presenting author email: dib1@cdc.gov
Background: The World Health Organizations HIV drug resistance
(HIVDR) Early Warning Indicators (EWIs) monitor clinic factors
associated with HIVDR. For this analysis, we selected three EWIs
strongly associated with risk factors for HIVDR monitored in 21, 28,
and 6 countries respectively in 20042009.
The first EWI monitors antiretroviral drug (ARV) pick-ups and
ascertains if they are on-time or late. The second monitors ARV
supply continuity at clinic pharmacies, monitoring whether stockouts occur of routinely-used ARV annually. The third monitors
whether HIV RNA (VL) is suppressed in cohorts of patients 12
months after ARV start. Targets were, respectively, 90% of patients
picking up ARV on-time, 100% ARV supply continuity at clinics,
and70% of patients with suppressed VL.
Methods: Results were analyzed by all countries. The total number of
clinics meeting the target in countries in each year was summed and
two-sided 95% exact binomial confidence were calculated using SAS
version 9.2 (SAS Institute, Cary, NC).
Results: On-time ARV pick-upsof 354 clinics in 21 countries,17.0%
(95% confidence intervals [CI] 13.021.1) met the target. ARV supply
continuityof 719 clinics in 28 countries 65.0% (CI:61.469.0) met the
target. VL suppressionof 46 clinics in 6 countries, 84.7% (CI:49.6
93.7) met the target.
Conclusion: EWI results identify ‘‘on-time ARV pick-up’’ as a major
challenge for patients and a potential HIVDR risk factor. Methods to
improve on-time ARV pick-up (e.g. adherence and patient tracing
interventions) and ARV supply chains may need to be prioritized
by national ARV programs to prevent HIVDR emergence. In
the reporting period, very few clinics in very few countries had
resources to monitor VL, which is an important indicator of HIVDR
development.
C40 - Monitoring and evaluation of HIV
prevention, care and treatment
MOAC0302
Effects of patient tracing on estimates of lost to follow-up,
mortality and retention in antiretroviral therapy programs
in low- and middle-income countries: a systematic review
Figure 1. Percentage of Clinics Meeting World Health Organization EWI targets in Africa, Aisa, and Latin America and the
Caribbean (LAC).
Table 1.
J. McMahon1,2, J. Elliott1,3,4, S. Hong2,5 and M. Jordan2,5
1
Alfred Hospital, Infectious Diseases Unit, Melbourne, Australia.
2
Department of Public Health and Community Medicine,
Tufts University School of Medicine, Boston, United States.
Summary estimates with and without tracing
With tracing
Outcome of
interest
Startin
Cohort (n) ART (n)
Without tracing
Rang of
Summary
estimates (%)
estimatea
LTFU
25
62791
0.315.0
Mortality
28
62791
4.229.7
Slopped ART
Transfer out
13
5
43975
6945
0.55.8
1.014.0
on ART
25
62791
58.488 5
Retention at
25
62791
47.588.5
7.691.1
Cohort (n)
Starting
Rang of
Summary
ART (n)
estimates (%)
estimatea
29
124875
0.834.8
25
113693
1.115.3
6.6 (4.39 6)
0.006
7
7
10841
6195
0.88.5
1.214.5
3.290.8
3.991.3
0.5
0.6
80.0 (76 584 5)
25
113693
58.591.0
75.8 (70.081.2)
0.04
80.0 (76 084 0)
28
113693
58.5906
72.9 (68.579.8)
0.02
10.5 (7.012.7)
2.890.2
2.7*14
15.191.7
P valueb
B0.001
Retention
original site
a
Values represent median (Q1Q3). or weighted mean9SE (estimates weighted by the inverse of their variance).
Comparing summary estimates for the 2 groups of studies (tracing and non-tracing) by Wilcoxon rank -sum test for medians or student’s t test
for weighted means.
Notes: LTFU, lost to follow up: ART, antiretroviral therapy.
b
121
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
3
Department of Medicine, Monash University, Melbourne, Australia.
Burnet InstituteCentre for Population Health, Melbourne, Australia.
5
Department of Geographic Medicine and Infectious Diseases, Tufts
Medical Center, Boston, Australia
4
Background: Lost to follow-up (LTFU) of patients receiving antiretroviral therapy (ART) programs in low-middle income countries
(LMICs) is an important driver of clinical outcomes. Physical tracing
to re-engage patients is increasingly common yet data describing
the impact of this activity on LTFU, mortality and retention are
limited.
Methods: We systematically searched for studies in LMIC programmatic settings via MEDLINE (2003-2011) and abstracts from HIV
conferences (2009-2011). Included studies reported the proportion
LTFU 12-months after initiation and tracing activities were determined from the studies or contacting study authors. Studies were
classified as tracing studies if physical tracing was available for the
majority of patients. Summary estimates from the 2 groups of
studies (tracing and non-tracing) for LTFU, died, stopped, transferred
out, and retained on ART were determined. These were medians and
interquartile range if estimates were non-normally distributed, or
weighted mean if normally distributed with weighting of each
proportion by the inverse of its variance. Summary estimates were
compared by Student’s t-test, or Wilcoxon rank-sum test as
appropriate.
Results: 261 papers and 616 abstracts were identified of which 39
studies comprising 54 separate cohorts (n 187,666) met inclusion
criteria. Treatment programs with tracing activities had lower
estimated LTFU (7.6% vs. 15.1%; p B .001) and higher estimated
mortality (10.5% vs. 6.6%; p.006), retention on ART (80.0 vs.
75.8%; p.04) and retention at original site (80.0% vs. 72.9%;
p.02) (Table).
Conclusion: Key indicators of HIV program success in LMICs are
associated with tracing activities. Knowledge of patient tracing
activities is therefore critical when interpreting program outcomes
of LTFU, mortality and retention. The halving of the proportion LTFU
in programs with tracing activities was only partially explained by a
greater ascertainment of mortality and transfer, as reflected by
improved ART retention. These data suggest that tracing result in real
improvements in patient outcomes, rather than better ascertainment of negative outcomes alone.
1
Department of Medicine, Faculty of Health Sciences, University of
the Witwatersrand (WITS), Health Economics and Epidemiology
Research Office, Johannesburg, South Africa. 2Boston University,
Center for Global Health and Development, Boston, United States.
3
Department of Medicine, Faculty of Health Sciences, University of
the Witwatersrand (WITS), Clinical HIV Research Unit,
Johannnesburg, South Africa. 4Right to Care, Johannesburg, South
Africa. 5Department of Medicine, University of California, San Diego,
United States
Presenting author email: mfox@bu.edu
Background: Routine viral load monitoring of patients on antiretroviral therapy (ART) is neither affordable nor available in most
resource-limited settings. We used data from an electronic patient
management system to develop an algorithm to identify patients at
risk of viral failure using a combination of accessible and inexpensive
markers.
MOAC0304
CD4 criteria improves the sensitivity of a clinical
algorithm developed to identify viral failure in
HIV-positive patients on first-line antiretroviral
therapy
D.H. Evans1, M. Maskew1, M. Fox2, L. McNamara1, P. MacPhail3,4,
C. Mathews5 and I. Sanne3,4
Risk score*
OR (95% CI)
p value
]6 vs.B6
1.79 (1.092.95)
0.022
]5 vs.B5
1.56 (1.102.21)
0.014
]4 vs.B4
1.34 (1.051.71)
0.019
]3 vs.B3
]2 vs.B2
1.25 (1.031.51)
1.61 (1.311.98)
0.025
B0.0001
]1 vs.B1
1.43 (1.051.96)
0.025
Figure 1. Kaplan Meier curves and log-rank tests for time to viral
failure using the predictor risk score (A) or risk category (B) [Time
to viral failure by risk score and category.
Risk category**
OR (95% CI)
p value
Low
2.12 (1.602.80)
B0.0001
Medium
4.37 (3.195.97)
B0.0001
High
10.7 (6.5817.4)
B0.0001
ROC C sttistic * 0.63; ** 0.59; CD4 criteria included in these results.
Odds ratio estimates of viral failure.
122
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Methods: We analyzed data from HIV-positive adults initiated on
ART at Themba Lethu Clinic, South Africa between April 2004
February 2010. Viral failure was defined as 2 or more consecutive
HIV-RNA viral loads 400copies/ml following suppression below
5400copies/ml. We used Cox-proportional hazards models to
calculate hazard ratios (HR) and 95% confidence intervals (CI).
Weights for each predictor associated with viral failure were created
as the natural logarithm of the adjusted HR and categorized into
low, medium and high risk groups. We assessed the diagnostic
accuracy of predictor scores and risk categories, with and without
CD4 criteria (CD4 B100cells/mm3; CD4 Bbaseline CD4; drop in
CD430%), using sensitivity, specificity, positive and negative
predictive value.
Results: Of 7369 patients, 922 (12.5%) experienced viral failure at a
rate of 39.7/100 person-years. In our model for predictor scores,
the following each received a weight of 1baseline or current
CD4B100cells/mm3, baseline WHO stage III/IV, albumin B25g/L,
diastolic blood pressureB 70mmHg, MCV B100fL, worsening WHO
stage, suboptimal adherence and new condition/symptom.
Odds ratio estimates and Kaplan Meier curves showed discrimination
of viral failure by risk score or risk category (Table 1; Figure 1).
However, the sensitivity/specificity of the risk score (]4 vs.B4) or
risk category (medium vs low/no risk) with CD4 criteria was 24.4%/
88.6% and 21.1%/89.4%, respectively. The sensitivity/specificity
without CD4 criteria was 12.3%/95.8% and 11.8%/95.9%, respectively.
Conclusion: The algorithm may be a feasible and useful screening
tool for resource-limited settings to identify patients at risk of
treatment failure allowing more frequent monitoring or targeting for
laboratory testing.
MOAC0305
Retention and risk factors for attrition among adults in
antiretroviral treatment (ART) programs in Tanzania,
Uganda and Zambia
Figure 1.
Track C Epidemiology and Prevention Science
O. Koole1, S. Tsui2, F. Wabwire-Mangen3, G. Kwesigabo4, J. Menten1,
M. Mulenga5, A. Auld6, S. Agolory6, Y.D. Mukadi7, R. Colebunders1,
D.R. Bangsberg8, E. Van Praag9, K. Torpey10, S. Williams6, J. Kaplan6,
A. Zee6 and J. Denison11
1
Institute of Tropical Medicine, Clinical Sciences, Antwerp, Belgium.
2
FHI 360, Behavioral and Social Sciences, Durham, United States.
3
Infectious Diseases Institute, Makerere University College of Health
Sciences, Kampala, Uganda. 4Muhimbili University of Health and
Allied Sciences, Dar es Salaam, United Republic of Tanzania. 5Tropical
Diseases Research Centre, Ndola, Zambia. 6Centers for Disease
Control and Prevention, Division of Global AIDS, Atlanta,
United States. 7Formerly FHI 360, Washington, United States.
8
Massachusetts General Hospital, Boston, United States. 9FHI 360,
Dar es Salaam, United Republic of Tanzania. 10FHI 360, Lagos, Nigeria.
11
FHI 360, Behavioral and Social Sciences, Washington, United States
Presenting author email: okoole@itg.be
Background: Patient retention in antiretroviral therapy (ART) care is
a major challenge in sub-Saharan Africa and a key indicator of
program quality. We assessed ART retention and predictors of
attrition (death or loss to follow-up) in ART clinics in Tanzania,
Uganda and Zambia.
Methods: We conducted a retrospective cohort study among adults
( ]18 years) starting ART during 20042010. Eighteen health
facilities, six per country, were purposefully selected. At each facility,
250 adult patients were randomly selected for inclusion. Patients
who visited clinics at least once during the 90 days before data
abstraction were defined as retained. Data on individual-and
program-level risk factors for attrition were obtained through chart
review and clinic manager interviews. Kaplan-Meier curves for
retention across study sites were created. Predictors of attrition
were assessed using a multi-variable Cox-proportional hazards
model, adjusted for site-level clustering. Missing data were handled
using the missing indicator method.
Results: From 17 facilities, 4,147 patients were included. The
retention proportion ranged from 52.0% to 96.2% at one year, from
39.7% to 93.8% at 2 years, from 32.7 to 90.4% at 3 years, and from
25.8% to 90.4% at 4 years (Figure 1).
Proportion of patients retained in the ART program.
123
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
Adjusted Hazard Ratio (95% CI)
P-value
Age at start ART (/10 years)
0.91 (0.86, 0.97)
0.004
Male gender
1.28 (1.14, 1.43)
B0.001
Year of ART initiation since the start of ART program (/year)
1.13 (1.08, 1.19)
B0.001
WHO stage III at start ART (reference: stage I & II)
1.09 (0.94, 1.28)
B0.001
WHO stage IV at start ART (reference: stage I & II)
1.59 (1.32, 1.92)
Loss of 10% bodyweight
1.21 (1.03, 1.41)
CD4 cell count (log cells/ml)
0.82 (0.73, 0.93)
0.003
Functional status: ambulatory (reference: working/active)
Functional status: bedridden (reference: working/active)
1.52 (1.30, 1.77)
2.10 (1.59, 2.77)
B0.001
0.022
Patient baseline characteristics.
Total
Number of facilities
Number of patients
17
4147
Adjusted Hazard Ratio (95% CI)
ARV drug dispensing
P-value
0.006
in community
No
12
2942
1
Yes
5
1205
0.38 (0.21, 0.68)
Program characteristics.
Preliminary multivariate analysis (Table 1 and Table 2) of characteristics at ART initiation showed that younger age, male sex, higher
WHO stage, loss 10% of bodyweight, lower CD4 cell count, poor
functional status, and later calendar year of ART initiation, were
independent risk factors for higher attrition. Sites offering ART
dispensing in the community had significantly less attrition than
those offering ART only in clinics.
Conclusion: In countries studied, patient retention to ART care
worsened over time especially among certain groups. Key interventions for males, younger persons and those with poor clinical
indicators are necessary. Increased use of community outlets for
ART drug dispensing could improve retention.
FRLBC02
HIV clinical and program outcomes among older patients
with HIV enrolled in HIV care and initiating ART in subSaharan Africa
younger (1549 years) adults. We assessed baseline differences
using descriptive statistics, retention using Cox models, and CD4
response after ART initiation with repeated-measures regression.
Adjustments made for country, facility type & location, ART initiation
year, sex, and baseline CD4 cell count (for CD4 response).
Results: 392,159 adults ]15 years enrolled in HIV care, of whom
38,341 (10%) were ]50 years; and 179,894 initiated ART, 20,337
(11%) of whom were ]50 years. Compared to 1549 year olds,
older patients were more likely to be male (50% vs. 32%, pB.0001),
and have lower CD4 count at enrollment into care (median cells/
mm3 224 vs. 263, pB.0001) but similar (though statistically
different) CD4 at ART initiation (163 vs. 157, p B.0001). Older
adults had higher mortality than younger adults one year after
enrollment (HRadj 1.27, 95% CI:1.191.35) and ART initiation
(HRadj 1.13, 95% CI:1.051.22), but lower loss to follow-up (one
year after enrollmentHRadj 0.76, 95% CI0.720.79; after ART
initiation HRadj 0.80, 95% CI0.750.84). Among 92,467 (51%) ART
M.R. Lamb1, E. Eduardo2, S. Kandula1, A. Howard1,2, W. El Sadr1,2,3,
V. Mugisha4, D. Kimanga5, B. Kilama6 and B. Elul1,2
1
Mailman School of Public Health, Columbia University, ICAP
New York, United States. 2Mailman School of Public Health, Columbia
University, Epidemiology, New York, United States. 3Columbia
University College of Physicians & Surgeons, New York, United States.
4
ICAP-Rwanda, Kigali, Rwanda. 5National AIDS and STI Control
Programme, Nairobi, Kenya. 6National AIDS Control Programme, Dar
es Salaam, United Republic of Tanzania
Presenting author email: mrl2013@columbia.edu
Background: HIV disease outcomes in older PLWH are inferior in
developed countries, but limited data are available from resourcelimited settings.
Methods: We used routinely-collected data on adults enrolled in HIV
care from 01/0512/10 at 199 clinics supported by ICAP-Columbia
University in Kenya, Mozambique, Rwanda, & Tanzania to compare
baseline characteristics and outcomes of older ( 50 years) and
Figure 1. Proportion of newly enrolling and active adult patients
who are ]50 years of age, 20052010.
124
Baseline immunologic characteristics
Enrolling into HIV care
Initiating ART
P-value
Study Population
Overall
Total Population (% of
total)
Percent male
Median (IQR) CD4 cell
50 years and older
1549 years
392,159 (100%)
38,341 (10%)
353,818 (90%)
33%
50%
32%
P-value
for difference
Overall
50 years and older
179,894 (100%)
20,337 (11%)
50%
1549 years
for difference
159,557 (89%)
B.0001
36%
34%
B.0001
Overall 259 (117460) (49%) 224 (109400) (47%) 263 (118466) (50%)
B.0001
158 (75240) (33%) 163 (88242) (33%)
157 (74240) (33%)
B.0001
Male
216 (89401) (48%) 204 (95376) (46%) 218 (88406) (48%)
Female 283 (134488) (50%) 245 (126425) (47%) 286 (135493) (50%)
B.0001
B.0001
144 (61226) (32%) 151 (77231) (32%) 140 (59225) (32%)
167 (85246) (34%) 174 (101252) (34%) 166 (83246) (34%)
B.0001
B.0001
Overall 47% (28%)
B.0001
64% (43%)
66% (41%)
63% (43%)
B.0001
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Table 1.
count at enrollment/
ART initiation (cells/
mm3) (Percent
missing CD4 count)
Percent with WHO
53% (24%)
46% (28%)
enrollment/ART
initiation (Percent
missing WHO stage)
55% (28%)
55% (25%)
55% (29%)
0.25
70% (43%)
67% (41%)
70% (44%)
B.0001
Female 43% (28%)
Male
51% (23%)
42% (28%)
B.0001
60% (43%)
64% (40%)
60% (43%)
B.0001
125
Track C Epidemiology and Prevention Science
stage III or IV at
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Figure 2.
Track C Epidemiology and Prevention Science
Median CD4 increase after ART initition.
patients with both baseline and follow-up CD4 counts, average 12month CD4 count for older adults was 15.9 cells/mm3 lower
than for younger adults (p0.006) after adjustment for variables
above.
Conclusion: About 10% of patients enrolling in care and initiating
ART in a diverse and large sample of clinics in four sub-Saharan Africa
countries were ]50 years. Compared to younger adults, older adults
were significantly more likely to be male, experience less LTF, but
have higher mortality and smaller CD4 count response after ART
initiation.
MOPDC0301
The United Kingdom’s National Health Service (NHS)
provides excellent access to high quality HIV care: results
from a national cohort
V. Delpech, Z. Yin, M. Kall and A. Brown
Heatlh Protection Agency, London, United Kingdom
Presenting author email: valerie.delpech@hpa.org.uk
Background: Early diagnosis of HIV and prompt access to antiretroviral therapy (ART) are critical in ensuring optimal care
for HIV patients. We produce key indicators aimed at monitoring
access, and the quality of care delivered, to adults living with HIV in
the UK.
Methods: Analyses of national surveillance data included linking
reports of newly diagnosed adults to annual surveys of adults
accessing HIV care and laboratory CD4 data. Deaths reports were
linked from the Office for National Statistics. Proportions are
presented among adults with relevant information available. Data
are rounded to the nearest 100.
Results: Late diagnosis: 6,600 were newly diagnosed in 2010, of
whom half were diagnosed late (CD4 B350 per mm3) in 2010
(heterosexual men 65%, women 58% and men who have sex with
men (MSM) 39%) and 28% had CD4 B200. Late presenters had 10fold increased risk of dying within a year compared to those
diagnosed promptly (4% vs 0.4%).
Prompt integration into care: Using the first CD4 count as a proxy,
overall 98% of 6,600 adults newly diagnosed in 2010 were integrated
into HIV care within 3 months, with little difference across exposure
groups.
Immunological response: Among 53,400 adults receiving care for
more than a year by 2010, 81% had a CD4350 regardless of ART
(heterosexual men 74%, women 82% and MSM 85%)
Viral suppression. Among 6,000 adults who started ART in 2009, 85%
remained on treatment and had undetectable viral load by 2010
(heterosexual men 84%, women 85% and MSM 89%).
Conclusion: We have developed robust measures of patient care
from routine surveillance data, enabling comparisons overtime and
between population groups. The NHS provides excellent access to
high quality HIV care regardless of patient characteristics, contrasting
with other high-income countries. Expanding testing to reduce late
diagnosis remains vital in improving the life expectancy of HIV
patients.
MOPDC0303
Linkage, retention, ART use and viral suppression in four
large cities in the United States
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
Figure 1. Percentage of estimated number of HIV-infected persons* in stages of the continuum of HIV care in four large United States cities
through December 2009 compared to national estimates; Chicago, philadelphia, Los Angles and San Francisco.
N. Benbow1, S. Scheer2, A. Wohl3, K. Brady4, A. Gagner1, A. Hughes2,
J. Tejero3, M. Eberhart4, V. Hu3, J. Sayles3 and S. Townsell1
1
Chicago Department of Public Health, Chicago, United States. 2San
Francisco Department of Public Health, San Francisco, United States.
3
Los Angeles County Department of Public Health, Los Angeles,
United States. 4Philadelphia Department of Public Health,
Philadelphia, United States
Presenting author email: n.benbow@gmail.com
Background: Successful HIV treatment involves timely linkage to
medical care, ongoing engagement in care, and adherence to
effective HIV treatment regimens. Compared to national data, large
urban areas may have significant variation in the level of successful
engagement of PLHA in care and treatment. Identification of these
differences can help reduce HIV disease transmission, morbidity and
mortality
Methods: HIV case surveillance data from Chicago, Los Angeles
County(LA), Philadelphia and San Francisco(SF) were used to
compare linkage to care ( 1 CD4 or VL test within 3 months of
diagnosis) among adults with a new HIV diagnosis in 2009. The
proportion who have accessed care ( 1 CD4/VL test in 2009) was
calculated for the estimated total HIV-infected adults, including those
unaware and those reported with HIV infection, living in 2009. City
estimates from the Medical Monitoring Project(MMP) were applied
to the number of HIV infected individuals to calculate the percentage
who were on ART, and among those on ART, the percentage virally
suppressed (most recent VL 200 copies/ml).
Results: The proportion of newly-diagnosed persons linked to
and engaged in care was significantly higher in LA and SF compared to Chicago and Philadelphia (p B.01; Figure 1). Among
HIV-infected adults, 47% in LA and 50% in SF were on ART, compared with Chicago(26%), Philadelphia(34%), and the U.S. overall(36%). In addition, viral suppression was achieved among 46%
of individuals in SF, 41% in LA, 27% in Philadelphia, and 22% in
Chicago.
Across all cities, a higher percentage of Whites compared to Blacks
who accessed care were on ART and were virally suppressed
(range91%94% vs. 83%85%) and (88%100% vs. 74%84%)
respectively.
Conclusion: Data from these cities highlight discrepancies in progress
towards universal HIV care, and help identify effective regional
interventions that promote access to care and treatment. Targeted
programs and funding are needed to ensure care and eliminate
racial/ethnic disparities.
MOPDC0304
Factors associated with achieving viral suppression among
newly diagnosed HIV/AIDS cases in the Washington, D.C.
S. Willis1, A. Castel1, A. Griffin2, T. West2, I. Shaikh2 and G. Pappas2
1
The George Washington University, Department of Epidemiology
and Biostatistics, Washington, United States. 2District of Columbia
Department of Health, HIV/AIDS, Hepatitis, STD and TB
Administration, Washington, United States
Presenting author email: sarah.willis2@dc.gov
Background: The District of Columbia Department of Health
(DCDOH) has supported HIV test and treat activities by increasing
the number of tests performed and emphasizing earlier linkage to
care. Data on the impact of these efforts on viral suppression (VS)
and continuity of care are limited. This analysis sought to identify
factors associated with VS among newly diagnosed HIV-infected
persons.
Methods: HIV-infected persons diagnosed from 20062007 were
identified in the DCDOH HIV/AIDS surveillance database. Cases with
an initial detectable viral load (VL) followed by at least one additional
VL test prior to 12/31/10 were included. VS was defined as VL B400
copies/mL. Bivariate analyses and multivariate logistic regression
were performed to detect differences between those who were VS
and those who were not. Among VS cases, Cox proportional hazards
ratios and Kaplan-Meier survival analysis were conducted to identify
predictors of VS.
Results: Of 988 newly diagnosed cases, 66% achieved VS prior to
12/31/2010. VS cases were significantly more likely to be ]50 years
of age at diagnosis (19% vs. 11%, p0.008) and in continuous care,
defined as 2 visits 3 months apart within 12 months (32% vs. 22%,
p0.002). Cases concurrently diagnosed with AIDS were also more
likely to achieve VS (73% vs. 62%, pB.0001). Multivariate logistic
regression revealed that MSM (aOR 1.62, 95% CI 1.1,2.4) were
significantly more likely to achieve VS than heterosexuals. Among
those achieving VS, survival analysis found that those 50 years of
age at diagnosis (aHR 1.44 95% CI 1.2, 1.8), those linked to care
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
within 3 months (aHR 1.35 95% CI 1.1, 1.6), and those in continuous
care (aHR 1.73 95% CI 1.5,2.1) were significantly more likely to
achieve VS.
Conclusion: These findings demonstrate the importance of earlier
linkage and continuity of care in achieving viral suppression and
highlight the need for more navigation programs targeted to HIVinfected persons.
WEPDC0202
Evaluation of a behaviour change communication
programme to reduce concurrent sexual partnerships in
Botswana
I. Halldorsdottir1, N. Taruberekera2, V. Capo-Chichi3, R. Firestone4,
L. Vu4, D. Sherard5 and R. Harrison1
1
PSI/Botswana, Gaborone, Botswana. 2PSI, Johannesburg, South
Africa. 3PSI, Research & Metrics, Coutonou, Benin. 4PSI, Research &
Metrics, Washington, United States. 5PSI, Sexual, Reproductive
Health and TB Department, Washington, United States
Presenting author email: iris.halldorsdottir@psi.co.bw
Background: The evidence linking concurrent sexual partnerships
(CP) to HIV transmission prompted the Government of Botswana to
launch a National Campaign in 2009 to reduce CP. The campaign
aimed to increase risk perceptions associated with concurrent
partnerships and to reduce CP.
Methods: This study tested whether exposure to campaign messages
among targeted adults aged 1835 (a) reduced concurrent partnerships, (b) increased risk perceptions associated with CPs, and (c)
reduced behavioral factors known to be associated with CP. A
national cross-sectional survey was conducted in 2011 using a twostage cluster sampling. Individuals were randomly sampled from
households within enumeration areas (n 1237 adults). Coarsened
exact matching was used to create statistically equivalent groups of
exposed and non-exposed individuals, based on radio/TV ownership
and place of residence. Logistic regression was used on the matched
sub-sample (n 1138) to ascertain the effect of intervention
exposure, accounting for gender, education, occupation, and age.
Results: Half of the respondents were female; 90% were single; 66%
had secondary education; 26% had tertiary education; 11% reported
having CP in the past 6 months; and 69% were exposed to at least
one intervention message. Exposure to campaign messages was
associated with increased risk perceptions associated with CP
(OR 1.49;95%CI1.112.01). There was no impact of the campaign message on reducing CP. However, exposure was associated
with increased self-efficacy for condom use (OR 1.38;95%
CI 1.021.88) and HIV testing (OR 1.6; 95%CI 1.062.42). In
additional analysis, those who reported having CP were more likely
to use condoms consistently (OR 2.3; 95%CI 1.73.1).
Conclusion: We found positive impacts of the intervention on
increased risk perception and condom self-efficacy. CP is rooted in
deeply entrenched social norms and thus may require a longer
intervention period to see a reduction. The finding that CP was
associated with condom use suggests that combined intervention
messages would be more appropriate than a stand-alone CP message.
C41 - Monitoring and evaluation (other)
TUAC0205
Evaluating the use of HIV surveillance data for initiating
partner services in Houston, Texas, U.S.
Track C Epidemiology and Prevention Science
S. Chan, B. Yang, M. Wolverton and R. Arafat
City of Houston, Department of Health and Human Services,
Houston, United States
Presenting author email: shirley.chan@houstontx.gov
Background: Notifying partners about HIV exposure is an important
component of HIV prevention. CDC recommends programs should
use surveillance data and disease reporting systems to identify newly
diagnosed persons. Texas law mandates that local health departments elicit partners, notify them of possible exposure to HIV, and
offer HIV counseling and testing. In Houston, the HIV/STD Surveillance Program coordinates with HIV/STD Prevention Program to
identify persons with HIV infection and provide Partner Services (PS).
These activities can prevent the spread of disease and improve
individual health as well as the health of the community.
Methods: Using HIV surveillance data from the HIV registry, the
Houston HIV/AIDS Surveillance Program identified individuals newly
diagnosed with HIV. These patients were referred to HIV Prevention
Program to conduct Partner Services. Partners identified were
contacted by Disease Intervention Specialists and confidentially
notified of possible exposure.
Using prevention data from the STD registry, patient and partner
outcome information were generated. Numbers of patient interviews
and number of partners notified and tested were tabulated.
Results: Using the HIV surveillance data, the number of HIV positive
patients referred for PS increased from 78% in 2005 to 96% in 2008.
The percentage of providers who ‘‘opt-out’’ of health departmentbased PS has decreased from 22% to 4%.
From Prevention data, the number of patients interviewed increased
from 521 in 2005 to 1,299 in 2010. More significantly, the percentage
of partners notified has increased from 57% to 79% and the number
of partners tested increased from 74% to 92%.
Conclusion: Using HIV Surveillance data for initiating Partner Services
has proven to be an effective tool for HIV prevention activities.
However, using surveillance data to initiate PHFU should be guarded
with strict protocol to avoid inadvertent breaches in confidentiality.
MOPDC0302
Trends in antiretroviral therapy use, HIV RNA plasma viral
load and CD4 T-lymphocyte counts at death among HIVpositive persons in care in the United States, 20002008
K.N. Althoff1, K. Buchacz2, I. Hall2, J. Zhang1, D.B. Hanna1, P. Rebeiro1,
S.J. Gange1, R.D. Moore1, M. Kitahata3, K.A. Gebo1, J. Martin4,
A.C. Justice5, M. Horberg6, R.S. Hogg7, T.R. Sterling8, A. Cescon7,
M.B. Klein9, J. Thorne1, H. Crane3, M.J. Mugavero10, S. Napravnik11,
G.D. Kirk1, L.P. Jacobson1, B. Rodriguez12, J.T. Brooks2 and North
American AIDS Cohort Collaboration on Research and Design
1
Johns Hopkins University, Baltimore, United States. 2Centers for
Disease Control and Prevention (CDC), Atlanta, United States.
3
University of Washington, Seattle, United States. 4University of
California at San Francisco, San Francisco, United States. 5Yale
University and the VA Connecticut Healthcare System, New Haven,
United States. 6Mid-Atlantic Permanente Research Institute,
Rockville, United States. 7BC Centre for Excellence in HIV/AIDS and
Simon Fraser University, Vancouver, Canada. 8Vanderbilt University,
Nashville, United States. 9McGill University, Montréal, Canada.
10
University of Alabama, Birmingham, United States. 11University of
North Carolina, Chapel Hill, United States. 12Case Western Reserve
University, Cleveland, United States
Presenting author email: kalthoff@jhsph.edu
Background: The US National HIV/AIDS Strategy targets for 2015
include ‘‘improving health outcomes for people living with HIV.’’ The
objective of this study was to demonstrate the changing national
128
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
1
Pan American Health Organization/World Health Organization,
Family & Community Health, Port of Spain, Trinidad and Tobago. 2Pan
American Health Organization, HIV Caribbean Office, Port of Spain,
Trinidad and Tobago. 3Pan American Health Organization, HIV/STI
Project, HIV/AIDS, Washington, United States
Presenting author email: gebrey@gmail.com
Figure 2. Trends in suppression ( 52.7 log10 capies/mL, 5500
copies/mL) of plasma HIV viral load mid-year plasma HIV viral
loads by combiantion antiretrovial therapy (ART) status, NAACCORD, 2000 2008.
trends in HIV treatment and outcomes among adults in HIV care
using the North American AIDS Cohort Collaboration on Research
and Design (NA-ACCORD).
Methods: We analyzed data from HIV-infected adults in the NAACCORD with ]1 plasma HIV RNA viral load (HIV VL) or CD4 Tlymphocyte (CD4) count measured in an HIV clinical setting in any
calendar year from 1/1/2000 to 12/31/2008. Annual percentages of
antiretroviral therapy use (ART), suppressed HIV VL, and median age
and CD4 count at death were estimated. ?2 statistics were used to
compare percentages within a calendar year; generalized linear
models with generalized estimating equations were used for
comparison across calendar years.
Results: 45,529 HIV-infected adults received care in an NA-ACCORDparticipating US clinical cohort from 2000 to 2008. From 2000 to
2008, the percentage of participants using combination ART
increased from 73% to 83% (p B0.01). In 2008, protease inhibitorbased (37%) and non-nucleoside reverse transcriptase-based (57%)
regimens were the most commonly prescribed initial combination
ART among treatment-naı̈ve adults (p B0.01). The percentage with
suppressed HIV VL ( 52.7 log10copies/mL) increased from 46% in
2000 to 72% in 2008 (p B0.01) (Figure 1). Among 4,417 participants
who died, median age at death increased from 44 to 50 years (pB
0.01) while the CD4 count at death more than tripled to 209 cells/
mm3 (p B0.01).
Conclusion: From 20002008, increases were observed in the
percentage prescribed combination ART, the percentage who
achieved a suppressed HIV VL, and the median age and CD4 count
at death. Our data show improved control of HIV with contemporary
management in the US and the utility of NA-ACCORD for monitoring
these trends.
C42 - Evaluation of health systems’
response to HIV
TUAC0204
Is HIV mother-to-child transmission and congenital syphilis
elimination by 2015 a reality in the English Caribbean?
Y. Gebre1, N. Jack2, P. Edwards2, A. Del Riego2 and S. Caffe3
Background: The countries of the Caribbean have collectively
committed to the goal of eliminating mother-to-child transmission
of HIV and syphilis as public health problems by 2015, by improving
the quality of care for pregnant women and babies, including wider
and timelier treatment for HIV and syphilis.
Methods: Sub regional analysis of the health systems HIV response
and progress to the eliminiation initiative (EI) was conducted for
selected countries in the English Caribbean. Data on the monitoring
events ( 7 output, 5 outcome & 3 impact indicators) for the EI were
collected. 20092010 data on the HIV health sector progress
towards universal access were analysed.
Results: At the end of 2010 Jamaica, Bahamas and Trinidad & Tobago
have reported reducing congenital syphilis cases below the target
of B0.5 per 1,000 births. None of the countries reported reduced
rates of MTCT of HIV to B2%, and pediatric HIV cases B0.3 per 1,000
live births. Rates of HIV screening for pregnant women range from
93% (Belize) to 95% (Jamaica), however only 24.7%45% of pregnant
women accessed ANC at clinics in their first trimester. 76%96% of
women receiving prenatal care in the four countries studied were
screened for syphilis in 2010; coverage with ARV medication
increased from 40% of HIV-positive pregnant women in 2005 to
92% in 2010, (PB0.001). The percentage of pregnant women
diagnosed with syphilis who receive appropriate treatment range
from 50% to 100%. Pregnant women having at least one visit with a
skilled ANC attendant raised from 60% to 95%, ( PB0.001).
Conclusion: With increase quality service coverage and strengthened
commitment, it now seems feasible by 2015 to eliminate new HIV
infections and CS among children in some countries of the
Caribbean. Challenges include the continued access of ARVs, other
essential supplies and human resources.
TUPDC0104
Assessing quality of services provided by communitypreferred private providers for sexually transmitted
infections in a targeted HIV prevention program in
Maharashtra, India
R. Koul and D. Vyas
Pathfinder International/India, Pune, India
Presenting author email: rkoul@pathfinder.org
Background: Providing quality sexually transmitted infection (STI)
services acceptable and accessible to high-risk individuals like female
sex workers (FSWs) and men who have sex with men (MSM)
continues to be a challenge in India. Franchising services through
preferred private providers has significantly improved coverage;
however, data on quality of care is limited. This paper presents
results from a quality assessment of community-preferred private
providers contracted in a targeted Pathfinder International-led HIV
intervention program with more than 25,000 FSWs and 11,000 MSM
in ten districts of Maharashtra.
Methods: Pathfinder used data from a clinical quality assessment
tool implemented as part of quality assurance and supportive
supervision, completed once each quarter for every preferred
provider (March 2007 to April 2011). A composite weighted scale
was developed with a maximum score of 70 and indicators assigned
to six broad areas of assessmentaccess, clinic environment, structur-
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
al, service delivery, technical, and community involvement. A mean
aggregate quality score was computed in each area and also by type
of provider, intervention, and setting to assess levels and trends of
quality of STI care provision.
Results: Analysis of 290 clinic assessment records for a total of 227
preferred private providers showed progressively increasing trends in
all quality areas of assessment irrespective of provider, setting, and
intervention type. The average quality score increased from 39.5 in
2007 to 62 by 2011. Non-allopathic and private providers in rural
settings showed consistently lower quality scores than allopathic
and urban providers, respectively. However, the difference was not
statistically significant. An overall 1.5-fold improvement in the quality
score was observed, with scores consistently above 78% in the last
three years.
Conclusion: Through continuous supportive supervision it is possible
to ensure quality of STI care provided by private providers in HIV
interventions with FSWs and MSM.
Track C Epidemiology and Prevention Science
Conclusion: HIV prevalence among PWID in Temeke was substantially
higher than population estimates (7% males, 10% females). Low HCV
awareness and high HIV/HCV coinfection prevalence raise concerns
for accelerated HCV disease progression and future liver disease
burden in this population. Injecting and sexual risk behaviours,
undiagnosed HIV and HCV, and limited access to testing, condoms
and clean injecting equipment demand urgent scaling up of
prevention and treatment services targeting PWID in Tanzania.
C45 - Prevention of mother-to-child
transmission
THAC0103
Will your partner be attending? Involving men in the
prevention of mother-to-child transmission of HIV in
antenatal care clinics in Iringa, Tanzania
C43 - Surveillance and monitoring of HIV/
hepatitis C (HCV) co-infection
MOAC0402
A critical need to scale-up of HIV prevention and harm
reduction services for people who inject drugs in
Tanzaniaresults from a HIV and hepatitis C prevalence study
in Dar es Salaam, 2011
M. Stoové1,2, A. Bowring1, N. Luhmann3, C. Debaulieu4,
D. Stéphanie3, S. Pont4, F. Assouab3, T. Abdalla3, C. van Gemert1 and
P. Dietze1
1
Burnet Institute, Centre for Population Health, Melbourne,
Australia. 2Monash University, Epidemiology and Preventive
Medicine, Melbourne, Australia. 3Médecins du Monde, Paris, France.
4
Médecins du Monde, Dar es Salaam, United Republic of Tanzania
Presenting author email: stoove@burnet.edu.au
Background: The number of people who inject drugs (PWID) has
grown substantially in Tanzania, with increasing significance for HIV
control. We determined HIV and hepatitis C (HCV) prevalence, service
access and risk behaviours among PWID in Temeke District, Tanzania.
Methods: Researchers administered a quantitative survey alongside
rapid HIV/HCV antibody testing to PWID in Temeke. HIV, HCV and
coinfection prevalence with 95% CIs was calculated with descriptive
analyses of service access and risk behaviours.
Results: 267 PWID (87% males) reported a median injecting duration
of five years (IQR39). HIV prevalence was 34.8% (95%CI29.1
40.9); 29.9% (95%CI 24.036.2) among males and 66.7% (95%CI
49.081.4) among females. HCV prevalence was 27.7% (95%CI
22.433.5) and similar for males and females. HIV/HCV coinfection
prevalence was 16.9% (95%CI12.621.9); 15.2% (95%CI10.8
20.4) among males and 27.8% (95%CI 14.245.2) among females.
Most (73%) positive HIV tests were previously undiagnosed. Over
half PWID (53%) had no HIV testing history and 76% had not tested
in the past two years. One-third of PWID (34%) reported not knowing
where to access HIV testing. Two-thirds (66%) had not heard of HCV
and 98% had never tested for HCV.
Common sharing behaviours included injecting with a used syringe
(42%) and sharing other equipment (17%) or mixing containers
(14%). Nearly one-third (30%) of HIV positive PWID reported recent
unprotected sex. About half PWID reported having not received
condoms (52%) or clean injecting equipment (54%) in the past 12
months.
N. Kikumbih1, J. Nielsen-Bobbit2, A. Mbandi1, W. Motta1, R. Killian1
and F. Mwanga1
1
EngenderHealth, ACQUIRE Tanzania Project, Dar es SalaamUnited
Republic of Tanzania. 2EngenderHealth, Dar es Salaam, United
Republic of Tanzania
Background: HIV prevalence among Tanzanian adults is 6%; with
mother-to-child HIV transmission (MTCT) accounting for one in ten
infections. Men play a decisive role in women’s utilization of health
services, but male involvement with their partners in the prevention
of MTCT (PMTCT) program is low. To address this issue, the ACQUIRE
Project Tanzania (ATP) has supported the Ministry of Health and Social
Welfare since 2008 to involve men in antenatal care (ANC) services in
Iringa, the region with the country’s highest HIV prevalence (16%).
Interventions include partner invitation letters, posters encouraging
male attendance, prioritizing clients accompanied by partners,
improving couple counseling rooms, training providers on PMTCT
couple counseling, and engaging villages to develop local strategies.
This evaluation assesses uptake of PMTCT services by pregnant
women and their partners before and after interventions began.
Methods: A repeated cross sectional study was conducted in 354
facilities in Iringa, Tanzania between 2008 and 2011. Facility-level
data on PMTCT service uptake were collected to assess partner HIV
testing before and after male involvement interventions. Data were
analyzed using descriptive statistics.
Results: The number of ANC partners tested annually for HIV
increased from 1,746 in 2007/08 to 10,559 in 2008/09, and 20,758
in 2009/10. Prior to interventions 7% of ANC partners were tested;
after interventions 30% of partners tested in 2008/09, 40% in 2009/
10 and 50% in 2010/11. While the number of partners tested
increased the proportion testing positive decreased below the
regional rate from 16% in 2007/08 to 10% in 2010/11. Male
participation was higher in facilities with strong community support;
for example up to 80% of ANC clients at Mtwango Dispensary were
accompanied by partners consenting to test.
Conclusion: Locally initiated interventions on male involvement are
crucial for the reduction of MTCT and men can be engaged to utilize
and support PMTCT services.
THAC0104
HIV seroconversion during pregnancy and mother-to-child
HIV transmission: data from the Enhanced Perinatal
Surveillance Project, United States, 20052010
130
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Journal of the International AIDS Society 2012, 15 (Suppl 3)
S. Singh1, M.A. Lampe1, A. Surendera Babu2, S. Rao1, C.B. Borkowf1
and S.R. Nesheim1
1
Centers for Disease Control and Prevention, Division of HIV/AIDS
Prevention, Atlanta, United States. 2ICF International, Atlanta
United States
Presenting author email: fyv7@cdc.gov
Background: In the United States (US), HIV screening is recommended for all pregnant women. Repeat screening is recommended
in jurisdictions with elevated rates of HIV and for women with known
HIV risk. This study examined the numbers of women seroconverting
prior to pregnancy (PTP) and during pregnancy (DP) and the
associated mother-to-child HIV transmission (MCT).
Methods: Data from HIV-infected women who delivered live infants
from 20052010 in 15 US areas that conduct the Centers for Disease
Control and Prevention’s Enhanced Perinatal Surveillance (EPS) were
used. EPS data were linked with National HIV Surveillance data
reported through June 2011 to replace missing test dates. We
determined the number of PTP- and DP-seroconverters as well as
those who could not be classified due to missing testing data. DPseroconverters had both a documented negative HIV test followed
by a positive test during pregnancy or labor/delivery, whereas PTPseroconverters were diagnosed HIV positive before pregnancy. We
calculated the number of MCT among both seroconverter groups.
Estimated annual percent change was used to examine trends in the
percentages of DP-seroconverters as well as MCT in both seroconverter groups.
Results: Among 10,308 HIV-infected women with live births, 124
(1.2%) were DP-seroconverters, 7,235 (70.2%) were PTP-seroconverters and 2,949 (28.6%) were unclassifiable. A statistically significant
25.0% estimated annual increase in the percent of DP-seroconverters
was observed from 20052010 (95% CI12.3%39.1%). MCT occurred
among 2.0% of all deliveries; of these, MCT among DP-seroconverters (12.9%) was eight times that among PTP-seroconverters
(1.6%)(Z9.3, pB0.0001). Non-significant decreases in the percent
of MCT were observed in both DP- (p0.8) and PTP-seroconverters
(p 0.1) from 20052010.
Conclusion: From 20052010, there was a significant increase in
the percent of women seroconverting during pregnancy. Efforts for
consistent early prenatal HIV testing and repeat third-trimester
testing should be enhanced and monitored to assure universal timely
provision of MCT prophylaxis.
THAC0105
CD4 assessment among newly diagnosed HIV-positive
pregnant women in India’s national prevention of motherto-child transmission (PMTCT) programmeimplications for a
’test and treat’ approach
S.K. Mohammed1, R.S. Gupta2, R. Rao2, V. Joseph2 and P. Srikantiah3
1
Reproductive and Child Health Division, Ministry of Health and
Family Welfare, Government of India, New Delhi, India. 2National
AIDS Control Organisation, Department of AIDS Control, Ministry of
Health and Family Welfare, Government of India, New Delhi, India.
3
University of California, San Francisco, HIV/AIDS Division, San
Francisco General Hospital, San Francisco, United States
Presenting author email: sureshmohammed@gmail.com
Background: The 2010 WHO PMTCT guidelines highlight the
importance of CD4 testing for all pregnant HIV women, and
strongly recommend lifelong antiretroviral therapy (ART) for everyone with CD4 B350 cells/mm3. We examined 2009 and 2010
national data in India, where an estimated 43,000 HIV-positive
Track C Epidemiology and Prevention Science
pregnant women require PMTCT services annually, to assess CD4
testing practices and inform programme policy.
Methods: Antenatal HIV testing data were routinely collected from
HIV Integrated Counselling and Testing Centres (ICTCs). ICTC and ART
centre records in each state were abstracted to evaluate the number
and proportion of HIV-infected pregnant women who received CD4
testing, proportion with CD4 count B350 cells/mm3, and number
initiated on ART.
Results: Of 5,807,778 pregnant women tested across India in 2009,
18,692 (0.32%) were detected HIV-positive. Among HIV pregnant
women, 10,192 (54.5%) received CD4 testing, of whom 3,082 (30.2%)
had a CD4 count B350 cells/mm3. In 2010, 16,204 (0.24%) of
6,877,617 tested pregnant women were detected HIV-positive.
Among these, 9,917 (61.2%) received CD4 assessment, and 3,934
(39.7%) had a CD4 count B350 cells/mm3. In 2010, 2,292 pregnant
women started lifelong ART, representing 58% of those with
CD4B350 cells/mm3.
Conclusion: Among those tested, approximately 40% of pregnant
HIV women in India require ART for their own health. However,
almost 40% of detected women did not receive timely CD4
assessment or linkage to treatment. In light of these data, the Indian
national programme has opted to provide a single maternal triple
antiretroviral prophylaxis regimen to all HIV pregnant women,
irrespective of CD4 count. This ‘‘test and treat’’ approach can be
initiated before CD4 results are known, potentially reducing losses to
follow-up and delays in ART initiation. Expansion of CD4 assessment
remains a high priority in India, as CD4 results will still guide maternal
ART duration (lifelong vs. until cessation of breastfeeding).
TUPDC0205
Social and structural barriers to uptake of PMTCT in Nyanza
province, Kenyaa community-based survey
P. Kohler1, J. Okanda2, J. Kinuthia3, G. Olilo2, F. Odhiambo2, L. Mills4,
L. Kayla4 and G. John-Stewart5
1
University of Washington, Global Health and Nursing, Seattle,
United States. 2Kenya Medical Research Institute (KEMRI)/ Centers
for Disease Control and Prevention (CDC) Research and Public Health
Collaboration, Kisumu, Kenya. 3University of Nairobi, Kenyatta
National Hospital, Obstetrics and Gynaecology, Nairobi, Kenya.
4
Center for Disease Control and Prevention, Kisumu, Kenya.
5
University of Washington, Global Health, Medicine, Epidemiology
and Pediatrics, Seattle, United States
Presenting author email: pkohler2@uw.edu
Background: Prevention of mother-to-child transmission (PMTCT)
programs are expanding throughout Africa. It is important to define
modifiable barriers in order to improve PMTCT programs. There are
few community-based studies that sample a broad population of
mothers, including those who never access clinics.
Methods: Community-based surveys were conducted in FebruaryJune 2011 among women who delivered within the prior year under
the Kenya KEMRI-CDC Health and Demographic Surveillance System.
Rates of uptake of antenatal care (ANC), HIV testing and maternal/
infant antiretrovirals at most recent pregnancy were determined,
and barriers were identified in multivariate regression.
Results: Overall, 616/652 (95%) of women accessed ANC. Eighty-four
percent of women with negative/unknown HIV status were tested for
HIV, 89% of these at first ANC visit. Among 216 HIV-seropositive
women, 82% took antiretrovirals for PMTCT (72% antenatally, 62% at
labor, 72% postpartum, but only 55% at all three times); 79% of
infants received PMTCT antiretrovirals. Receipt of antiretrovirals
during labor was significantly associated with facility delivery (69%
131
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
facility-based vs. 55% non-facility, pB0.03). In multivariate analysis,
primary education (5.83; 1.6420.67) and fewer previous pregnancies (0.65; 0.500.85) were associated with accessing ANC. Knowing
partner was HIV-tested (4.37; 1.6211.73), believing MTCT can be
prevented (3.31; 1.219.06) and having iron roof or better (4.35;
1.1716.20) were associated with uptake of HIV testing. Among HIVpositive women, knowing partner was HIV-tested (2.39; 1.025.61)
and ANC attendance (7.81; 1.2250.02) were associated with uptake
of maternal antiretrovirals.
Conclusion: In this community-based survey, uptake of HIV testing
and antiretrovirals was relatively high. Although most HIV-infected
women received antiretrovirals, fewer received a complete course.
Education, PMTCT knowledge, and partner testing correlated with
ANC/PMTCT uptake. Our findings suggest that partner testing
initiatives may have benefit for PMTCT. Planned initiation of
universal antiretroviral therapy for pregnant women in Kenya may
improve antiretroviral coverage during labor.
Disclaimer: The content and views in this abstract are solely the
responsibility of the authors and do not necessarily represent the
official views of the affiliated organizations, United States Government, or Government of Kenya.
skills in couple counseling. Data management tools were provided
and providers were trained on completion.
Results: 2,579 pregnant women and their partners from 7 sites were
counseled and tested together between 2009 and 2011 compared to
the previous years (20052008) when none of the pregnant women
came with their spouses in the same sites. During the same period
(2009 to 2011) the number of women taking ARVs for prophylaxis
increased by 20% between 2009 and 2010. The majority of pregnant
women are now being counseled and tested together with their
partners during their first visit to the antenatal clinic.
Conclusion: Couple counseling is a good strategy to encourage ARVs
uptake by pregnant women. Health care workers should be given the
necessary knowledge and skills to address couple counseling and
testing.
C46 - Male and female condoms and
other physical barriers
WEPDC0201
Efficacy of a randomized intervention trial promoting
female condom use among female South African tertiary
students
TUPDC0206
Couple counseling increases antiretroviral (ARV) uptake by
pregnant women: a case report in Zambia Defense Force
health facilities
W. Kanjipite1, J. Nikisi2, M. Chilila3, H. Shasulwe3, J. Banda3 and
J. Mulilo4
1
Jhpiego, Monitoring and Evaluation, Lusaka, Zambia. 2Jhpiego,
Technical Department, Lusaka, Zambia. 3Jhpiego, HIV/AIDS, Lusaka,
Zambia. 4Zambia Defence Forces, Zambia National Service, Lusaka,
Zambia
Presenting author email: mchilila@jhpiego.net
Background: Zambia has established the Prevention of Mother
to Child Transmission of HIV (PMTCT) programme to reduce the
burden of vertical HIV transmission. More than 90 percent of women
attending antenatal care services (ANC) are tested for HIV, though
only 10 percent of couples in Zambia have tested for HIV together.
Encouraging couples to undergo HIV testing and counseling together
bypasses barriers associated with disclosure and facilitates adherence to ARVs.
Methods: Following the revision of the PMTCT guidelines which
strengthened recommendations for couple counseling, job aids
were provided to health care providers. Mentorship was provided
to health care workers to change their attitudes and improve their
One-Session
J.A. Smit1, S. Hoffman2, Z. Mabude1, M. Beksinska1, Z.A. Stein2,3,
C. Ngoloyi1, E.A. Kelvin2,4, T.B. Masvawure2, J. Pienaar1, C.-S. Leu2,5,
T. Exner2 and J.E. Mantell2
1
MatCH [Maternal, Adolescent and Child Health], Durban, South
Africa. 2HIV Center for Clinical and Behavioral Studies, New York
State Psychiatric Institute and Columbia University, Psychiatry,
New York, United States. 3Columbia University, G.H. Sergievsky
Center, New York, United States. 4City University of New York School
of Public Health at Hunter College, Epidemiology, New York,
United States. 5Mailman School of Public Health, Columbia
University, Biostatistics, New York, United States
Presenting author email: jsmit@match.org.za
Background: Relatively few systematic intervention studies have
tested the efficacy of female condom (FC) promotion. We compared
the efficacy of an enhanced two-session cognitive-behavioral intervention versus a single-session ’basic’ intervention to promote the FC
among female students at a South African tertiary institution.
Methods: A total of 296 women students were randomized to either
the two-session (N 147) or one-session (N 149) intervention.
Both arms received HIV/STI/pregnancy prevention information in
group settings, including information on FC use and modeling of FC
insertion. The two-session additionally covered partner negotiation,
Two-Session
Intervention Effect
Outcomenumber of vaginal intercourse occasions unprotected by either male or female condoms
Mean
b
p-value
p-value
Y
Baseline
12.68
NA
NA
Baseline
7.10
NA
NA
NA
NA
FU1
6.75
.63
.02
FU1
2.29
.90
B.0001
.27
.44
FU2
5.02
.93
B.0001
FU2
2.24
.92
B.0001
.01
.97
Mean
p-value
Outcomenumber of female condom used
Baseline
FU1
.02
2.43
NA
4.91
NA
B.0001
Baseline
FU1
.15
2.40
NA
2.82
NA
B.001
NA
2.09
NA
.06
FU2
1.04
4.06
B.0001
FU2
1.78
2.54
B.01
1.52
.18
Effects of a One vs. Two-Session FC Intervention.
132
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
FC insertion practice, and personal goal-setting to achieve HIV/
pregnancy prevention. Both groups had access to male and female
condoms. Intervention effects were assessed at 2.5 and 5 months
post-intervention. Data were analyzed using GLM, with GEE to adjust
for within-subject correlation.
Results: Both groups reported significant reductions in the number
of vaginal intercourse occasions unprotected by either male or
female condoms from baseline to the 2.5 and 5-month follow-ups.
There were no differences between groups at either time point.
Similarly, the number of FCs used increased significantly in both
groups at first and second follow-ups; differences between groups
again were non-significant at both time points.
Conclusion: These findings suggest that both interventions decreased unprotected sex and increased the number of FCs used.
The shorter, single-session group-based intervention, which could
easily be delivered in a clinic waiting room, holds promise in
resource-constrained settings. The relatively short follow-up period
Track C Epidemiology and Prevention Science
does not allow us to rule out the possibility of differential longerterm effects between groups.
C47 - Harm reduction, including
reduction of unsafe injecting and other
approaches
THAC0503
Cost-effectiveness of combined sexual and injection risk
reduction interventions among female sex workers who
inject drugs in two very distinct Mexican-U.S. border cities
CE Acceptability Curve for Ciudad Juarez.
133
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
J.L. Burgos1,2, T.L. Patterson3, J.S. Graff-Zivin4, J.G. Kahn5,
M.G. Rangel6, V.D. Ojeda1, M.R. Lozada7 and S.A. Strathdee1
1
University of California San Diego School of Medicine, Division of
Global Public Health, La Jolla, United States. 2Universidad Autonoma
de Baja California, Facultad de Medicina, Tijuana, Mexico. 3University
of California-San Diego (UCSD), Psychiatry, La Jolla, United States.
4
University of California San Diego, International Relations and Pacific
Studies, La Jolla, United States. 5University of California San Francisco
School of Medicine, San Francisco, United States. 6El Colegio de la
Frontera Norte, Estudios de Poblacion, Tijuana, Mexico. 7ISESALUD,
Programa Estatal de Prevencion y Control del VIH e ITS, Tijuana,
Mexico
Presenting author email: jlburgos@ucsd.edu
Background: We evaluated the cost-effectiveness of combined single
brief interventions (Mujer Mas Segura, MMS) to promote safer-sex
and safer-injection practices among injecting female sex workers
(FSW-IDUs) in Tijuana (TJ) and Ciudad Juarez (CJ) Mexico. Data were
from an RCT conducted between 20082010 coinciding with a period
of expansion of needle exchange (NEP) in TJ, but not in CJ.
Methods: A Markov model was developed to estimate the incremental cost per quality adjusted life years gained (QALYs) over oneyear and lifetime-time horizons among a hypothetical cohort of
1,000 FSW-IDUs comparing standard prevention strategies in Mexico
to each individual intervention component and the combined MMS
intervention. We applied a societal perspective, an annual discount
rate of 3% and currency adjusted to 2012 USD. A multivariate
sensitivity analyses was performed to explore model robustness.
Results: For CJ, over a one-year time horizon, the individual safer-sex
intervention was cost-effective at $1,510 ($80$10,080) per QALY
gained, the combined intervention was not cost-effective at more
than 3 times the Mexican GDP per capita. Over a lifetime, both the
safer-sex and combined MMS interventions were cost-effective at
$641 ($80$9,244) and $1,117 ($310$14,400) per QALY gained,
respectively. For TJ, both the safer-injection and combined MMS
interventions were not cost-effective compared to the single safersex intervention for both one-year and lifetime. However, the safersex intervention was highly cost-effective at $1,964 ($120$8,343)
and $783 ($104$9,500) per QALY gained for one-year and lifetime,
respectively.
Conclusion: In the absence of expanded NEP in CJ, the combinedMMS is highly cost-effective over a lifetime. In contrast, in TJ where
NEP expansion suggests that improved access to sterile syringes at
the community-level significantly reduced injection-related risks, the
combined MMS was effective with no significant added benefit from
the safer-injection component of MMS. Analyses taking into account
the cost of NEP expansion in TJ are pending.
C49 - Male circumcision
TUAC0401
What women think about male circumcisionperceptions of
female partners of recently circumcised men in Nyanza
province, Kenya
T. Okeyo Adipo1, N. Westercamp2, K. Agot3, W. Jaoko4 and R. Bailey2
1
Nyanza Reproductive Health Society, Kisumu, Kenya. 2University of
Illinois at Chicago, School of Public Health, Chicago, United States.
3
Impact Research and Development Organisation, Kisumu, Kenya.
4
University of Nairobi, Nairobi, Kenya
Presenting author email: timadipo@yahoo.com
Track C Epidemiology and Prevention Science
Background: As medical male circumcision services are scaled up in
sub-Saharan Africa, understanding circumcision’s impact on sexual
satisfaction, attitudes and behavior of female partners of recently
circumcised men is crucial to women’s well-being and program
success.
Methods: We conducted a longitudinal study of behavioral risk
compensation following circumcision among 1835 year-old men in
Western Kenya. Men circumcised during the study were asked to
refer their female partners to be interviewed for the study.
Results: We recruited 101 women (median age 21; IQR 1924) who
were in a relationship with the referring man before and after his
circumcision. All female participants reported being satisfied with
their partner’s decision to become circumcised and his sexual
performance after circumcision. Ninety-six percent were satisfied
with the appearance of partner’s penis and 91% reported enjoying
sex more after circumcision. Most women (84%) reported having no
or small chance of getting HIV; 38% attributed this low risk to their
partner’s new circumcision status. Eighty-eight percent felt more
protected from sexual diseases after their partners? circumcision.
Overall, women and men held similar beliefs about circumcision.
However, attitudes that could potentially lead to risk compensation
were reported more frequently by women than mennow that
circumcision is available, condom use is less necessary (7% men,
35% women, OR7.00; 95%CI 2.9316.73); I am less worried about
HIV (16% men, 36% women, OR2.88; 95%CI 1.475.65); I am
more likely to have more than one partner (6% men, 18% women,
OR4.42; 95%CI 1.4213.75); I am more likely to have sex without
a condom (6% men, 18% women, OR 3.33; 95%CI 1.268.78).
Conclusion: Women have favorable attitudes toward male circumcision. While men are counseled about the partial protection of
circumcision against HIV during the procedure, they do not appear to
share this information with their partners. There is need to target
women with education on male circumcision.
TUAC0402
The efficacy of medical male circumcision against HIV
acquisition at 66 months post-procedure in Kisumu, Kenya
S. Mehta1, H. Li1, S. Moses2, K. Agot3, I. Maclean2, D. Hedeker1 and
R. Bailey1
1
University of Illinois at Chicago School of Public Health,
Epidemiology & Biostatistics, Chicago, United States. 2University of
Manitoba, Winnipeg, Canada. 3UNIM Project, Kisumu, Kenya
Presenting author email: rcbailey@uic.edu
Background: In 3 randomized trials, medical male circumcision
(MMC) reduced HIV acquisition in heterosexual men in subSaharan Africa by 60%. At the end of the trials men initially
randomized to control (delayed circumcision) were free to become
circumcised. Men may choose circumcision differentially, which
may confound observed efficacy. We estimated the 66-month
efficacy of MMC against HIV among men retained int he Kisumu
randomiezd trial, accounting for time-varying confounding and loss
to follow-up.
Methods: From 20022005, 2,784 men aged 1824 were enroled
and randomized 1:1 to immediate circumcision or control. At trial
end in December 2006, control men were offered free circumcision.
Follow-up continued through September 2010. HIV status, STIs, and
behavior were assessed at baseline and 6-month intervals thereafter.
Cox proportional hazards regression incorporating time-dependent
inverse probability of treatment weights (IPTW) generated through
marginal structural modeling estimated the efficacy of circumcision
on HIV risk.
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Results: The cumulative 66-month HIV incidence was 7.21% [95% CI
5.908.75%] 4.34% among circumcised men, 10.9% among uncircumcised men. The crude hazard ratio (HR) of HIV seroconversion for
circumcised vs. uncircumcised men was 0.38 [95% CI0.250.55]. In
conventional Cox regression adjusted for variables significant at the
pB0.05 level (age, condom use, incident HSV-2, GUD, penile injuries,
incident gonorrhea or chlamydia), the HR was 0.46 [95% CI0.31
0.69]. In IPTW-adjusted multivariable Cox regression, the HR was
0.43 [95% CI0.260.71].
Conclusion: The efficacy of MMC was sustained at 57% at 66
months, similar to overall findings of the 3 trials under conditions of
randomization (58% at 24 months). The effectiveness of circumcision
against HIV acquisition in program implementation may vary due to
differential selection of circumcision. These findings provide the best
evidence to date of the long-term efficacy of circumcision against HIV
acquisition.
TUAC0403
Decrease of HIV prevalence over time among the male
population of Orange Farm, South Africa, following a
circumcision roll-out (ANRS-12126)
B. Auvert1, D. Taljaard2, R. Sitta3, D. Reach2, P. Lissouba3,
J. Bouscaillou3, B. Singh4, D. Shabangu2, C. Nhlapo5, J. OtchereDarko2, T. Mashigo2, R. Taljaard6, G. Phatedi2, M. Tsepe2, M. Chakela2,
A. Mkhwanazi2, P. Ntshangase2, G. Peytavin7, S. Billy5, A. Puren4 and
D. Lewis4
1
University of Versailles, Versailles, France. 2CHAPS, Johannesburg,
South Africa. 3Inserm U1018-CESP, Villejuif, France. 4NICD-NHLS,
Johannesburg, South Africa. 5SFH, Johannesburg, South Africa.
6
Progressus, Johannesburg, South Africa. 7Hopital Bichat-ClaudeBernard, Paris, France
Presenting author email: bertran.auvert@uvsq.fr
Background: The effect of the roll-out of voluntary medical male
circumcision (VMMC) in Southern and Eastern Africa on HIV
prevalence is unknown. Three years after the beginning of the
Orange Farm (South Africa) VMMC roll-out (ANRS-12126), the
project?s impact on HIV prevalence over time was assessed.
Methods: Two cross-sectional surveys were conducted, one in 2007
2008 (n 1971), before the beginning of the roll-out, and one in
20102011 (n3268). The response rates exceeded 80%. Male
residents aged 15 to 49 were randomly sampled, interviewed,
assessed for circumcision status, counselled and tested for HIV. Blood
samples were tested for HIV and for recent HIV infection using the
BED assay. Prevalence ratios (PR) were calculated using multivariate
(aPR) and propensity score weighted (wPR) Poisson regression
models to assess the association of HIV prevalence and recent HIV
infections with time and circumcision status. Covariates comprised
age group, ethnic group, religion, having children, alcohol consumption, education level, age at first sexual intercourse, marital status
and occupation.
Results: In three years, male circumcision prevalence standardized
on age increased from 17.0% to 53.9%. In the 20072008 and 2010
2011 surveys, the propensity weighted effect of circumcision status
on HIV prevalence was wPR0.37 (95% CI0.190.58) and wPR
0.48 (95%CI0.35-0.65), respectively. HIV prevalence standardized on
age decreased from 12.5% to 9.3%, aPR 0.74 (95% CI0.600.91),
among participants aged 15 to 49, and from 6.2% to 4.2%,
aPR 0.64 (95% CI0.490.85), among participants aged 15 to 29.
Propensity analyses showed that the intervention avoided 536 (95%
CI 1351318) HIV infections in 2011 among the 52,000 adult men
living in Orange Farm.
Track C Epidemiology and Prevention Science
Conclusion: This study shows for the first time that the roll-out of
VMMC in Africa can, if successfully promoted, lead to a decrease of
HIV prevalence over time, detectable three years after its onset.
TUAC0404
Randomized controlled trial of the Shang Ring versus
conventional surgical techniques for adult male
circumcision in Kenya and Zambia
D.C. Sokal1, Q. Awori2, M. Barone3, R. Simba4, K. Bowa5, R. Zulz5,
P. Cherutich6, N. Muraguri6, J.M. Wekesa7, J. Moguche2, P. Kasonde8,
R. Lee9, P. Masson9, P. Perchal3, S. Combes10, C. Hart10, M. Goldstein2
and P. Li2
1
FHI 360, Clinical Sciences, Durham, United States. 2EngenderHealth,
Kisumu, Kenya. 3EngenderHealth, New York, United States. 4Homa
Bay District Hosptial, Homa Bay, Kenya. 5University Teaching Hospital,
Lusaka, Zambia. 6National AIDS and STD Control Program, Nairobi,
Kenya. 7Ministry of Medical Services, Nairobi, Kenya. 8FHI 360,
Lusaka, Zambia. 9Weill Cornell Medical College, New York City, United
States. 10FHI 360, Durham, United States
Presenting author email: qawori@engenderhealth.org
Background: Male circumcision (MC) reduces men’s risk of HIV
infection, but conventional techniques require a high degree of
surgical skill. The Shang Ring provides a minimally-invasive, simpler
and faster approach that requires neither hemostasis nor suturing
and potentially reduces training time. Trial objectives were to
compare pain, acceptability, safety and ease of use of the Shang
Ring versus conventional techniques.
Methods: The Shang Ring consists of inner and outer rings, with
eversion of the foreskin over the inner ring before application of the
outer ring and excision of the foreskin from the underside. Ring
removal is done one week later. We conducted a randomized
controlled trial of the Shang Ring versus conventional MC techniquesforceps guided technique in Homa Bay, Kenya, and dorsal slit
technique in Lusaka, Zambia. We used a visual analog scale to
evaluate pain at five time points in the first 48 hours after surgery.
Clinicians graded adverse events as mild, moderate and severe based
on PSI/WHO criteria, and took photographs to document adverse
events and healing.
Results: We circumcised 200 men at each site. The duration of Shang
Ring procedures was significantly shorter at both sites (p B0.0001),
with medians of 7 versus 20 minutes. At the two-day visit, pain was
similar between groups at both sites. Adverse event rates were 3%
among both study groups. At the 60-day visit, more men in the
Shang Ring group were ‘‘very satisfied’’ with cosmetic appearance,
96% vs 85% (p B0.02) in Kenya, and 97% vs 70% (p B0.01) in
Zambia. Regarding ease-of-use, five of six clinicians had a "strong
preference" for the Shang Ring and considered it "much easier" to
use, and none preferred the conventional technique.
Conclusion: Scale-up of MC in Africa should be easier when providers
begin routine use of devices such as the Shang Ring.
TUAC0405
One arm, open label, prospective, cohort field study to
assess the safety and efficacy of the PrePex device for scaleup of non-surgical circumcision when performed by nurses
in resource-limited settings for HIV prevention
M. Vincent1, S.A. Kaplan2, J.P. Bitega3, M.L. Ngeruka3, C. Karema4 and
A. Binagwaho4
135
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
intervention. The average procedure time in the last 125 subjects
was 2 minutes and 51 seconds (SD 1minute 11 seconds) for
placement and removal time combined.
Conclusion: Our study validated that task shifting MC from
physicians to nurses when using the PrePex device is safe and
effective. The procedure was bloodless, required no injected
anesthesia, no sutures and was performed in a standard consultation
room. The study further validated the effectiveness of our PrePex
training program for nurses. Rwanda intends to implement PrePex
into its national HIV prevention program. PrePex has the potential to
facilitate rapid, safe, non physician MC scale-up programs for HIV
prevention, an imminent need in Sub Saharan Africa where
physicians are a limited resource.
Figure 1.
PrePex MC Method.
MOPDE0104
1
Ministry of Health/TRAC Plus, HIV/AIDS and Sexually transmitted
Infections Department, Kigali, Rwanda. 2Weill Cornell Medical
College, New York, United States. 3Kanombe Military Hospital, Kigali,
Rwanda. 4Ministry of Health, Kigali, Rwanda
Presenting author email: mutabazivincent@yahoo.com
Background: The Rwanda national goal is to offer voluntary male
circumcision (MC) to 2 million men within 2 years to decrease HIV
incidence by 50%, this can only be achieved if nurses can safely and
effectively perform the MC procedure, as there are not enough
physicians in the country. The PrePex non-surgical MC device was
studies for safety and efficacy when MC is performed by nurses.
Safety was defined as under 2% AEs.
Methods: The study was conducted in Kanombe Hospital, Kigali
Rwanda with ethics approval. 10 nurses with no previous knowledge
on the PrePex device were formally trained for 3 days on the PrePex
MC. 575 adult males were enrolled in the study and distributed
between 5 teams of 2 nurses each. Fig1 presents the PrePex MC
method.
Results: All 575 male subjects (100%) achieved the endpoint of
complete circumcision with glans fully exposed. There were 2 device
related moderate AE (rate of 0.35%) and 2 non-related AE (rate of
0.35%), detailed in Table1. All AEs were easily resolved with simple
Service delivery trends in Kenya’s voluntary medical male
circumcision scale-up from 20082011
Z. Mwandi1, A. Ochieng2, J. Grund3, S. Mwalili1, D. Kimanga2,
G. Otieno4, S. Ohaga5, P. Oyaro6, C. Mwangi7, N. Knight1, K. Chesang1
and N. Bock3
1
CDC Kenya, Nairobi, Kenya. 2National AIDS and STD Control
Program, Ministry of Health, Nairobi, Kenya. 3Centers for Disease
Control and Prevention, Atlanta, United States. 4Nyanza
Reproductive Health Society, Kisumu, Kenya. 5Impact Research and
Development Organisation, Kisumu, Kenya. 6Kenya Medical Research
Institute, FACES Program, Nairobi, Kenya. 7Eastern Deanery AIDS
Relief Program, Kisumu, Kenya
Presenting author email: zmwandi@ke.cdc.gov
Background: Three randomized controlled trials demonstrated a 60%
protective effect of voluntary medical male circumcision (VMMC) on
HIV acquisition in men from heterosexual sex. Kenya has adopted a
national strategy to provide VMMC services to 80% of uncircumcised
males aged 1549 years.
Methods: Sites providing VMMC in Kenya as part of the President’s
Emergency Plan for AIDS Relief (PEPFAR) routinely report on program
indicators. We performed a secondary analysis on VMMC data from
20082011 and disaggregated by age, cadre of provider, adverse
Adverse Event
number
#1
Frequency
Adverse Event
Severity
1
VAS Pain of 10, 1 day before
Moderate
Relation
Related to device
removal
Action taken
Outcome
The subject removed the
Resolved
foreskin and device by
himself
#2
1
Mild bleeding - no sutures -
Moderate
due to subjects self-trauma,
cutting his own foreskin
#3
1
Urination stream partially
Moderate
Unrelated to
Pressure applied for
device or
procedure
30 seconds and standard
dressing
Un likely related to
PrePex re-placed 24H
disrupted by the foreskin,
device, Definitely
after first placement
due to erroneous placement
related to
Resolved
Resolved
procedure
#4
1
Elastic ring moved by
Moderate
subjects
#5
1
Bleeding from the frenulum
Moderate
Unrelated to
Re-placement of the
device or
elastic ring
procedure
Possible relation to
One suture
Resolved
Resolved
device
Adverse Events Details.
136
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
events (AEs), service delivery type, and partner acceptance of HIV
testing.
Results: From 2008-2011, 312,789 adolescent and adult males have
been circumcised in 260 CDC-supported sites. The median age was
17 years (range 0-84 years), and 66% were between 15-24 years.
Clinical officers performed 56% of VMMCs, nurses 42%, and medical
officers 2% (p B0.0001). The proportion of VMMCs done by nurses
and clinical officers increased from 69% in 2008 to 99% in 2011 (pB
0.0001). In all, 32.7% of men returned for post-operative review
within seven days. The prevalence of moderate and severe AEs for
the 102,372 clients returning for follow-up was 2.26%. The trend of
AEs among all cadres decreased in 2011with clinical officers and
nurses both registering an AE rate of 1.4%, while medical officers
registered 0%. VMMCs done in mobile settings have increased from
6% in 2009 to 12% in 2011 (pB0.0001). In 2010, HIV testing for
sexual partners of VMMC clients was launched, and 74% of partners
of VMMC clients aged 15 years accepted HIV testing.
Conclusion: Kenya’s shift in cadre of VMMC provider is an effective
and safe strategy to provide large-scale VMMC surgery. A better
understanding of strategies to increase post-operative followup after VMMC surgery is needed. VMMC may be an innovative
approach to provide HIV testing to sexual partners of VMMC clients.
MOPDE0105
Male circumcision in Swaziland: demographics, behaviours
and HIV prevalence
J.B. Reed1, M. Mirira2, J. Grund1, A. Nqeketo3, H. Ginindza3,
D. Donnell4, R. Nkambule3, G. Bicego5, C. Ryan6 and J. Justman7
1
U.S. Centers for Disease Control and Prevention, Center for Global
Health, Division of HIV/AIDS, Atlanta, United States. 2USAID
Swaziland, Mbabane, Swaziland. 3Ministry of Health - Swaziland,
Mbabane, Swaziland. 4Fred Hutchinson Cancer Research Center,
Seattle, United States. 5U.S. Centers for Disease Control and
Prevention Swaziland, Mbabane, Swaziland. 6Office of the Global
AIDS Coordinator, Washington, United States. 7ICAP at the Mailman
School of Public Health at Columbia University, New York
United States
Presenting author email: eso7@cdc.gov
Background: In 2006, the estimated prevalence of circumcised men
in Swaziland was 8%. Between 2007 and 2011, approximately 35,000
men underwent voluntary medical male circumcision, including
11,000 men circumcised in 2011 during a national HIV prevention
campaign, ‘‘Soka Uncobe’’. The Swaziland HIV Incidence Measurement Survey (SHIMS), a nationally representative, household-based
survey of men and women in Swaziland, conducted independently
from the circumcision campaign, assessed health behaviors and HIV
prevalence.
Methods: Between December 2010 and June 2011, SHIMS participants were surveyed about demographic, clinical and behavioral
factors, including self-reported circumcision status by men. All
participants underwent HIV testing.
Results: Of 18, 212 adults surveyed in SHIMS, 7075 (39%) were men
and 16% (1105/7075) were circumcised. Median age at circumcision
was 20 y (interquartile range (IQR) 8, 17), median time since
circumcision was 1.1 y (IQR 0.6-8.0), and 172 men (16%) reported
circumcision in the prior 6 months. Prior HIV testing was more
commonly reported by circumcised compared to uncircumcised men
(77% vs. 49%, pB0.001). Circumcised men were slightly more likely
than uncircumcised men to report always using a condom in the
prior 6 months (39% vs. 33%, p 0.003) and the number of reported
sex partners in the prior 6 months did not differ (1.4 vs. 1.5).
Track C Epidemiology and Prevention Science
Circumcised men had a significantly lower HIV prevalence compared
to uncircumcised men (14% vs. 24%, PR 0.61, 95% CI 0.520.70).
Conclusion: While the prevalence of male circumcision in Swaziland
remains low, it has doubled in the past 5 years from 8% to 16%.
Circumcised men in Swaziland do not report riskier sexual behavior
and are more likely to have been tested for HIV, compared to
uncircumcised men. HIV prevalence was significantly lower in
circumcised men, reinforcing the evidence for a protective effect of
male circumcision provided as a population-level (non-research)
intervention.
C50 - Sexually transmitted infection (STI)
prevention and control
TUAC0203
Increased routine screening for syphilis and falling syphilis
incidence in HIV positive and HIV negative men who have
sex with men: implications for syphilis and HIV prevention
M. Stoové1,2, C. El-Hayek1, C. Fairley3, J. Goller1, D. Leslie4, N. Roth5,
B. Tee6, I. Denham3, M. Chen3 and M. Hellard1,2,7
1
Centre for Population Health, Burnet Institute, Melbourne,
Australia. 2Epidemiology and Preventive Medicine, Monash
University, Melbourne, Australia. 3Melbourne Sexual Health Centre,
Melbourne, Australia. 4Victorian Infectious Diseases Reference
Laboratory, Melbourne, Australia. 5Prahran Market Clinic,
Melbourne, Australia. 6The Centre Clinic, Victorian AIDS Council,
Melbourne, Australia. 7Nossal Institute, University of Melbourne,
Melbourne, Australia
Presenting author email: stoove@burnet.edu.au
Background: Similar to many developed countries, syphilis has reemerged in Australia. Dramatic increases in syphilis have overwhelmingly affected men who have sex with men (MSM) and appear
likely to have contributed to increased HIV transmission. In response,
high MSM caseload clinics in Melbourne, Australia, have maintained
strategies to increase routine syphilis serology for MSM since 2005.
We examined trends in syphilis testing and incidence among MSM
attending high caseload clinics in Melbourne to investigate the effect
of this intervention.
Methods: Syphilis testing data among MSM attending high caseload
clinics in Melbourne (January 2007 to December 2010) were
analysed. Testing rates and infectious syphilis incidence were
determined over time and disaggregated by HIV status and MSM
reporting ‘high risk’ behaviours. Poisson regression was used to test
the significance of trends.
Results: Over four years 16,806 syphilis tests among 6,441 HIV
positive MSM and 24,142 syphilis tests among 17,440 HIV negative
MSM were conducted. Average annual increases in testing among
HIV positive and negative MSM were 7% (95%CI 6%8%) and 12%
(95%CI 11%13%), respectively. Between 2007 and 2010 infectious
syphilis incidence declined from 6.07 to 2.58 per 100PY among HIV
positive MSM (21% average annual decline), and from 3.27 to 0.96
per 100PY among HIV negative MSM (29% average annual decline).
Incidence declined even more substantially in ‘high risk’ HIV negative
MSM 4.10 to 0.76 per 100PY among those reporting 10 partners
in the previous 6 months and 4.29 to 0.82 per 100PY among those
reporting inconsistent condom use. All testing and incidence trends
were statistically significant (p B.01).
Conclusion: Enhanced routine syphilis testing appears to have
contributed to increased syphilis detection and subsequent reduc-
137
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
tions in syphilis incidence among MSM. These findings support
recommendations that syphilis can be controlled among MSM by
sustaining high frequency testing, with important implications for
HIV control among MSM.
TUPDC0102
Partner notification outcomes for MSM and heterosexuals
with STI/HIV: challenges at different stages
F. van Aar1, Y. van Weert1, R. Spijker2, H. Götz3 and E. Op de Coul1
1
National Institute for Public Health and the Environment, Center for
Infectious Diseases Control, Bilthoven, Netherlands. 2STI AIDS
Netherlands, Amsterdam, Netherlands. 3Rotterdam Rijnmond Public
Health Service, Rotterdam, Netherlands
Presenting author email: eline.op.de.coul@rivm.nl
Background: Partner notification (PN) is seen as a vital tool to break
HIV/STI transmission chains. In the Netherlands, studies assessing PN
effectiveness are lacking. Evaluation of current PN practices is
needed to develop new PN interventions.
Methods: PN outcomes were collected through a newly developed
registration form from index patients with HIV, syphilis, and
gonorrhoea visiting five STI centers in 20102011. PN outcomes
(partners being at risk, notifiable, notified, tested, and case-finding
effectiveness (CFEdetected infections/number of partners with a test
result)) were compared between men having sex with men (MSM)
and heterosexuals.
Results: Of all index patients newly diagnosed with HIV/STI (N
282) for whom PN was indicated, 221 MSM and 55 heterosexuals
reported respectively 1,332 and 93 partners at risk. Proportions of
notifiable partners (MSM42%, N555; heterosexuals90%, N84;
pB0.001) and notifiable partners being notified (89%, N494 vs
75%, N63, pB0.001) differed significantly between MSM and
heterosexuals. The overall CFE was 43% for MSM and 33% for
heterosexuals with the largest difference found for HIV (MSM12%,
heterosexuals3%).
Conclusion: The major challenge in PN among MSM remains the
large proportion of unnotifiable (often anonymous) partners. Among
heterosexuals, the actual notification of partners was more difficult.
Anonymous Internet-based PN, could improve both capability
(reachability of unnotifiable partners) and ability (facilitation of the
actual notification process) to notify partners.
TUPDC0106
Sexually transmitted disease diagnoses associated with
exchange sex among Hispanic migrant men who have sex
with men in the United States
E. Valverde1, E. Dinenno1, A. Oster1, P. Chavez1, P. Thomas1,
J. Schulden2 and J. Heffelfinger1
1
Centers for Disease Control and Prevention, Division of HIV/AIDS,
Atlanta, United States. 2National Institute on Drug Abuse (NIDA)
National Institutes of Health (NIH), Bethesda, United States
Presenting author email: eid8@cdc.gov
Background: In 2010, Hispanic migrants accounted for 37% of the
total Hispanic population in the U.S. Relatively little is known about
the high-risk sexual behaviors that may place Hispanic migrant men
who have sex with men (HM-MSM) at risk for infection with sexually
transmitted diseases (STDs).
Track C Epidemiology and Prevention Science
Methods: During 20052007, 2576 Hispanic migrants were surveyed
at three community-based organizations offering services to migrant
communities in five states with small Hispanic populations. Participants reported demographic characteristics, sexual risk behaviors,
migration patterns, and STD diagnoses (syphilis, Chlamydia and
gonorrhea) in the past year. Factors associated pB0.05 with an STD
diagnosis in the past 12 months among HM-MSM in bivariate
analyses were included in a multivariate logistic regression model.
Results: Of 1550 Hispanic migrant men surveyed who reported
having sex in the past 12 months, 353 (23%) reported sex with a
man. Of these 353 men, 26% reported being married, 46% selfidentified as being heterosexual, and 21% as bisexual. In the past
12 months, 58% reported anonymous sex, 57% reported having
sex under the influence of alcohol or drugs, 40% reported
unprotected receptive anal sex, and 8% reported receiving money
or goods for sex. Twenty-nine (8.2%) men received an STD diagnosis.
Only marital status and receiving money or goods for sex were
significantly associated with the outcome variable in bivariate
analyses. In the multivariate logistic regression model, men who
reported receiving money or goods for sex had increased odds of an
STD diagnosis (adjusted odds ratio3.1, 95% confidence interval1.18.7); marital status was not significantly associated with
STD diagnosis.
Conclusion: The prevalence of sexual risk behaviors and STD
diagnoses was high in this population. STD prevention interventions
tailored to non-gay identifying MSM are needed for HM-MSM. Work
is needed to understand factors contributing to participation in
exchange sex among HM-MSM.
C51 - Pre-exposure and post-exposure
prophylaxis
TUAC0102
PrEP has high efficacy for HIV-1 prevention among higherrisk HIV-1 serodiscordant couples: a subgroup analysis from
the Partners PrEP Study
E. Kahle1, D. Donnell2, H. James3, K. Thomas3, G. John-Stewart3,
E. Nakku-Joloba4, E. Bukusi5, J. Lingappa3, C. Celum3, J. Baeten3 and
Partners PrEP Study
1
University of Washington, Epidemiology, Seattle, United States.
2
Fred Hutchinson Cancer Research Center, Seattle, United States.
3
University of Washington, Seattle, United States. 4Makerere
University, Kampala, Uganda. 5Kenya Medical Research Institute,
Nairobi, Kenya
Presenting author email: ekahle@u.washington.edu
Background: Antiretroviral pre-exposure prophylaxis (PrEP) for HIV-1
prevention was highly effective in reducing HIV-1 acquisition by HIV-1
uninfected partners in African heterosexual HIV-1 serodiscordant
couples in the Partners PrEP Study (efficacy67% for oral TDF PrEP and
75% for oral FTC/TDF PrEP). In that study, the placebo arm incidence
was 2%/year. However, PrEP was not effective in two studies among
high-risk African women (incidence 5-6%/year) leading some to
hypothesize that PrEP would not have efficacy in high-incidence
subpopulations.
Methods: The Partners PrEP Study is a randomized, three-arm trial of
daily oral TDF and FTC/TDF PrEP provided to HIV-1 uninfected
members of serodiscordant couples from Kenya and Uganda. At
enrollment, HIV-1 infected partners were not eligible for antiretroviral therapy under national guidelines. We assessed the efficacy of
PrEP among the subset of couples who had higher baseline risk
138
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
characteristics. Higher-risk couples were defined using a previouslyreported risk score composed of baseline factors associated with
HIV-1 transmission (Kahle CROI 2012), including age of the HIV-1
uninfected partner, number of children together, circumcision status
of the male HIV-1 uninfected partner, married and/or cohabiting,
self-reported unprotected sex, and plasma HIV-1 RNA concentrations
in the HIV-1 infected partner.
Results: Among 4747 HIV-1 serodiscordant couples in the Partners
PrEP Study, 1085 (22.9%) were classified as higher-risk. HIV-1
incidence was 5.0/100 person-years (95% CI 3.37.2, 28 transmissions) among those assigned placebo, 1.3/100 person-years (95%CI
0.5-2.8, 7 transmissions) among those assigned TDF PrEP, and 1.1/100
person-years (95%CI 0.42.4, 6 transmissions) among those assigned
FTC/TDF PrEP, resulting in an estimated PrEP HIV-1 protection efficacy
of 72% for TDF PrEP (95%CI 35-88%, p 0.02) and 78% for FTC/TDF
PrEP (95%CI 4691%, p0.006).
Conclusion: PrEP provided substantial protection against HIV-1
acquisition for higher-risk HIV-1 serodiscordant couples. Higher-risk
HIV-1 serodiscordant couples could be a priority population for PrEP
implementation.
TUAC0302
Anticipated risk compensation with pre-exposure
prophylaxis use among North American men who have sex
with men using an internet social network
1
2
3
4
5,6
D. Krakower , M. Mimiaga , J. Rosenberger , D. Novak , J. Mitty ,
J. White6 and K. Mayer5,6
1
Beth Israel Deaconess Medical Center, Division of Infectious
Diseases, Boston, United States. 2Fenway Health/Harvard School of
Public Health/Harvard Medical School, Boston, United States.
3
George Mason University, Fairfax, United States. 4Online Buddies,
Inc., Cambridge, United States. 5Beth Israel Deaconess Medical
Center/ Harvard Medical School, Boston, United States. 6Fenway
Health, Boston, United States
Presenting author email: dkakowe@bidmc.harvard.edu
Background: The iPrEx study demonstrated that pre-exposure
prophylaxis (PrEP) can reduce HIV incidence among at-risk men
who have sex with men (MSM). However, risk compensation (RC)
could negate the benefits of PrEP.
Methods: After the release of iPrEx results, North American
members (n 5035) of an Internet social network for MSM
completed an online survey regarding PrEP. Demographics, sexual
risk behaviors, PrEP interest, and anticipated RC with PrEP use were
assessed through self-report. Multivariable logistic regression procedures adjusted for age, race/ethnicity, and education examined the
association between sociodemographic variables, sexual risk behaviors and anticipated RC.
Results: The mean age was 39 (SD12.8), 90% were from the US,
84% were homosexual/gay and 84% were white. Ninety-three
percent completed some college, 68% earned ]$30,000/year, 25%
had a history of depression, and 5% had received substance abuse
treatment. Sixty-one percent indicated unprotected anal intercourse
with ]1 male partner in the prior 3 months (UAI-3), and 24%
reported UAI after ]5 drinks. On a scale of 1 (no risk) to 10 (high
risk), the average self-perceived risk of HIV acquisition was 3.3
(SD2.3). Seventy-five percent reported interest in using PrEP.
While using PrEP, 20% anticipated they would decrease condom use
for insertive anal sex, whereas 14% indicated they would for
receptive anal sex. Factors associated with increased odds of
anticipated RC for insertive anal sex were UAI-3 (aOR 1.58; 95%
CI1.222.04; p0.0005) and prior substance abuse treatment
(aOR 2.04; 95% CI1.323.16; p0.002). Factors associated with
increased odds of anticipated RC for receptive anal sex were UAI-3
(aOR 1.57; 95% CI1.162.13; p0.004), UAI after ]5 drinks
(aOR 1.43; 95% CI1.09-1.88; p 0.01) and increased self-perceived
risk of HIV acquisition (aOR 1.10; 95% CI1.05-1.17; p0.0003).
Conclusion: A substantial minority of MSM using an Internet social
network anticipate increased unprotected anal sex with PrEP use.
Interventions to minimize risk compensation are warranted.
TUAC0303
Acceptability of HIV pre-exposure prophylaxis (PrEP) with
Truvada among men who have sex with men (MSM) and
male-to-female transgender persons (TG) in northern
Thailand
D. Yang1,2, C. Chariyalertsak3, A. Wongthanee2, S. Kawichai1,2,
K. Yotruean3, T. Guadamuz4,5, V. Suwanvanichkij1, C. Beyrer1 and
S. Chariyalertsak2
1
Johns Hopkins Bloomberg School of Public Health, Baltimore, United
States. 2Research Institute for Health Sciences, Chiang Mai University,
Chiang Mai, Thailand. 3Chiang Mai Provincial Health Office, Thailand
MOPH, Chiang Mai, Thailand. 4Center for Health Policy Studies,
Mahidol University, Bangkok, Thailand. 5University of Pittsburgh
Graduate School of Public Health, Pittsburgh, United States
Presenting author email: dyang20@uic.edu
Background: Northern Thailand has a high burden HIV epidemic
among MSM and TG. Oral PrEP with Truvada has demonstrated
efficacy in preventing HIV among MSM in Chiang Mai, Thailand - an
iPrEX trial site. Determinants of PrEP acceptability are needed to
gauge the potential uptake of this prevention strategy.
Methods: From January to February 2012, 238 MSM and TG
participants, who self-reported as HIV-uninfected or of unknown
status, completed a self-administered survey on hand-held computers. Participants were recruited by venue-day-time sampling and
asked to rate their likelihood of using PrEP at 50% efficacy. PrEP
acceptability was defined as "very likely" to use PrEP. Odds ratios and
95% CIs were calculated to identify determinants of acceptability.
Results: 131 MSM and 107 TG responded, with mean ages of 23.7
and 21.8, respectively. 29% of MSM and 34% of TG had unprotected
anal sex with a male/TG partner in the past 6 months. Prior
awareness of PrEP was high, at 66% among both MSM and TG. 41%
of MSM and 37% of TG were "very likely" to use PrEP; including
respondents who were "somewhat likely" to use PrEP, the rates
increased to 75% and 77% of MSM and TG, respectively. Among
MSM, factors associated with PrEP acceptability included a prior
history of STIs (AOR 3.9; 95%CIs 1.6-9.8) and strong confidence in
taking daily medications for 1 year (AOR 2.7; 95%CIs 1.2-6.2). Among
TG, factors associated with acceptability included prior awareness of
PrEP (AOR 3.3; 95%CIs 1.2-9.0) and having private insurance (AOR
5.0; 95%CIs 1.3-19.0).
Conclusion: PrEP acceptability was higher among MSM and TG who
were aware of their HIV/STI risk and of PrEP, among those who had
strong medication management skills and private insurance. These
findings suggest that knowledge of PrEP and perceived HIV risk, as
well as financial support for PrEP, are important determinants of
uptake.
FRLBC03
Method of hormonal contraception is associated with
lower tenofovir concentration in healthy women
(MTN-001): implications for pre-exposure prophylaxis
139
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
HORMONAL
CONTRACEPTION
NON-HORMONAL
CONTRACEPTION
median (IQR)
median (IQR)
% difference
p-value
321.3 (243.7383.3)
56.1 (.2386.7)
354.9 (283463.6)
88.2 (59.1124.8)
10
57
.20
.001
1587.8 (1276.81903.5)
19
.017
ORAL TFV DOSING
Matrix/Moiety/Parameter
Units
Serum TFV Cmax
Serum TFV Cpre-dose
ng/mL
ng/mL
Serum TFV AUC
ng/mL *hr
Serum TFV Tmax
hours
PBMC TFV-DP Cmax
fmol/10^6 cells
PBMC TFV-DP Cpre-dose
fmol/10^6 cells
PBMC TFV-DP AUC
fmol/10^6 cells*hr
PBMC TFV-DP Tmax
hours
1337 (1051.81602.8)
1 (0.971.1)
46 (20.560.5)
1.02 (0.971.2)
.72
57 (39112.5)
24
.008
10.2 (032.6)
24.6 (10.850.7)
240
.014
272.1 (82.6361.7)
332.5 (186.3474.2)
22
.035
3.9 (1.46.0)
4.1 (2.17.9)
.19
TFV concentrations in peripheral blood.
ORAL TFV DOSING
Matrix/Moiety/Parameter
Units
Tissue TFV
ng/mg
Tissue TFV-DP
fmol/mg
Cervicovaginal lavage
ng/mL
Endocervical Cytobrush
fmol/10^6 cells
HORMONAL CONTRACEPTION
NON-HORMONAL CONTRACEPTION
median (IQR)
median (IQR)
% difference
p-value
.04 (00.24)
0 (00.21)
.6
0 (013.1)
.18
170.5 (010341.9)
58
.57
.95
0 (00)
269.4 (09261.3)
0 (00)
0 (00)
TFV concentrations iat genital tract sites.
J. Coleman1, A. Chaturvedula2, C. Hendrix3 and MTN-001 Protocol
Team
1
Johns Hopkins University School of Medicine, Gynecology &
Obstetrics, Baltimore, United States. 2College of Pharmacy and
Health Sciences at Mercer University, Atlanta, United States. 3Johns
Hopkins University School of Medicine, Medicine, Baltimore, United
States
Presenting author email: jcolem38@jhmi.edu
Background: HIV pre-exposure prophylaxis (PrEP) clinical trials using
oral and vaginal preparations of tenofovir (TFV) in women reported
inconsistent effectiveness. The objective of this study is to determine
if the TFV and TFV diphosphate (TFV-DP) concentrations are
influenced by hormonal contraceptive use.
Methods: This is a secondary data analysis of an open labeled, 3period crossover study of three different daily TFV regimens, each for
6 weeks (oral 300mg TFV disoproxil fumarate [TDF], vaginal 1% TFV
gel [40mg], or both). The study involved 144 healthy, HIV-negative
women, self-reporting use of effective contraception enrolled at 4 US
and 3 African sites. Serum TFV and peripheral blood mononuclear
cell (PBMC) TFV-DP concentrations were determined using validated
LC-MS/MS methods. Noncompartmental methods were used to estimate peak concentration (Cmax), area under the concentration-time
curve (AUC), and pre-dose concentration (Ctau) which were expressed as median and IQR. Wilcoxon rank sum test was utilized to
compare contraceptive groups.
Results: After oral TFV dosing, hormonal contraception use (oral and
injectable) was associated with 240% decreased PBMC TFV-DP Ctau
(p .014), 24% decreased PBMC TFV-DP Cmax (p .008), and 22%
decreased PBMC TFV-DP AUC (p.035) (Table 1). Injectable contraception use was associated with decreased serum TFV Cmax (42%,
p.018), Ctau (210%, p.001), and AUC (54%, p.012) and PBMC
TFV-DP Ctau (350%, p .01). Vaginal TFV dosing was associated with
a significant reduction of serum TFV Ctau in injectable contraceptive
users (1040%, p.000) while the remaining PK parameters were not
statistically different.
Conclusion: Use of hormonal contraception is associated with
decreased serum and intracellular TFV concentrations. Multivariate
population pharmacokinetic analyses are essential to evaluate
potentially confounding covariates, like adherence, which, like
contraceptive use type, are associated with geographic and racial
differences in other analyses. The magnitude of these drug
concentration differences could partially explain PrEP trial outcomes.
FRLBX04
Pre-exposure prophylaxis (PrEP) will have a limited impact
on the prevalence of HIV-1 drug resistance in sub-Saharan
Africa: comparison of mathematical models
D. van de Vijver1, B. Nichols1, U. Abbas2, V. Cambiano3, J. Eaton4,
R. Glaubius5, K. Lythgoe4, J. Mellors6, A. Phillips3, K. Sigaloff7,8 and
T. Hallett4
1
Erasmus Medical Centre, Virology, Rotterdam, Netherlands.
2
Cleveland Clinic Foundation, Infectious Diseases, Cleveland, United
States. 3Infection and Population Health, University College London,
London, United Kingdom. 4Infectious Disease Epidemiology, Imperial
College, London, United Kingdom. 5Cleveland Clinic Foundation,
Infection and Population Health, Cleveland, United States. 6Infectious
Diseases, University of Pittsburgh School of Medicine, Pittsburgh,
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
United States. 7PharmAccess Foundation, Amsterdam, Netherlands.
8
Amsterdam Institute for Global Health and Development (AIGHD),
Amsterdam, Netherlands
Presenting author email: b.nichols@erasmusmc.nl
Background: Pre-Exposure Prophylaxis (PrEP) with tenofovir and
emtricitabine can prevent new HIV-1 infections. There is a concern
that use of PrEP could increase HIV-drug resistance resulting in loss
of future treatment options. Mathematical modelling has been used
to estimate the impact of PrEP on drug resistant HIV-1. We compared
existing mathematical models that studied drug resistance after
implementation of PrEP to determine key areas of consensus and
discrepancy across models.
Methods: We evaluated standardized outcomes from three independent mathematical models that determined the impact of PrEP
on the HIV-(drug resistance) epidemic in heterosexual populations in
sub-Saharan Africa. All models assumed that PrEP was used in areas
where antiretroviral therapy was available. The HIV prevalence
ranged between 8 and 17%. All models assumed that people using
PrEP received a HIV-test every 3-6 months. The models varied in
structure and parameter choices for PrEP coverage (5 to 30% of
the general population), efficacy of PrEP (at different adherence
levels), the rate by which HIV drug resistance emerges and is
transmitted, and the negative impact of PrEP failure on future
treatment.
Results: All models predicted that the prevalence of HIV drug
resistance will increase in the coming 20 years (up to 30% of those
infected), which was mostly explained by expanded access to
antiretroviral therapy (a proportion of people with drug resistance
will have viral suppression as they switched to second line). Of all
infections involving HIV drug resistance after 20 years, 50% to 63%
were ascribed to antiretroviral therapy, 33% to 48% to transmission
of drug resistance andB4% to PrEP.
Conclusion: Mathematical models that varied substantially in
structure and parameter choices predicted that HIV drug resistance
will increase over a period of 20 years. The models predicted that
HIV-1 drug resistance resulting from antiretroviral therapy far
exceeds that from PrEP.
TUPDC0303
Acceptability of oral intermittent pre-exposure prophylaxis
as a biomedical HIV prevention strategyresults from the
South African ADAPT (HPTN 067) Preparatory Study
D. Mark1, K.R. Amico2,3, M. Wallace1, S. Roux1, R. Grant4,5, R. Wood1
and L.-G. Bekker1
1
Desmond Tutu HIV Centre, Institute of Infectious Disease and
Molecular Medicine and Department of Medicine, University of Cape
Town, Cape Town, South Africa. 2Applied Health Research,
Connecticut, United States. 3Center for Health Intervention and
Prevention, University of Connecticut, Connecticut, United States.
4
Gladstone Institute of Virology and Immunology, San Francisco,
United States. 5University of California, San Francisco, United States
Background: Recent trial results confirm potential for antiretrovirals
to prevent HIV-infection. As programme implementers initiate
pre-exposure prophylaxis (PrEP) demonstration projects and consider national plans, research regarding the acceptability of PrEP in
at-risk communities is needed to evaluate its likely uptake and
potential impact in key populations. Intermittent dosing (iPrEP)
deserves particular consideration due to its requirement for sexual
planning.
Methods: Seven focus groups with 6-8 participants per group
(n 46) were conducted. Five were conducted with adults from a
Track C Epidemiology and Prevention Science
high-incidence community and two informant groups with counselors experienced in working with high-risk populations. Attitudes
towards oral PrEP, iPrEP, microbicide gel and sexual planning were
explored. Focus group data were transcribed, coded and analyzed
utilizing framework analysis. Participants self-completed a sexual
planning survey.
Results: 52% were female and 48% male, with a mean age of 28
years. Barriers to PrEP acceptability included perception of antiretrovirals as treatment, side effects, stigma, risk compensation, safety
and efficacy of a new product and dislike of medication. The primary
facilitator of PrEP uptake was its potential for non-consensual use.
iPrEP was favoured over daily PrEP for perceived ease of use with
fewer dosing days. Oral PrEP was largely preferred over microbicide
gel since it was perceived as not requiring disclosure and not coitally
dependent, although others noted microbicides could enhance sex.
On surveys, 64% of days on which sex occurred were reportedly
’planned’. Men were significantly more likely to be able to predict sex
(75% vs. 32% of women). The median number of sex days per week
was two and highest activity days were Friday and Saturday.
Conclusion: PrEP appeared acceptable to target users although
barriers need addressing. Oral iPrEP was preferred over other
regimens. Sexual planning was fair overall, although more than a
third of sex days were unplanned and women fared worse. iPREP
seems feasible in interval-specific form.
TUPDC0305
Experience of a NYC hospital with non-occupational postexposure prophylaxis (nPEP)
A. Urbina1, G. Osorio1, E. Daniel2,3, P. Galatowitsch4, B. Riggan5,
Z. Hennessey5 and V. Sharp1
1
Center for Comprehensive Care, St Luke’s Roosevelt Hospital,
Medicine, New York, United States. 2Center for Comprehensive Care,
St Luke’s Roosevelt Hospital, Emergency Medicine, New York,
United States. 3Emergency Medicine, Columbia University College
of Physicians and Surgeons, New York, United States. 4HealthClear
Strategies, New York, United States. 5Center for Comprehensive Care,
St Luke’s Roosevelt Hospital, New York, United States
Presenting author email: aurbina@chpnet.org
Background: Non-occupational post exposure prophylaxis (nPEP) to
HIV has been available for over a decade. Few institutions have a
coordinated system for providing this service. Since 2009, St. Luke’s
Roosevelt Hospital (SLR) has provided nPEP in its 2 emergency
departments and 3 affiliated outpatient clinics (Centers for Comprehensive Care, CCC). As of 2010, SLR adopted an nPEP protocol
developed by the NYC Department of Health through a funded
grant.
Methods: An extensive, retrospective chart review was conducted to
describe the characteristics of adult patients who received nPEP in
the ED and affiliated outpatient clinics from 12/2009 to 2/2012.
Characteristics of patients who undertook nPEP and completed
follow-up were compared using Fisher Exact and Wilcoxon tests.
Factors associated with completing the nPEP course were analyzed
using multivariate logistic regression.
Results: 216 unique encounters occurred for nPEP (median age29;
range18-62). 34 encounters were from 13 patients with repeat
nPEP visits (mean 2; range 2-3). 138 patients initially presented in
ED (64%). Majority were male (n 180; 83%), white (n 99; 46%),
and insured (n134; 63%).133 of male patients (65%) reported sex
with other men as their HIV risk exposure. Median time from
exposure to presentation was 24 hours (range1-74 hours). 116/138
(84%) patients referred to the CCC completed 4-week follow-up. 109/
116 (94%) patients completed the 28-day nPEP course. For patients
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
who completed nPEP, there were no significant differences seen by
race (p 0.67), age (p 0.85), gender (p0.70), insurance status
(p 0.31), time from exposure to presentation (p0.16), HIV testing
history (p 0.76), and HIV status of partner (p 0.06). There was one
patient that sero-converted after initiating nPEP 32 hours post
exposure.
Conclusion: nPEP is a chemo-prophylaxis intervention that can
prevent HIV acquisition and transmission and provides additional
opportunities for synergistic, behavioral interventions. A multidisciplinary approach is necessary to coordinate care, follow-up,
and supportive counseling.
TUPDC0306
Project PrEP Talkan in-depth qualitative analysis of PrEP
acceptability, expectations and risk compensation beliefs
among United States MSM
K. Underhill1, K. Morrow2, D. Operario3, R. Ducharme4, C. Kuo3 and
K. Mayer5
1
Yale University, New Haven, United States. 2Department of
Psychiatry & Human Behavior, Brown University-The Miriam Hospital,
Providence, United States. 3Department of Community Health,
Brown University, Providence, United States. 4The Miriam Hospital,
Providence, United States. 5The Fenway Institute, Boston,
United States
Presenting author email: kristen.underhill@yale.edu
Background: Recent evidence suggests that oral pre-exposure
prophylaxis may help reduce HIV incidence among men who have
sex with men. Surveys indicate that MSM may be willing to use
PrEP, but our understanding of the expectations and beliefs that drive
these attitudes is incomplete. This formative qualitative study aimed
to identify factors that influence willingness to use PrEP, risk
compensation beliefs, and conceptions of PrEP efficacy among US
MSM.
Methods: This study planned 6-8 semi-structured focus groups, each
including 4-6 men. Participants were recruited from metropolitan
Providence, RI in 201112. Inclusion criteria were the followingbiological male, aged 18, self-reported negative or unknown HIV
status, and self-reported unprotected anal sex with a man of positive
or unknown HIV status in the past 6 months. Discussions were audiorecorded, transcribed, and thematically analyzed to identify factors
influencing PrEP acceptability, risk compensation beliefs, and understandings of efficacy.
Results: Preliminary analyses suggest that willingness to use
PrEP varies and depends on a range of personal and contextual
factors. Participants described how PrEP might benefit segments
of the MSM population at highest risk, including men ‘‘on the
down low,’’ incarcerated men, low-income men, and men with HIVpositive partners. Benefits included increased intimacy with current
partners, risk-reduction for subsequent or concurrent HIV-negative
partners, and reduced worry during sex. But participants voiced
serious concerns about incomplete efficacy, side effects, interaction
with other drugs or alcohol, cost, insurance coverage, FDA
approval, availability, adherence, and potential behavioral impacts.
Many were concerned that PrEP could prompt increased sexual risktaking across the MSM community. Participants also reported
divergent understandings of partial efficacy, emphasizing uncertainty
about how generalized estimates of efficacy would apply to
individuals.
Conclusion: Willingness to use PrEP among MSM is multifaceted, and
in-depth exploration identifies key concerns that affect PrEP acceptability. Results can assist in developing supportive interventions for
men contemplating PrEP use.
Track C Epidemiology and Prevention Science
C52 - Microbicides
WEPDC0101
Sustained release tenofovir and maraviroc from intravaginal
ring in sheep
T.J. Smith
Auritec Pharmaceuticals, Santa Monica, United States
Presenting author email: tsmith@auritec.net
Background: Our goal is to prevent HIV transmission by developing
coitally-independent, woman-controlled methods based on intravaginal rings (IVRs) that deliver antiretroviral (ARV) microbicides. Our
novel pod-IVR technology, which is able to deliver multiple drugs
independently, consists of an unmedicated silicone ring support
holding the drug delivery ‘‘pods’’ in place (Figure 1). Tenofovir and
maraviroc are two of the only antiretrovirals shown to protect against
SHIV transmission in macaques. Here, we describe sheep studies
showing 28-day release of tenofovir and maraviroc from our IVRs.
Methods: IVR blanks containing preformed cavities were fabricated
by injection molding using liquid silicone resin (LSR). Delivery
windows chosen to provide target release rates were fashioned
mechanically in each cavity. The drug pods were placed in the
cavities, back-filled with LSR, allowing controlled, independent
release by diffusion through the delivery windows into vaginal fluid.
Rings were evaluated in 4 sheep for 28 days. Blood and cervicovaginal lavage (CVL) samples were collected throughout the study, and
the tissue samples were collected on day 28. Sample analysis was
performed by LC/MS using methods developed in house.
Figure 1.
Figure 2.
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
Results: CVL levels were constant (14000/9600ng/mL tenofovir,
6300/8600ng/mL maraviroc) for the duration of the study,
indicating that sustained release without initial burst was achieved.
Tissue levels were 1460/ 527ng/g tenofovir, 312/376ng/g
maraviroc. Plasma levels were 9/ 8ng/mL tenofovir, 0.2/
0.2ng/mL maraviroc (Figure 2).
Conclusion: Using our novel IVR platform, we demonstrated the
ability to deliver a combination of tenofovir and maraviroc in a
controlled and sustained method for up to 28 days in sheep.
This opens the door for use of this ARV IVR to protect women from
HIV infection.
WEPDC0102
Sustained-release saquinavir from an intravaginal ring in
sheep
R.A. Willis1, A.M. Malone1, J.A. Moss2, M.M. Baum2, K.L. Vincent3,
M. Motamedi3, S. Kennedy2, J. Gilman1, I. Butkyavichene1,
C. Nguyen1 and T.J. Smith1
1
Auritec Pharmaceuticals, Pasadena, United States. 2Oak Crest
Institute of Science, Pasadena, United States. 3University of Texas
Medical Branch, Galveston, United States
Presenting author email: rwillis@auritecpharma.com
Background: Our goal is to prevent HIV transmission by developing
coitally-independent, woman-controlled methods based on intravaginal rings (IVRs) delivering antiretroviral (ARV) microbicides. Our
novel pod-IVR technology consists of a nonmedicated silicone ring
that holds drug ‘‘pods’’ in place (Figure 1). Saquinavir, the first FDA
approved protease inhibitor, holds significant potential for use as a
microbicide due to its potency and mode of action. Here we describe
a sheep study showing 28 days of saquinavir release from our
pod-IVRs.
Methods: IVR blanks containing preformed cavities were fabricated
by injection molding using liquid silicone resin (LSR). Three delivery
windows per cavity, chosen to provide the target saquinavir release
rate, were fashioned mechanically in each cavity. Saquinavir pods
were placed in the cavities, which were back-filled with LSR, allowing
controlled release of saquinavir by diffusion through the delivery
windows into vaginal fluid. Rings were evaluated for 28 days in 3
sheep. Blood and cervicovaginal lavage (CVL) samples were collected
at predetermined time points throughout the study, and tissue
samples were collected on Days 14 and 28. Sample analysis was
performed by LC/MS using in-house methods.
Results: CVL levels were constant (51/24 ng/mL) throughout
the study, indicating sustained release without initial burst. Tissue
levels averaged 2700/1400 ng/g (Figure 2).
Figure 1. (A) IVR platform showing 4 drug pods. (B) Side view of
pod in ring. (C) Cutway drawing of pod (4) in an IVR (1) with drug
delivery window (3) and backfill of silence (2) to hold pod in place.
Figure 2. Concentrations in 3 sheep.
Conclusion: Using our novel pod-IVR platform, we demonstrated the
ability to deliver saquinavir, a potent protease inhibitor, in a
controlled and sustained manner up to 28 days in sheep. This opens
the door for use of this ARV in future microbicide products to protect
women from HIV infection.
WEPDC0104
Sustained release raltegravir from an intravaginal ring in
sheep
A. Malone1, J. Moss2, R. Willis1, M. Baum2, J. Gilman1,
I. Butkyavichene1, S. Kennedy2, C. Nguyen1 and T. Smith1,2
1
Auritec Pharmaceuticals, Santa Monica, United States. 2Oak Crest
Institute of Science, Pasadena, United States
Presenting author email: amalone@auritecpharma.com
Background: Our goal is to prevent HIV transmission through
development of coitally-independent, woman-controlled methods
based on intravaginal rings (IVRs) delivering antiretroviral (ARV)
microbicides. Our novel pod-IVR technology consists of an unmedicated ring support holding the drug delivery ‘‘pods’’ in place (Figure
1). Raltegravir, the first FDA-approved integrase inhibitor, holds
significant potential for use as a microbicide due to its potency and
mode of action. Here we describe studies showing 28 days of release
of raltegravir from our pod-IVRs in sheep.
Figure 1. (A) IVR platform (B) Side view of ‘‘pod’’ in ring (C)
Cutway drawing of pod (4) in an IVR (1) with drug delivery window
(3) and backfill of silence (2) to hold pod in place.
143
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Figure 2.
Methods: IVR blanks containing preformed cavities were fabricated
by injection molding using liquid silicone resin (LSR). Three delivery
windows per cavity, chosen to provide the target raltegravir release
rate, were fashioned mechanically in each cavity. The raltegravir pods
were placed in the cavities, which were back-filled with LSR, allowing
controlled release of raltegravir by diffusion through the delivery
windows into the vaginal fluid. Rings were evaluated in vivo using 4
sheep for 28 days. Blood and cervicovaginal lavage (CVL) samples
were collected at predetermined timepoints throughout the study
and tissue samples were collected at day 28. Bioanalysis of these
samples was carried out by LC/MS using methods developed in
house.
Results: The CVL levels were constant (257/ 250ng/mL) for the
duration of the study indicating that sustained release without initial
burst was achieved. Tissue levels were 55/83ng/g. Plasma levels
were below 3.5ng/mL for all samples (Figure 2).
Conclusion: Using our novel pod-IVR platform, we demonstrated the
ability to deliver raltegravir, a potent integrase inhibitor, in a
controlled and sustained manner over 28 days in sheep. This opens
the door for use of this ARV in future microbicide products to protect
women from HIV.
WEPDC0105
High maraviroc concentrations in rectal secretions after
oral dosing do not prevent rectal SHIV transmission in
macaques
I. Massud, W. Aung, A. Martin, S. Bachman, J. Mitchell, F. Deyounks,
E. Kersh, C.-P. Pau, W. Heneine and J.G. Garcia-Lerma
Center for Disease Control and Prevention, Atlanta, United States
Presenting author email: jng5@cdc.gov
Background: MVC is a potent CCR5 co-receptor antagonist that is
being considered for pre-exposure prophylaxis for HIV prevention.
We evaluated in macaques the pharmacokinetic (PK) profile of MVC
and assessed efficacy of MVC in preventing rectal SHIV transmission.
Methods: The PK profile of oral MVC (44 mg/kg) was evaluated at
first dose in plasma and rectal secretions in 12 macaques. Half-life of
CCR5-bound MVC was measured using a MIP1-b internalization
assay. Relationship between MVC concentration, CCR5 occupancy,
and protection from infection was evaluated in vitro. Efficacy of
MVC in preventing rectal virus transmission was investigated using a
macaque model consisting of weekly SHIV162p3 exposures. Six
macaques received a dose of MVC 24h before each virus exposure
Track C Epidemiology and Prevention Science
and a second dose 2h thereafter. Four untreated macaques were
controls. Infection was monitored by serology and PCR.
Results: MVC PK profile in macaques was similar to humans. MVC
concentrations peaked at 2h in plasma (median 451 ng/ml) and at
548h in rectal secretions (median 2,329 ng/ml). MVC AUC024h
in rectal secretions was 7.5 times as high as in plasma (median12,720 and 1,685 ngxhr/ml, respectively). At day 4, MVC
concentration in rectal secretions (median 44 ng/ml) was 21.8
times as high as the IC50 value, and was sufficient to fully occupy
CCR5 in PBMCs. The half-life of CCR5-bound MVC in PBMCs was
2.6 days. Despite this favorable PK profile, 5/6 animals receiving MVC
were infected during 5 rectal SHIV exposures as did 3/4 controls.
Conclusion: We identified a dose of MVC that results in local and
systemic drug exposures comparable to humans receiving 300 mg.
Despite high and durable MVC concentrations in rectal secretions,
MVC did not prevent SHIV infection in macaques. This model suggests
that higher MVC concentrations are needed for rectal protection and
highlights the need to better understand the mechanism of low
efficacy and identify protective MVC regimens.
C54 - Antiretroviral treatment of people
living with HIV for prevention
TUAC0103
Lack of effectiveness of antiretroviral therapy (ART) as an
HIV prevention tool for serodiscordant couples in a rural
ART program without viral load monitoring in Uganda
J. Birungi1, H. Wang2, M.H. Ngolobe3, K. Muldoon4, S. Khanakwa3,
R. King5, P. Kaleebu6, K. Shannon4,7, R. Ochai8, J. Montaner4,7,
E. Mills9, L. Laurenco7, N. Abdallar8 and D. Moore4,7
1
The AIDS Support Organisation (TASO), Research and Medical
Capacity Building, Kampala, Uganda. 2University of British Columbia
BC, Vancouver, Canada. 3The AIDS Support Organisation (TASO), Jinja,
Uganda. 4Division of AIDS, University of British Columbia, Vancouver,
Canada. 5University of California at San Francisco, San Francisco,
United States. 6Uganda Virus Research Institute, Entebbe,
Uganda. 7British Columbia Centre for Excellence in HIV/AIDS,
Vancouver, Canada. 8The AIDS Support Organisation (TASO),
Kampala, Uganda. 9University of Ottawa, Ottawa,
Canada
Presenting author email: birungijophine@yahoo.com
Background: Clinical trials have demonstrated antiretroviral therapy
(ART) is highly efficacious in preventing HIV transmission among
sero-discordant couples. We examined the effectiveness of ART as
prevention in a rural program in Uganda where viral load (VL) testing
is not available.
Methods: We conducted a cohort study of HIV sero-discordant
couples aged ]18 years, where the positive partner was a client of
The AIDS Support Organization in Jinja, Uganda. In one group of
couples the positive partner was eligible for ART because of CD4 cell
count 5250 cells/ mL or a WHO Stage III or IV disease. In the second
group, the infected partner was not yet ART-eligible. Both groups
received regular HIV risk-reduction counseling and condoms. The
uninfected partner was HIV tested every three months. We conducted VL testing and genotyping of transmitted viruses.
Results: A total of 586 couples were enrolled, of which 352 (60%) of
the positive participants received ART during the study. The median
duration of ART-use at enrollment was 2.5 years and the median
duration of follow-up was 1.3 years. ART couples were older than
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
non-ART couples (median 42 vs. 40 years for men; 36 vs. 33 years for
women; p B0.001, for both). ART couples were more likely to report
condom-use at last sex (74% vs. 66%; p0.038) and had longer
duration in relationships than non-ART couples (median 12 vs. 9
years; p0.003). There were no differences between the two groups
in terms of male circumcision status, polygymy status, pregnancy
intentions or injectable contraception-use. We found 9 new infections among partners of ART participants and 8 new infections in
partners of non-ART participants, for an incidence rate ratio of 1.16
(p 0.564).
Conclusion: ART-use was not associated with reduced risk of HIV
transmission in sero-discordant couples in a rural program in Uganda
without VL testing.
MOPDC0104
Treatment as prevention in a country with high ART
coveragethe Namibia example
R. Kamwi1, N. Hamunime1, M. Odiit2, J. Gweshe1,
A. Muadinohamba1, E. Shihepo1, H. Van Renterghem2, A. Jonas1,
M. De Klerk1, M. Mahy3, N. Forster1 and K. Kahuure1
1
Ministry of Health and Social Services (MOHSS), Windhoek, Namibia.
2
UNAIDS, Windhoek, Namibia. 3UNAIDS, Geneva, Switzerland
Presenting author email: rkamwi@mhss.gov.na
Background: A recent randomized control trial demonstrated that
antiretroviral therapy (ART) can reduce the sexual transmission of
HIV among sero-discordant couples by over 95%. We assessed the
trends in HIV incidence and ART coverage in Namibia, and project the
coverage of ART through 2015 under WHO-recommended eligibility
criteria and an alternative criterion of a CD4 level below 500 per
mm3.
Methods: ART data was obtained from the electronic Patient
Management System (ePMS) for people receiving HAART, PMTCT
data from the HIS and HIV prevalence among pregnant women f
rom biennial ANC sentinel surveillance. These data were used in
Spectrum software to estimate the number of people newly infected
Figure 2. Trends in number of new infections and people receiving
ART in Namibia, FY 2000/01 to 2012/11.
with HIV and the number of people eligible for ART. ART coverage
was projected per WHO-recommended ART eligibility criteria
(including CD4 B350) and an alternative criterion of CD4 B 500
per mm3.
Results: Namibia has rapidly scaled up ART to 92,134 by March 2011,
corresponding to 84% (76%97%) of those eligible per the 2010
WHO treatment guidelines. If the eligibility threshold is increased to
B 500 CD4 cells per mm3 in 2012, the number of adults eligible for
ART is estimated to increase by 20% (Figure 1). There has been a
rapid decline in new HIV infections from 23000 (1900029000) in
2000/01 to 9000 (600013000) in 2000/11, a 61% reduction. At the
current rate of scale up, Namibia targets 150000 people on ART by
2015/16 which corresponds to 95% of eligible people per WHOrecommended criteria and 80% per an alternative CD4 B 500 ART
criterion.
Conclusion: In Namibia, ART coverage has reached high levels and
incidence is declining rapidly in the past decade. Namibia is ready
to further expand ART to reduce morbidity and mortality and
realize the target of a 50% reduction in sexual transmission by
2015, resulting from the scale-up of prevention and treatment
programmes.
MOPDC0105
Antiretroviral therapy for prevention of HIV transmission in
HIV-discordant couples: a systematic review of the
observational literature
Figure 1. Adults and children receiving ART and estimate numbers
of people eligible per CD4B350 and CD4 B500 criteria, 1990
2016.
A. Anglemyer1, G. Rutherford1, R. Baggaley2, M. Egger3 and
N. Siegfried4
1
University of California San Francisco, Global Health Sciences, San
Francisco, United States. 2HIV/AIDS Department, World Health
Organization, Geneva, Switzerland. 3University of Bern, Institut für
Sozial- und Präventivmedizin, Bern, Switzerland. 4Department of
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Public Health and Primary Care, University of Cape Town, Cape Town,
South Africa
Presenting author email: grutherford@psg.ucsf.edu
Background: HPTN 052 provided clear evidence that early antiretroviral therapy (ART) in HIV-infected partners in serodiscordant
couples decreases the risk of sexual transmission (RR0.04). Before
HPTN 052, ecological studies and models suggested that sexual
transmission was lower in discordant couples in which the infected
partner was on ART. To estimate ART effectiveness from the observational literature, we conducted a systematic review.
Methods: We used standard Cochrane methods to search electronic
databases and conference proceedings without language limits
and identified cohort and case-control studies of ART use in HIVdiscordant couples. Two authors independently examined all identified studies and abstracted data using a standardized form.
Results: We retrieved 1814 references from which 24 were potentially eligible. Seven observational studies met our inclusion criteria.
These studies identified 436 episodes of HIV transmission, 71 among
treated couples and 365 among untreated couples. The summary
rate ratio was 0.34 [95% CI0.13, 0.92], with substantial heterogeneity
(I2 73%). After excluding two studies with inadequate person-time
data, we estimated a summary rate ratio of 0.16 [95% CI 0.07, 0.35]
with no noted heterogeneity (I2 0%). We performed subgroup
analyses to see if the effect of ART on prevention of HIV transmission
differed by the index partner?s CD4 cell count. Among couples in
which the infected partner had ]350 CD4 cells/mL, we estimated
a rate ratio of 0.02 [95% CI 0.00, 2.87]. In this subgroup, all
61 transmissions were in untreated couples. Tests for interaction
between CD4 subgroups and infection risk were not significant.
Conclusion: HPTN 052 has proven that ART is a potent intervention
for prevention of HIV in discordant couples in which the index
partner has between 350 and 550 CD4 cells/mL. The earlier
observational literature is supportive of the findings of HPTN 052,
although the estimated effectiveness is eight-fold less than that found
in the trial.
C57 - Approaches to improving
adherence to prevention interventions
MOPDC0306
Using surveillance data to identify HIV-positive persons outof-care (OOC) in New York City (NYC) and offer linkage to
care and HIV partner services
C.-C. Udeagu, T. Webster-León, A. Bocour, P. Michel and C. Shepard
New York City Department of Health and Mental Hygiene, Bureau of
HIV/AIDS Prevention and Control, Queens, United States
Presenting author email: cudeagu@health.nyc.gov
Background: Persons living with HIV (PLWH) require regular medical
care to achieve a consistently suppressed viral load (VL) and its
associated benefits of reduced morbidity, mortality, and probability of
sexual transmission to HIV-uninfected partners. Only 51% of PLWH
in the US, however, are retained in care. In 2008, the NYC health
department began using its HIV Surveillance Registry (HSR) to identify
OOC PLWH, re-engage them in care, and offer partner services.
Methods: A CD4 or VL report in HSR was considered a proxy for
receipt of care. PLWH were considered OOC and prioritized for
outreach if lacking care during the previous 9 months and had a NYC
residential address at last report in HSR. Located OOC persons were
offered partner and linkage-to-care services. Reasons for OOC were
ascertained, and partners were notified and tested for HIV. Returnto-care was confirmed using HSR.
Track C Epidemiology and Prevention Science
Results: From 7/2008 to 12/2010, 797 PLWH were prioritized for
outreach; 14% were never located. Of 689 who were traced, 229
(33%) were actually current to care in NYC, 30 (5%) had moved or
were incarcerated, 16 (2%) had died, and 414 were verified OOC.
Most verified OOC were black or Hispanic (97%), US-born (73%),
male (55%), or 4049 years old (42%). Once located, 327/414 (79%)
expressed willingness to return to care and received clinic appointments; 237/327 (72%) were confirmed as having returned to care.
Among the 161 who provided reasons for being OOC, the most
commonly reported was ‘‘felt well’’ (41%). Only 52/414 (16%) OOC
PLWH named partners; 40 (62%) of 65 named partners were traced,
and 3 (13%) of 22 partners with unknown or negative HIV serostatus
were newly-diagnosed with HIV.
Conclusion: Health department-based outreach initiatives utilizing
surveillance registries can successfully re-engage OOC PLWH in
medical care, but partner notification among OOC may yield few
new HIV diagnoses.
C58 - Combination of prevention and
treatment of HIV
TUAC0301
HIV-negative and HIV-positive gay men’s attitudes towards
antiretroviral-based preventionsimilar attitudes to
pre-exposure prophylaxis (PrEP) but greater scepticism
among HIV-negative men about ‘treatment as prevention’
M. Holt1, D. Murphy1,2, D. Callander1, J. Ellard1, M. Rosengarten3,
S. Kippax4 and J.B.F. de Wit1,5
1
The University of New South Wales, National Centre in HIV Social
Research, Sydney, Australia. 2Australian Federation of AIDS
Organisations, Sydney, Australia. 3Goldsmiths, Department of
Sociology, London, United Kingdom. 4The University of New South
Wales, Social Policy Research Centre, Sydney, Australia. 5Department
of Social and Organizational Psychology, Utrecht University, Utrecht,
Netherlands
Presenting author email: m.holt@unsw.edu.au
Background: In Australia, debate continues about how to make best
use of antiretroviral-based prevention or ‘treatment as prevention’.
We assessed the attitudes towards antiretroviral-based prevention,
including PrEP, of Australia’s primary affected populationgay men.
We analysed whether HIV-positive and HIV-negative men held
different attitudes to PrEP and HIV treatments.
Methods: A national, online cross-sectional survey was conducted in
AprilMay 2011. The survey included 29 attitudinal items about PrEP,
medicines, condoms and HIV treatments. Differences between the
mean scores for each attitudinal item were assessed with ANOVA.
Multiple linear regression (MLR) was used to identify independent
differences in attitudes between HIV-positive and HIV-negative
men.
Results: 1041 men were included in the analysis (88.3% HIV-negative
and 11.7% HIV-positive). The mean age was 33.3 years (SD 10.8;
range 1869). Most of the sample (94.8%) identified as gay and a
minority (4.3%) as bisexual. HIV-positive and HIV-negative men
agreed on 13 items, such asPrEP is effective in preventing HIV, that
it would make people less responsible, that it should be provided
free of charge and is less effective than condoms. MLR analysis
indicated nine independent differences between the two groups.
HIV-negative men more strongly disagreed that HIV drugs should be
restricted to HIV-positive people or people who have difficulty using
condoms. HIV-positive men agreed and HIV-negative men disagreed
146
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
that taking HIV treatments was straightforward and HIV-negative
men were more sceptical about whether HIV treatment or an
undetectable viral load prevented HIV transmission.
Conclusion: Australian HIV-positive and HIV-negative gay men have
mixed attitudes towards PrEP and HIV treatments. Despite doubts,
HIV-negative men in particular are keen to see PrEP made available.
There are intriguing differences related to ‘treatment as prevention’
while HIV-positive men are enthusiastic about the benefits of HIV
treatment, HIV-negative men remain sceptical about the effectiveness of HIV treatment in preventing transmission.
C59 - HIV counselling, testing and
diagnostic strategies
TUAC0105
The critical role of social cohesion on uptake of HIV testing
and ART in Zambia
S. Gari1, M. Musheke1, H. Ntalasha2, J.R.S. Malungo2 and S. Merten1
1
Department of Epidemiology and Public Health, Swiss Tropical and
Public Health Institute, Basel, Switzerland. 2Department of
Humanities and Social Sciences, University of Zambia, Lusaka, Zambia
Presenting author email: sara.gari@unibas.ch
Background: It has been documented that being HIV positive put
the social safety net under strain preventing people from accessing
HIV care. Yet, to date, the scope of epidemiological research on this
topic remains limited. We tested the hypothesis that family and
community cohesion were associated with uptake of HIV testing and
treatment.
Methods: This research uses data from a randomized crosssectional study of 2443 individuals sampled in communities and
ART clinics in rural and urban Zambia. Associations were examined
using a two step multivariable logistic regression approach. Initially
independent thematic models, adjusted for sociodemographic variables, were created to examine the effect of social support, stigma,
poverty and beliefs. Variables with pB0.2 in the thematic models
were included in a comprehensive multivariable model for each
outcome.
Results: 978 participants (53% women and 44% men) in the
community reported to be tested for HIV. A total of 691, including
those attending the clinics, reported to be on ART (64% women and
36% men). In the final comprehensive models, adjusted for all
covariates, the risk of not being tested was associated with poor
community engagement (OR 1.5 95% CI 1.121.91), low attendance of religious services (OR 1.3 95% CI 1.081.47), problems
with the neighbors (OR 1.2 95% CI 1.061.32) and living in urban
areas (OR 2.8 95% CI 2.063.61). Protective factors were being
women and married. The strongest predictors for non-uptake of
ARVs were domestic violence (OR 1.3 95% CI 1.041.65) and
trust in traditional medicines (OR 1.8 95% CI 1.33.2.47). Being
widowed or divorced showed a statistically significant protective
effect. Anticipated social stigma (OR 1.2 95% CI1.081.36) was
a significant risk factor for testing in the thematic model but the
effect did not hold when adjusted to all covariates. Stigma was not
associated with uptake of ARVs.
Conclusion: Community engagement and community cohesion were
important predictors for uptake of HIV testing while family cohesion
and trust in traditional medicines played a bigger role for treatment
initiation. Targeted community programs to improve social cohesion
on community and family levels can play a critical role in increasing
access to HIV/AIDS services.
Track C Epidemiology and Prevention Science
THAC0405
Peer-delivered HIV testing and counseling among people
who inject drugs in Bangkok, Thailand
L. Ti1, K. Hayashi1,2, K. Kaplan3, P. Suwannawong3, J. Montaner1,4,
E. Wood1,4 and T. Kerr1,4
1
BC Centre for Excellence in HIV/AIDS, Vancouver, Canada.
2
University of British Columbia, Interdisciplinary Studies Graduate
Program, Vancouver, Canada. 3Thai AIDS Treatment Action Group,
Bangkok, Thailand. 4Department of Medicine, University of British
Columbia, Vancouver, Canada
Presenting author email: lianping.ti@gmail.com
Background: HIV testing is a core component of global efforts to
control the HIV epidemic, although in some settings testing rates
remain unacceptably low. In response, several countries have adopted
peer-delivered HIV testing as a means of increasing access to testing.
However, little is known about the acceptability of peer-delivered
testing and counseling among people who inject drugs (IDU).
Methods: Using data derived from the Mitsampan Community
Research Project in Bangkok, Thailand between July and October
2011, three multivariate logistic regression models were constructed
to identify factors associated with willingness to receive peer-delivered
pre-test counseling, rapid HIV testing, and post-test counseling.
Results: Among our sample of 350 IDU, 44%, 38%, and 37% were
willing to receive peer-delivered pre-test counseling, rapid HIV testing,
and post-test counseling, respectively. In multivariate analyses, factors
associated with peer-delivered pre-test counseling includedmale
gender (adjusted odds ratio [AOR] 0.52), binge use (AOR2.39),
and experiencing barriers accessing health services (AOR 4.86)
(all p B 0.05). Factors associated with rapid HIV testing includedbinge
use (AOR 2.23), incarceration (AOR 2.35), avoiding HIV tests
(AOR0.32), experiencing barriers accessing health services (AOR
4.86), and having been to the Mitsampan Harm Reduction
Center (AOR1.76) (all pB0.05). Lastly, binge use (AOR2.49),
incarceration (AOR 1.98), and avoiding HIV tests (AOR 0.26)
(all p B0.05) were significantly associated with peer-delivered posttest counseling.
Conclusion: We found that a substantial proportion of Thai IDU
were willing to receive peer-delivered HIV testing and counseling.
Individuals engaged in high intensity drug use, with a history of
incarceration, and those experiencing barriers to health care were
most willing to access peer-delivered HIV testing services. These
findings highlight the potential of peer-delivered testing to compliment existing HIV testing programs that serve IDU.
C61 - Prevention for the general
population
WEPDC0203
Changes in HIV testing and condom use in Malawi:
longitudinal findings at midterm from the Malawi BRIDGE II
Project
R.N. Rimal1, G. Mkandawire2, W. Dothi2, P. Roberts2, J. Brown3 and
R. Limaye3
1
Johns Hopkins Bloomberg School of Public Health, Health, Behavior
& Society, Baltimore, United States. 2Johns Hopkins Bloomberg
School of Public Health Center for Communication Programs,
Lilongwe, Malawi. 3Johns Hopkins Bloomberg School of Public Health
Center for Communication Programs, Baltimore, United States
147
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Background: With 14.5% HIV prevalence, the southern region of
Malawi is in urgent need of theoretically informed campaigns to
promote behavior change. Since 2010, the BRIDGE II Project has run
a mass media campaign with a potential national listenership of 70%
in conjunction with community-based and interpersonal communication interventions that facilitate behavioral choices around HIV
prevention in over 340 BRIDGE II communities in 11 districts in
southern Malawi. We present midterm evaluation results on two key
outcomes promoted by the campaigncondom use and HIV testing.
Methods: A first-of-its-kind household-based longitudinal study was
conducted in December, 2011 among 685 adults (56% female,
average age 30.2 years, SD10.9), two years after they were first
interviewed before the campaign began. The longitudinal panel was
selected on the basis of a stratified (by intervention or control)
random sample.
Results: Those who remained in the sample were less educated
(p B.01) and poorer (pB.05) than those who dropped out. Compared
to baseline, there was a 25.8% increase in HIV testing (pB.001) and
5.9% increase in condom use (p .054) at midterm. Exposure to a key
program component-the ‘‘Tasankha’’ (‘‘We have decided’’) messagewas associated with testing (r .14, p B.001) and increase in condom use (r.10, p B.05). Exposure to the reality radio program
‘‘Chenicheni Nchiti’’ was associated with condom use (r .10,
p B.05), but not with changes in HIV testing.
Conclusion: HIV testing and condom use significantly improved at
midterm, in comparison to baseline, and exposure to the BRIDGE II
programs was significantly associated with these outcomes. Multiple
sexual partnerships, another intervention-targeted outcome, were
too few to analyze in this sample. Further analyses will explore
the role of interpersonal discussion and community mobilization
activities in propagating intervention messages. Overall, mass
media messages, coupled with community activities, appear to show
promise in the fight against AIDS.
C62 - Prevention for youth and
adolescents
WEAC0102
Transactional sex in South African youth predicted by
primary caregiver HIV/AIDS and extreme socio-economic
vulnerability: multisite studies
L. Cluver1,2,3, M. Orkin4, M. Boyes5, C. Kuo6, F. Gardner5,
M. Kganakga7 and J. Limba8
1
Oxford University and University of Cape Town, Social Policy and
Intervention, Cape Town, South Africa. 2University of KwaZulu-Natal,
HEARD, Durban, South Africa. 3Department of Psychiatry, University
of Cape Town, Cape Town, South Africa. 4University of
WitwatersrandSchool of Public and Development Management,
Johannesburg, South Africa. 5Oxford University, Social Policy and
Intervention, Oxford, United Kingdom. 6Department of Psychiatry
and Human Behavior, Brown University, Providence, United States.
7
Department of Social Development, Government of South Africa,
Pretoria, South Africa. 8Cape Town Child Welfare, Cape Town,
South Africa
Presenting author email: lucie.cluver@spi.ox.ac.uk
Background: Identifying drivers of transactional sex amongst youth
is essential for HIV-prevention. Whilst some suggest this is normative
in Southern Africa, we test a competing hypothesis of familial-level
risk factors.
Track C Epidemiology and Prevention Science
Figure 1.
Predictors of transactional sex: multisite study.
Methods: Two linked South African studies were conducted to
establish and replicate findingsa three-province survey of 1017
year-olds (n6002; 2010) in six urban and rural sites, and an urban
longitudinal survey of 1324 year-olds (n 1025, 73% retention;
20052009). Both focused on high-deprivation sites. Identical
standardized measures were used in multivariate models, controlling
for sociodemographic co-factors.
Results: Transactional sex (primarily amongst ages 15) was
strongly predicted by HIV/AIDS-infection of youth’s primary caregiver
in both studies (multisite surveyp B .001, OR2.85; urban survey pB
.008, OR1.12), but low in youth with healthy or other-sick caregivers.
Most vulnerable were girls ‘dually’ affected by both AIDS-orphanhood and caregiver HIV/AIDSincreasing risk fourfold (multisite survey
312%; x2 10.52, pB.01) and fivefold (urban survey 3%15%; x2
18.8, pB.001) compared to healthy families.
Both studies showed that caregiver HIV/AIDS increased other
potential mechanisms for youth transactional sex, including food
deprivation (e.g. multisite surveyOR3.85, pB.001) and abuse
(e.g. multisite surveyphysical 8%12%, OR1.84; sexual 15%
23%, OR1.73, emotional 4%8%, OR2.01 and domestic violence 5
10%, OR1.96, all p B.001). These three interlinked risk factorsprimary caregiver HIV/AIDS, food deprivation and abuse-had a
strong cumulative impact on youth risk of transactional sex. In
combination, these raised risk from 2%33% amongst boys and 2%
24% amongst girls (multisite survey) and from 412% amongst boys
and 1%57% amongst girls (urban survey). Analyses identified a
‘hyper-vulnerable’ group of dual-affected, abused and food-deprived
youth.
Conclusion: Findings from two large studies demonstrate that
transactional sex is predicted by severe familial risk factors of HIV/
AIDS, poverty and abuse. Prevention efforts must focus on familial
vulnerability if we are to reduce intergenerational transmission of
risk for HIV-infection.
WEAC0105
Education and HIV/AIDS in western Kenya: results
from a randomized trial assessing the long-term
biological and behavioural impact of two school-based
interventions
P. Dupas1, V. Sharma2, G. Makana3, C. Nekesa3 and E. Duflo2
148
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
1
Stanford University, Palo Alto, United States. 2Massachusetts
Institute of Technology, Cambridge, United States. 3Innovations for
Poverty Action, Busia, Kenya
Presenting author email: vsharma@povertyactionlab.org
Background: Between 2003 and 2006, a large randomized trial
was conducted with 328 schools in Western Kenya to compare the
effectiveness of two programs conducted either in isolation or
combined: 1) training three teachers per primary school on the
national HIV/AIDS curriculum; and 2) providing free school uniforms
to students in grades 6 and above to reduce dropout rates. We assess
the long-term impact of these two programs on transmission of
Herpes Simplex Virus type 2 (HSV-2).
Methods: The sample includes 19,310 youths enrolled in grade 6 in
2003 in one of the 328 primary schools. A cross-sectional survey to
measure HIV and HSV-2 prevalence and behavioral outcomes was
administered between February 2009 and March 2011, six to eight
years after the interventions. During a first wave of surveying, 54% of
the youths could be successfully surveyed. Of the remainder, 29%
were randomly selected for ‘‘intensive tracking’’, and 81% of those
were successfully surveyed. We use sampling weights to account for
this sampling strategy.
Results: The HIV prevalence was 0.17% among males (average age:
20.33) and 1.56% among females (average age: 19.93). The HSV-2
prevalence was 7.14% among males and 11.79% among females.
Students in schools where both programs were implemented were
less likely to be infected with HSV-2 than those in control schools
(OR 0.837, p-value: 0.056, 95% CI [0.6971.00]). This effect was
more pronounced for females (OR 0.812, p-value: 0.10, 95% CI
[0.631.04]) than for males (OR 0.888, p-value: 0.37, 95% CI
[0.681.15]). No significant differences in HSV-2 prevalence were
detected between youth in the control group and those in schools
receiving only one of the programs.
Conclusion: The national HIV/AIDS curriculum for primary school
does not seem sufficient, by itself, to reduce risky sexual behaviors
among youths. Ensuring that youths can stay in school appears a
necessary complement.
WEAE0404
Active program participation and HIV risk reduction among
urban youth: findings from the Complementary Strengths
Research Partnership
J. Tiffany1, J. Eckenrode1,2, D. Exner-Cortens2 and S. BirnelHenderson1
1
Cornell University, College of Human Ecology, Bronfenbrenner
Center for Translational Research, Ithaca, United States. 2Department
of Human Development, Cornell University, College of Human
Ecology, Ithaca, United States
Presenting author email: jst5@cornell.edu
Background: The Complementary Strengths Research Partnership
formed in 2005 to explore whether and how active program participation supports and sustains HIV risk reduction practices among
diverse youth in New York City out-of-school-time (OST) programs
within marginalized communities. One further aim of the exploratory
project was to improve and validate measurement tools for assessing
program participation and risk reduction.
Methods: The community-based participatory research project
engaged New York City youth and OST program staff in developing
and piloting study instruments during 2006 and conducted a 3-wave
survey (n 329; 62% female, 37% male, 1% transgender; 74%
heterosexual, 26% LGBTQ; 91% retention at waves 2 and 3) during
20072008. Exploratory and confirmatory factor analyses were used
to develop a new measure of youth program participation. Univariate
and bivariate statistics for individual-level program participation,
social connectedness, HIV risk reduction, and demographics were
explored. Significant (p B.20) bivariate associations were included in
multivariate and multilevel models.
Results: The study produced a new validated measure of active
youth program participation, the Tiffany-Eckenrode Program Participation Scale (TEPPS; Cronbach’s alpha 0.87), and a new composite
measure of HIV risk reduction applicable to urban adolescents with
diverse degrees of sexual experience. Results showed significant
positive associations among program participation, social connectedness, and HIV risk reduction scores (Table 1).
We found that participation interacted with duration of program
involvement, with participation more likely to contribute to sustained
risk reduction among youth involved in programs for longer time
periods (Figure 1).
Also, youth in programs with average or high participation scores
were more likely to sustain risk reduction practices (Figure 2).
Conclusion: These findings support efforts to promote and sustain
HIV risk reduction among young people by increasing meaningful
youth participation in the programs that serve them. Measurement
instruments from this study can aid in program evaluations aimed at
enhancing youth participation opportunities.
Table 1. Correlations among measures at baseline
RISK
REDUCTION
RISK REDUCTION
TEPPS
FAMILY
SCHOOL
CONNECTEDNESS
CONNECTEDNESS
AGE
MEIM
HOUR DURATION
1.00
TEPPS
.257**
FAMILY
.140*
1.00
.294**
.171**
.163**
1.00
CONNECTEDNESS
SCHOOL
CONNECTEDNESS
.335**
1.00
-.172**
.036
AGE
.020
.061
MEIM
.232**
.349**
.231**
HOURS
.020
.198**
.004
.046
DURATION
.104
.047
-.003
.047
.149**
1.00
.044
.089
.127*
1.00
.060
.121*
1.00
.149*
1.00
*p B.05; **p B.01.
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Figure 1.
Track C Epidemiology and Prevention Science
combination of patriarchal norms and individual level financial
constraints, limit VCT for wives of positive men. We explored the
response to conditional cash transfer on disclosure, condom use and
VCT compared to baseline
Methods: Using clinic records we identified sexually active married
men receiving care6 months who had 1) not disclosed their status
to their spouses, 2) their spouses had received no VCT. Baseline
condom use among the presumed serodiscordant couples was
recorded from initial visit/counseling notes. CCT covered travel/
accommodation (US $ 14) to bring the spouse for VCT and encouraged
the men to voluntarily disclose status beforehand. Study participants
completed a questionnaire on demographics, counseling history,
duration of HIV, and reasons for absent disclosure/spouse VCT.
Results: 138 men (60%) had spouses with unknown/never tested
status. In this group baseline disclosure to wife was 29%, condom use
8%, median duration of clinic visits 14.3 months. 38% men reported
travel costs as the main reason for lack of spouse VCT. From the138
men; 94(68%) men received CCT, which was B20% of their monthly
income. 53 (56%) brought their spouses for VCT; 19 (20%) reported
testing elsewhere, and 22 (24%) did not comply. CCT improved
disclosure of HIV status 62% (p B0.05), and condom use 13% (pB
0.08). Factors associated with positive response to CCT were men
B50 years, good ART compliance, and prior self-disclosure of status
to one family member (p B0.05).
Conclusion: A targeted, low cost CCT ($14) can potentially help
avert HIV infections in wives of positive men through promoting VCT
and disclosure. Further studies are needed to review effectiveness,
spillover, ethical aspects, and sustainable means to overcome financial and social constraints among this most vulnerable group of
women.
C64 - Prevention for people who use drugs
THAC0401
The cost-effectiveness of needle-syringe exchange programs
in Eastern Europe and Central Asia: costing, data synthesis,
modeling and economics for eight case study countries
Figure 2.
C63 - Prevention addressing gender
inequalities
WEAD0105
Response to conditional cash transfers: prevention of HIV
infection in wives in Pakistan
A. Khan1, R. Qazi2, N. Nazim3 and A. Khan1
1
Research and Development Solutions, Islamabad, Pakistan.
2
Pakistan Institute of Medical Sciences Hospital, Islamabad,
Pakistan. 3Health Services Academy, Islamabad,
Pakistan
Presenting author email: ayakhan@gmail.com
Background: Timely disclosure of HIV status amongst HIV discordant
couples is important to prevent new infections. In Pakistan, a
D. Wilson1, L. Zhang1, C. Kerr1, A. Kwon1, A. Hoare1, M. WilliamsSherlock2, C. Avila3 and EECA NSEP evaluation working group
1
University of New South Wales, Sydney, Australia. 2UNAIDS,
Moscow, Russian Federation. 3UNAIDS Office, Geneva, Switzerland
Presenting author email: dwilson@kirby.unsw.edu.au
Background: To evaluate the impact and cost-effectiveness of
needle-syringe exchange programs (NSEPs) in Eastern Europe and
Central Asia (EECA) in preventing HIV and hepatitis C virus (HCV)
infections among injecting drug users (IDUs).
Methods: A data triangulation process was conducted across
eight countries in EECA. This informed a health economic analysis
incorporating a mathematical model of HIV and HCV transmission
and disease progression among IDUs. We compared the epidemiological outcomes and costs of NSEP coverage with scenarios of no
NSEPs, with counterfactual receptive sharing determined based on
an empirical relationship of associations with syringe availability in
each country. Outcomes included numbers of HIV and HCV infections
averted, lifetime healthcare costs from a health sector perspective,
and cost per QALY gained. Discounting was applied at 0% and 3%.
Results: There were substantially increased financial investments
in NSEPs over 20052010. The average number of needle-syringes
distributed, and proportion of IDUs reached, across all eight
countries increased by more than 300%. For all eight countries,
150
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
the reported level of receptive sharing decreased with increases
in the per capita distribution of needle-syringes. NSEPs were
estimated to avert 1040% of HIV infections across the eight
countries; a lower percentage of HCV infections were averted
( 525% for six countries and slightly higher in two countries).
NSEPs were found to already be cost-saving or cost-effective, with
respect to HIV alone in the short-term, in four of eight countries,
borderline cost-effective in two countries, but not yet cost-effective
in two countries. When considering the additional health benefits of
averted HCV infections, or the lifetime benefits of HIV infections
averted, NSEPs were very cost-effective to cost-saving in all
countries.
Conclusion: There is strong evidence that NSEPs have been effective
in reducing risk, leading to reduced HIV and HCV infections averted,
and are a very cost-effective public health strategy in EECA.
THAC0402
Switching people who inject drugs from high dead space to
low dead space syringes as a structural intervention to
prevent injection-related HIV epidemics
W. Zule1 and H. Cross2
1
RTI International, Research Triangle Park, United States. 2RTI
International, Global Health Group, Research Triangle Park,
United States
Presenting author email: zule@rti.org
Background: HIV continues to spread among people who inject drugs
(PWID). Previous studies have demonstrated that high dead space
syringes (HDSS) retain over 1000 times more blood after use and
rinsing than low dead space syringes (LDSS) retain. In mathematical
models, this difference was sufficient to prevent or reverse injectionrelated HIV epidemics. The models are supported by an ecological
study that examined syringe type and HIV prevalence in over 50
areas and found that PWID used HDSS in every area where HIV
prevalence among PWID exceeded 6%. Bio-behavioral surveys have
linked sharing HDSS but not LDSS to prevalent HIV infection. An
historical case study demonstrated that PWID will change from HDSS
to LDSS. Taken together these studies suggest that a structural
intervention to switch PWID from HDSS to LDSS could greatly reduce
HIV transmission through syringe sharing and enhance comprehensive HIV prevention efforts for PWID. However, the barriers to such
an intervention and strategies for overcoming them have not been
fully explored.
Methods: We contacted harm reduction organizations, PWID, drug
user groups, researchers and international organizations (e.g. WHO,
UNAIDS, etc.) to identify barriers to changing PWID from HDSS to
LDSS. We also contacted syringe manufacturers to explore the
feasibility of overcoming the barriers that we identified.
Results: Major barriers to switching from HDSS to LDSS wereLDSS are
not available in a variety of sizes; PWID prefer detachable needles;
Table 1.
they may be too expensive; and PWID may be resistant to change.
These are shown in Table 1.
Conclusion: Based on these findings, we developed a series of
steps for implementing a multi-level structural intervention for
transitioning PWID from HDSS to LDSS. The intervention will
require working with policy makers and funders, syringe manufacturers, NSP, PWID service providers, harm reduction organizations
and PWID.
THAC0404
Effects of an HIV/AIDS peer prevention intervention on
sexual and injecting risk behaviours among injecting drug
users (IDU) and their risk partners in Thai Nguyen, Vietnam:
a randomized controlled trial
V. Go1, C. Frangakis2, M. Nguyen Le3, H. Tran Viet4, C. Latkin5, M. Tran
Thi4, T. Sripaipan1, W. Davis1, V. Pham The3 and Q. Vu Minh1
1
Johns Hopkins University, Bloomberg School of Public Health,
Epidemiology, Baltimore, United States. 2Johns Hopkins University,
Bloomberg School of Public Health, Biostatistics, Baltimore,
United States. 3Center for Preventive Medicine, Thai Nguyen, Viet
Nam. 4Johns Hopkins University, Bloomberg School of
Public Health, Epidemiology, Hanoi, Viet Nam. 5Johns Hopkins
University, Bloomberg School of Public Health,
Health Behavior and Society, Baltimore, United States
Presenting author email: vgo@jhsph.edu
Background: Globally, 30% of new global HIV infections involve
injecting drug users (IDUs) and in many countries, including Vietnam,
the HIV epidemic is concentrated among IDUs. We conducted a
randomized controlled trial to evaluate whether a community-based
network-oriented behavioral peer intervention could reduce injection and sexual HIV risk behaviors among IDUs and their network
members.
Methods: 419 HIV-negative index IDU aged 1849 years and 516 of
their injecting and sexual network members were enrolled in this
randomized controlled trial in Thai Nguyen, Vietnam. Each index
participant was randomly assigned to receive a series of six small
group peer educator-training sessions and two 6-month booster
sessions in addition to HIV testing and counseling (HTC) (intervention; n210) or HTC only (control; n 209). Follow-up was
conducted at 3, 6, 9 and 12 months post-intervention.
Results: The proportion of unprotected sex dropped significantly
from 49% to 27% between baseline and 3-month visit among indexnonindex pairs. However, at 12 months, post-intervention, intervention participants had a 14% greater decline in unprotected sex
relative to the control (Wald test10.8, df 4, p .03). This
intervention effect was fully accounted for by trial participants
who had baseline and 12-month visits but missed some in-between
visits, and for whom the control subjects were significantly more
Major barriers to switching PWID from HD
Barrier
Feasible Solution
LDSS are not available in larger sizes (i.e. 1 ml)
Manufacturers are willing and able to produce LDSS in larger sizes
LDSS do not have detachable needles
One manufacturer produces low dead space needles that will fit on standard syringes
LDSS are more expensive than HDSS
This is true in some areas but not others. Major purchasers could negotiate
PWID will be resistant to change
Behavioral change communications to emphasize benefits of LDSS (e.g. do not
waste drugs)
comparable prices
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Track C Epidemiology and Prevention Science
likely to report unprotected sex at 12 months compared to
intervention subjects. The proportion of observed needle-sharing
dropped significantly between baseline and visit 1 (14% vs 3%) and
persisted until 12 months but there was no difference across trial
arms (Wald test 3.74, df 3, p 0.44).
Conclusion: Decreased sexual and injecting risk behaviors noted in all
arms between baseline and visit 1 may be associated with the
HTC received by all participants. Missing some intermittent visits
may account for higher reported unprotected sex among control
participants at 12 months.
FRLBC06
Heroin scarcity in coastal Kenya: consequences for persons
who inject drugs (PWID) and national and provincial
response to the crisis
F. Njenga1, D. Kiima2, M. Siminyu3, E. Munyi4, R. Abdool5,
M. Muthui6, B. Lambdin7, J. Mbwambo8, E. Mwamburi9,
S. McCurdy10, B. Pick11, G. Anderson12, S. Mital13 and R. Needle14
1
National Campaign Against Drug Abuse Authority, Nairobi, Kenya.
Ministry of Medical Services, Division of Mental Health Services,
Nairobi, Kenya. 3Office of the Provincial Director of Medical Services,
Coastal Province, Coastal Province, Kenya. 4Office of the Provincial
Commissioner, Coastal Province, Coastal Province, Kenya. 5UN Office
on Drugs and Crime, Nairobi, Kenya. 6US Centers for Disease Control
and Prevention-Kenya, Nairobi, Kenya. 7Pangaea Global AIDS
Foundation, Oakland, United States. 8Muhimbili University of Health
and Allied Sciences (MUHAS), Dar es Salaam, United Republic of
Tanzania. 9United States Agencey for International DevelopmentKenya, Nairobi, Kenya. 10University of Texas at Austin, School of
Public Health, Austin, United States. 11USAID, Washington, United
States. 12Centers for Disease Control & Prevention (CDC), Division of
Global HIV/AIDS, Atlanta, United States. 13Centers for Disease Control
and Prevention (CDC), Atlanta, United States. 14US Office of Global
AIDS Coordinator, Washington, United States
Presenting author email: fnjenga@africaonline.co.ke
2
Background: In December 2011, major heroin traffickers in Kenya
were publicly named, resulting in a government crackdown pre-
Table 1. Thematic data on drug use
Drugs
Change in type
BEFORE
DURING
heroin
bugizi (rohypnol), valium (diazepam),
of drug
AFTER
heroin
marijuana
How used
Cost
smoke, inject
40200 shillings
smokers shifted to injecting
90600 shillings
once begun injecting, continued
200 shillings
Quality
white crest, brown
adulterated white (pamba), mixed with
back to pre-shortage quality
chalk, cement, aspirin, etc.
Where used
at home, maskanis (drug using
more hidden spots including in fields/bush, Maskanis, new hidden spots, fields/
sites)markets, in the bush, prisons
prison
bush, home, prison
Table 2. Thematic data on drug use consequences
Consequences
Sungu sungu perpetrated
violence(community
BEFORE
community member organized
DURING
Beatings continued
AFTER
Beatings continued, burning of maskanis
violence against PWID
vigilantes)
Withdrawal
Overdose
Happens, constant awareness that if Severe (vomiting, body aches,
Not such a concern, plenty of heroin
they miss a does the feeling of
diarrhea, etc.) Drove people to
‘‘tackiness’’ might descend into
‘‘arosto’’ (withdrawal)
search for heroin day and night
and across the region
occurs
frequently mentioned, tendency
many immediately after heroin back on
to overdose due to prolonged
street and limited use during shortage
withdrawal
Relapse
High
Extreme, nearly entire population of
users
Stigma
Family and neighbors ostracize
Still high, but willingness to
Increased as families and neighbors
them
respond to their needs and
welcome them home when they
disappointed in their relapse. They hid
use for as long as possible, but heroin
are sick
use ‘‘is like a pregnancy, you can only
hide it so long and then everyone knows
and they judge you.’’
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Track C Epidemiology and Prevention Science
Figure 2. Clients Accessing Drug Addiction Services.
cipitating an acute heroin shortage in Kenya’s Coastal region in
December 2010- May 2011. The estimated population of people who
inject drugs (PWID) in Coastal Kenya is 26,667 with 18.3% HIV
prevalence. The purpose of this study was to examine the impact
of the shortage on drug use, HIV risk practices and health of
PWID.
Methods: Cross-sectional rapid assessment methodology was used.
Key informant interviews (N57 male PWID, 23 female PWID) and
focus group discussions (N 41 male PWID, 23 female PWID)
in 12 cities were conducted in March 2012 and analyzed using
ATLAS.ti. Addiction treatment services, detoxification and treatment
administered during and after the period of heroin scarcity were
reviewed.
Results: Consequences of heroin scarcity included withdrawal,
increased heroin prices, decreased purity, shift from smoking
to injecting, increased syringe sharing and violence against PWID
(Table 1 & Table 2). Prices dropped after the crisis with heroin
supply returning. HIV risk behaviors continued and overdose
occurred.
Treatment with methadone was not available during shortage. The
Kenyan government led an emergency response involving other
civil society and emergency organizations. Codeine was procured
and staff trained for the management of acute opioid withdrawal.
Initially, demand soared and new admissions decreased overtime
(Figure 1).
Conclusion: The heroin shortage in Coastal Kenya drove PWID
to increase HIV risk behaviors and many sought treatment.
Codeine is a weak opioid and doses provided were low for heroin
addicts, resulting in many discontinuing detoxification before
treatment was completed. Heroin became increasingly available
and rapid relapse to heroin use occurred. The crisis for PWID
continues in the absence of needle and syringe programs (NSPs)
and medically assisted treatment (MAT). The Kenyan Government
is now making plans for NSP and MAT policy and program
implementation.
C66 - Prevention for men who have sex
with men (MSM)
TUPDC0304
Use of a rapid HIV home test to screen potential sexual
partners prevents HIV exposure in a high-risk sample of
MSM
A. Carballo-Diéguez, I. Balan, T. Frasca, C. Dolezal and J. Valladares
HIV Center for Clinical and Behavioral Studies, NYS Psychiatric
Institute and Columbia University, New York, United States
Presenting author email: ac72@columbia.edu
Background: The FDA is considering licensing OraQuick, a rapid,
oral fluid, HIV antibody test that provides results in 20 minutes, for
over-the-counter sale (‘‘home test’’ or HT). We studied whether
HIV-uninfected, non-monogamous gay and bisexual men living in
New York City who never or rarely use condoms would test their
partners prior to receptive anal intercourse (RAI) as a harm-reduction
approach.
Methods: After baseline assessment and self-testing in our offices,
participants received 16 HT kits to take home as an option to
use with sex partners for three months, after which they were
interviewed.
Results: Of the ethnically diverse 32 men enrolled, 28 completed
all study procedures and 27 used HT kits before intercourse
with approximately 100 partners. Kits were used at participants’
and partners’ homes and occasionally in public places. Nine sexual
partners were found to be infected; five of them were unaware of
their status. Participants showed empathy for partners found to be
infected; no sexual intercourse took place after someone’s infection
was detected. A majority of participants said that having HT kits and
using them shifted their own perceptions of risk and led to changes
in their risk practices. Very few problems occurred related to HT use.
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Most participants expressed a strong desire to continue using the
test and frustration that they could not buy it freely. Testing had high
acceptability among ethnic minority participants and ethnic minority
sex partners.
Conclusion: MSM at high risk can use HT to screen sexual partners,
and many partners will agree to take the test. Use of HT results in
detection of previously unknown infections and avoidance of HIV
exposure. Making HT available within networks where high-risk
sexual practices are common may be a cost-efficient and effective
way to identify previously undetected cases. HT may become an
important harm reduction technology.
THPDC0105
Switzerland has developed a new strategy to break the
chains of new HIV infections among gay men and other
MSM
S. Derendinger and R. Staub
Swiss Federal Office of Public Health, Communicable Diseases, Bern,
Switzerland
Presenting author email: steven.derendinger@bag.admin.ch
Background: Willing to understand what drives the HIV epidemic
among MSM in Switzerland, the Swiss Federal Office of Public Health
(SFOPH) commissioned the development of a mathematical model
(MM). On the basis of its results, the SFOPH developed an Urgent
Action Plan in order to break the chains of new HIV infections among
MSM.
Methods: The MSM epidemic was remodeled from 1980 to 2010 on
the basis of data coming from the Swiss Gay Survey, the Swiss HIV
Cohort and the SFOPH surveillance system. Furthermore, the MM
developed scenarios on how the HIV epidemic could evolve
depending on the changes that were made in the HIV prevention
work among MSM.
Results: According to the MM, in 2010, ‘‘only’’ 13% of the infected
MSM were unaware of their HIV infection yet were the origin of 80%
of the new infections. Moreover, the MM indicates that the average
time to diagnose is only 2.2 years. Finally, if nothing changes, the
number of MSM needing antiretroviral treatment would double in
the following ten years.
Conclusion: The small proportion of MSM that seem to be the
origin of most new transmissions tend to indicate that the spread of
HIV is mainly driven by Primary HIV Infection (PHI) among MSM.
Based on this result, the SFOPH developed an Urgent Action Plan
organised in three action fields. The first action field aims to reduce
the MSM community viral load to the lowest level as possible by
breaking the chains of PHI with a one month campaign, called Break
the Chains, repeated every year. The second action field tends to
reduce the time between infection and diagnosis to 12 months
and encourage non monogamous MSM to seek VCT for HIV, Syphilis,
Gonorrhoea, Chlamydia and Hepatitis. The third action field
concentrates on avoiding HIV and STI transmissions to steady
partners.
C67 - Prevention for transgenders
THPDC0203
HIV testing among transgender persons funded by the
Centers for Disease Control and Prevention in the United
States, Puerto Rico and U.S. Virgin Islands, 20082009
Track C Epidemiology and Prevention Science
N. Habarta, G. Wang and M. Mulatu
Centers for Disease Control and Prevention, Division of HIV/AIDS
Prevention, Atlanta, United States
Presenting author email: nhabarta@cdc.gov
Background: Recent studies indicate high rates of HIV infection
among transgender persons in the United States. However, the
scarce availability of national surveillance data on transgenders limits
our understanding of HIV’s impact on this population. This study
describes the patterns of HIV testing events among transgenders
served in CDC-funded HIV prevention programs nationally.
Methods: In 2008, CDC launched an expanded set of National HIV
Monitoring and Evaluation (NHM&E) testing data requirements
that included a gender variable, with an option for a transgender
category. Using 2008 2009 NHM&E testing data, we conducted
descriptive analyses to examine the number of testing events, newly
identified confirmed HIV positivity, and socio-demographic and risk
characteristics of HIV testing among self-identified transgenders.
Results: Of the 5,522,689 CDC-funded HIV testing events reported
in 2008 2009, 7,620 (0.14%) were conducted among transgenders.
HIV positivity was higher among transgenders (2.6%) than males
(1.0%) or females (0.3%). Blacks (31%) and Hispanics (28%) accounted for larger proportions of transgender testing events than
whites (25%). Similarly, the highest HIV positivity was among blacks
(4.6%) and Hispanics (2.6%) compared to whites (0.6%). While
more testing events were conducted among those 20 29 years
(45.9%), the highest HIV positivity was among those aged 40 49
years (2.9%).
Among transgender testing events that included HIV risk information,
the most frequently reported risk behaviors included sex without
using a condom (56%), sex while intoxicated and/or high on drugs
(22%), and exchange of sex for drug, money, or other materials
(14%).
Conclusion: NHM&E data indicate that transgender testing events
represent a small percentage of the overall testing events but have
higher levels of HIV positivity than male and female testing events. HIV
testing and positivity varied by race, ethnicity, and age. These findings
underscore a great need for expanding targeted HIV prevention
services that are responsive to the needs and socio-demographic
characteristics of transgender persons.
THPDC0204
Transgender in Tamil Nadu are still highly vulnerable to HIV
and STIs: findings from bio-behavioral surveys
L. Ramakrishnan1, P. Goswami1, T. Subramaniam2, S. Mathew1,
S. Ramanathan1, B. George1, R. Adhikary3, M.K. Mainkar4 and
R.S. Paranjape4
1
FHI 360, India, New Delhi, India. 2National Institute of Epidemiology
(NIE), ICMR, Chennai, India. 3FHI 360, Washington, Washington,
United States. 4National AIDS Research Institute-ICMR, Pune, India
Presenting author email: lramakrishnan@fhiindia.org
Background: Transgender persons (TG) face considerable marginalization and are at significant risk of HIV. The Avahan program
included TG as a key focus population for the prevention interventions implemented since 2004 in India. The evaluation of this
intervention included two rounds of bio-behavioral surveys for
tracking outcomes among TG in Tamil Nadu.
Methods: Cross sectional bio-behavioral surveys termed Integrated
Behavioral and Biological Assessments (IBBA) were conducted in
2006 (R1) and 2009 (R2). Those who self-identified as TG, 18 years
and older, were sampled using probability based sampling methods
across five districts in Tamil Nadu. After voluntary consent, face-
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to face interview was used to collect behavioral risk information
and blood and urine samples were collected to test for HIV and
STIs.
Results: 807 Transgender were interviewed during both rounds of
IBBA. The decrease of HIV prevalence among TG between R1 and R2
was not significant12% and 9.8% (p 0.49), respectively. However,
prevalence of lifetime syphilis (any RPR and TPHA positive) decreased
significantly from 16.6% in R1 to 4.2% in R2 (p B 0.001). Proportion
of respondent who reported having been contacted by program peer
educators increased between R1 and R275% and 83% (p 0.02),
respectively, whereas reported visits to program STI clinics decreased
from 75% in R1 to 45% in R2 (p 0.00). No significant change was
observed in reported consistent condom use (CCU) with regular male
partners (34% in R1 and 47% in R2; p 0.06), but the proportion of
TG who reported last time condom use with paying partners
decreased from 93% in R1 to 80% in R2 (p B 0.001). About 61%
of TG reported CCU with paying partners in R2.
Conclusion: Increased peer contacts did not result in improved
condom use. Innovative behavior change communication strategies
and structural interventions are required to increase access to
services among TG for reducing vulnerabilities to HIV and STIs.
C70 - Preventing transmission from
people living with HIV
MOAC0201
Predictors for high vireamia among a treatment-naı̈ve
national HIV cohort in the United Kingdom
A. Brown, A. Aghaizu, G. Murphy and V. Delpech
Heatlh Protection Agency, London, United Kingdom
Presenting author email: alison.brown@hpa.org.uk
Background: Viral load is established as the key predictor for HIV
transmission; patients adherent to treatment have a negligible
transmission risk. In the UK, HIV care is free, and 82% of diagnosed
adults receive treatment. We describe the distribution of viral loads
and determine the predictors for high vireamia among a treatmentnaı̈ve cohort to target groups for prevention.
Methods: Data are taken from HIV positive adults accessing care in
the UK in 2010. Patients diagnosed during 2010 were categorised
as ‘‘recently-infected’’ (through linkage to avidity test results), ‘‘late
diagnosed’’ (CD4 count B350 within three months of diagnosis) and
‘‘other’’. High vireamia was defined as 40,000 copies/mL (in line
with the upper quartile of the treatment-naı̈ve population). Untreated
patients with missing vireamia data (2,343), and those receiving
treatment before 2010 (1,543) were excluded; the demographic
profile of the included and excluded patients didn?t differ. Multivariate
analysis was conducted to identify predictors for high vireamia.
Results: Overall, 8,486 patients were treatment naı̈ve and had a
median viral load of 10,494 copies/mL (inter-quartile range (IQR):
1,60042,223); this compares to 39 (IQR:3949) among the treated
population. The number and proportion of patients with high
vireamia are presented by risk-group in Figure 1.
Predictors for high vireamia includerecent HIV infection (Adjusted
Odds Ratio (AOR) 2.8, 95% CI 2137) and late diagnosis (AOR 2.1,
95% CI 1.72.6) (referencediagnosedB2010); CD4B200 (AOR 3.1
95% CI 2.44.0) (referenceCD4 351500); and sex between men
(AOR 2.8 95% CI 2.13.7) (referenceheterosexual women).
Conclusion: Predictors of high vireamia provide a useful prevention
tool. The near three-fold risk of high vireamia among the recentlyinfected (compared to those diagnosed B2010) highlights the
Track C Epidemiology and Prevention Science
Figure 1.
importance of prompt partner notification. Similarly, elevated vireamia in those diagnosed late-particularly those with CD4 B200demonstrates rapid ARV is critical not only clinically, but also for
prevention.
THAC0201
The threshold for an ART secondary prevention effect on
HIV transmission among men who have sex with men
(MSM) has not been reached in the UK despite high
treatment uptake
A. Brown1, O.N. Gill1, A. Presanis2, V. Delpech1 and G. Murphy1
1
Heatlh Protection Agency, London, United Kingdom. 2Institute of
Public Health, MRC Biostatistics Unit, Cambridge,
United Kingdom
Presenting author email: alison.brown@hpa.org.uk
Background: Studies of HIV-infected people show the great efficacy
of anti-retroviral therapy (ART) at preventing HIV transmission to
uninfected sexual partners. High ART uptake may produce an
additional secondary fall in population transmission through reducing ‘community viral load’. In the UK, HIV care is free and 95% of
the diagnosed HIV-infected are established and retained in care.
Using comprehensive nationwide information, we examined whether
high ART uptake was associated with a fall in HIV transmission among
MSM.
Methods: HIV surveillance data, and sequential Bayesian multiparameter evidence synthesis (s-MPES), which combines direct and
indirect information from multiple sources, was used to measure the
recent trend in the number and proportion of diagnosed HIV-infected
MSM who were infective (viral load 1500 copies/ml) and estimate
the number and proportion of undiagnosed HIV-infected MSM who
were infective. These combined trends were related to indicators of
HIV incidence and the trend in HIV incidence estimated through an
s-MPES extension. Data relate to 2006-10 in the United Kingdom.
Results: In 2010, an estimated 40,100 MSM were HIV-infected; 74%
were diagnosed and in these, ART uptake was 80%. Between 2006
(when ART uptake was 71%) and 2010, the overall proportion of
infective MSM decreased from 47% to 35%, while the number
infective remained around 14,000. Estimated annual MSM HIV
incidence rose from 0.5% in 2002 to 0.9% in 2008. In 2010, 62% of
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Track C Epidemiology and Prevention Science
the estimated infective were undiagnosed, 33% were diagnosed but
untreated, and 5% were on ART.
Conclusion: Optimal ART uptake in recent years, consistent with
clinical guidelines, has led to a fall in the proportion infective
without any apparent effect on numbers infective or on the estimated HIV transmission rate. High ART uptake may moderate but not
control HIV transmission in MSM, and behavioural interventions and
increased testing remain a prevention priority.
TUPDC0203
Four years after the Swiss Statement: transmission risk
decision making in sero-different stable couples
D. Nicca, M. Rasi, S. Stoelzl, P. Schmid, C. Kahlert, P. Vernazza and
Swiss HIV Cohort Study
Cantonal Hospital, St. Gallen, Infectious Diseases and Hospital
Hygiene, St. Gallen, Switzerland
Presenting author email: dunja.nicca@kssg.ch
Background: Stopping transmission of HIV to stable partners is a main
focus of positive prevention initiatives. In January 2008, the Swiss
Commission on AIDS issued a statement indicating that positive
individuals with effective antiretroviral treatment and without STD’s
are not considered sexually infectious. At the same time the
importance of the negative partner’s decision about precautions
such as condom use was emphasized. The aim of this qualitative study
was to explore how negative partners, living in stable sero-different
partnerships, make everyday decisions about dealing with the HIV
transmission risk.
Methods: The Study was conducted at one center of the Swiss HIV
Cohort Study (SHCS). At medical consultations, patients were asked to
provide written study information to their stable partners. Partners
willing to participate were recruited consecutively. Open ended
interviews were conducted with each participant and transcribed
verbatim. Transcripts were analyzed using thematic analysis according
to Brown and Clark (2006).
Results: Ten Caucasian women and seven men, born in different
European countries, gave insight views on how they deal with their
perceived HIV transmission risk. The mean age in this group was 43.3
years (range29-66y). The duration of their relationship ranged from
2-24 years. Lifestyles and sexual preferences were diverse.
Participants experienced significant changes between phases of
relative security and insecurity associated with the possible risk of
HIV transmission. To deal with feelings of insecurity, different types
of decision making were describeda) condom commitment; b) role
governed commitment; c) flexible adaption and d) incongruent
adaption.
Conclusion: To our knowledge this is one of the first studies focusing
perceptions of negative partners in sero-different couples after the
Swiss statement. Participants narratives provided insights into
different decision making strategies, which provide guidance for
individualized counseling and systematic prevention interventions.
WEPDC0205
Effectiveness of behavioral interventions on unprotected
sex among people living with HIV: a system review and
meta-analysis
L. Yin1, N. Wang2, Y. Ruan2, Y. Shao2, S. Vermund1 and H.-Z. Qian1
1
Vanderbilt Institute for Global Health, Nashville, United States.
2
National Center for AIDS/STD Control and Prevention, China CDC,
Division of Virology and Immunology, Beijing, China
Presenting author email: lu.yin@vanderbilt.edu
Figure 1.
Unprotected sex with all sexual partner.
Background: To perform a systematic review and meta-analysis of
the effectiveness of behavioral interventions on unprotected sex
among people living with HIV/AIDS (PLWHA).
Methods: Randomized clinical trials of behavioral interventions
among adult PLWHA published as of November 2011 were identified
by systematically searching nine electronic databases and by crossreferencing. The main study outcomes of interest were unprotected
virginal and/or anal intercourse (UVAI). Summary difference of
standardized mean differences (SMD) between groups, which was
defined as the effect sizes (ES), in both fixed and random effects
models were calculated. Becker’s strategy was used to adjust for any
differences between groups at baseline. When studies reported
dichotomous outcomes, odds ratios were transformed into SMDs
using Cox transformation. Heterogeneity of studies was estimated by
I2 statistic. Begg and Mazumdar rank correlation tests and Egger’s
tests of the intercept were employed to assess indications of
publication bias.
Results: A total of 10,745 PLWHA from 19 studies of behavioral
interventions were included into meta-analyses. Thirteen reported
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Track C Epidemiology and Prevention Science
C72 - Use of the internet and mobile
phones for prevention
WEAC0104
Soap opera video episodes streamed to smartphones in a
randomized controlled trial to reduce HIV sex risk in young
urban African American/black women
R. Jones1, L. Lacroix1 and D. Hoover2
1
Rutgers University, College of Nursing, Newark, United States.
2
Rutgers University, Department of Statistics, Piscataway,
United States
Presenting author email: racjones@rutgers.edu
Background: We tested the efficacy of ‘‘Love, Sex, and Choices’’(LSC),
a 12-week soap opera video series created to reduce HIV risk in the
context of relationship dilemmas, in a randomized controlled trial
among 238 high-risk African American/Black women, aged 1829, in
the urban Northeast.
Methods: 117 were randomized to receive 12-weekly videos of LSC
streamed to smartphones. The other 121 received 12-weekly HIV
prevention messages on smartphones. Baseline and post-intervention interviews at 3 and 6 months were completed by audio
computer assisted self-interview (ACASI). Post-intervention changes
in unprotected vaginal (UVS) or unprotected anal sex (UAS) with high
risk partners (HRP), measured by log transformed vaginal episode
equivalent (VEE) score were compared between intervention arms.
Pooled repeated measures mixed linear models of log (VEE) behavior
at 3 and 6 months with baseline log (VEE) as a predictor were fit.
Results: At baseline, 99% had UVS and 44% had UAS with HRPs. Risk
reduction in VEE from pre to post-baseline was significant (p B0.001)
for both groups. The magnitude of reduction did not statistically
significantly differ by group, p0.23. After adjusting for baseline log
(VEE), women receiving the video intervention had 0.20 units greater
reduction in log (VEE) at 3 and 6 months than equivalent women in
the comparison group; roughly corresponding to a 20% greater
reduction in risk behavior. However 93.1% of participants in the
video group wanted the video series to continue.
Conclusion: ‘‘Love, Sex, and Choices’’ was popular and reduced HIV
risk behavior. The comparison intervention was also a viable HIV
prevention intervention. This is the first study to report on streaming
a soap opera video series to smartphones as a public health
intervention. Increasing smartphone access and video streaming
capability create a paradigm shift, opening new channels to address
health disparities.
Figure 2.
Unprotected sex with HIV-negative sexual partner.
UVAI with any sexual partners, and ten reported UVAI with HIV
negative or unknown status sexual partners (HNUP). Lower likelihood
of UVAI was observed in the intervention groups compared with
control groups either with any sexual partners (mean ES 0.22; 95%
confidence interval [CI] 0.32, 0.11) or with HNUP (mean ES
0.13; 95% CI 0.22, 0.04). Null heterogeneity was observed
across trials. No publication bias was found (Kendall tau0.10;
P 0.63; Egger’s t value 0.15; P0.88). Short-term interventions
with 510 months of follow up were effective in reducing UVAI (15
months 0.27 [ 0.45, 0.10]; 610 months 0.18 [ 0.30,
0.07]), while long-term effectiveness was not statistically significant
(1115 months 0.13 [0.34, 0.08]; 15 months 0.05 [ 0.43,
0.32]).
Conclusion: Our meta-analyses confirmed that short-term behavioral
interventions are effective in reducing UVAI among HIV-positive
individuals irrespective of the type of sexual partners, while the longterm impact is uncertain.
C75 - Integration of HIV prevention and
other health programmes
WEPDC0204
Integration of HIV prevention with health and nutrition
program involving self help group women in Andhra
Pradesh, India
S. Sivalenka1, C. Nitrahally Mallachar2, L.D. Chava3 and S.P. Ravi2
1
Centers for Disease Control and Prevention (CDC), Global AIDS
Program, Hyderabad, India. 2Lepra Society, Secunderabad, India.
3
Society for Elimination of Rural Poverty, Hyderabad, India
Presenting author email: sivalenkas@in.cdc.gov
Background: In India, females constitute 39% of People Living with
HIV/AIDs (PLHAs) (0.9 million). Andhra Pradesh state (AP) with 73%
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Journal of the International AIDS Society 2012, 15 (Suppl 3)
rural population, has the highest number of PLHAs (2007) (0.5
million), and high HIV prevalence among pregnant women (1%)
and female sex workers (9.74%) (HSS 2007).
Methods: The HIV/AIDs prevention component was integrated with
the public sector’s largest community based Health and Nutrition
Program (HNP) involving women Self Help Groups (SHGs), aimed at
empowering rural women on HIV/AIDs prevention and reducing
stigma. Three innovative modules developed in story form with
flipcharts, addressed social norms, gender, personal hygiene, reproductive health, foetal sex determination, fertilization, HIV and stigma
and discrimination. Master trainers trained state and district level
HNP staff, who trained sub district level staff, who in turn trained
SHG women at village level.
Results: 3,244 HNP state and district level staff were trained,
reaching 438,622 (86%) of SHG women in rural areas. More than
40,000 SHG women who perceived themselves at risk for HIV got
tested. HIV/AIDs health resource directories were developed for all
23 districts in AP. Case studies (150) were shared at state/district
advocacy meetings. Indira Kranti Patham-Society for Elimination of
Rural Poverty (IKP-SERP) has planned a phased scale up of this
project across AP in 2012.
Conclusion: With reductions in funding globally for HIV/AIDs
programs, integration of HIV prevention within existing community
based programs will support sustainability, community ownership,
gender issues and in achievement of millennium development goals.
C76 - Structural interventions for HIV
prevention
THAC0301
Structural determinants in MSM HIV
preventionenvironmental and structural factors predict
internalised homonegativity in men who have sex with men
(MSM): findings from the European MSM internet survey
(EMIS) in 38 countries
R.C. Berg1,2, M.W. Ross2,3, A.J. Schmidt4, P. Weatherburn4 and EMIS
Network
1
Norwegian Knowledge Centre for the Health Services, Dept of
Evidence-Based Health Services, Oslo, Norway. 2University of Texas
Health Sciences Center, Houston, School of Public Health, Houston,
United States. 3Malmö University, Faculty of Health and Society,
Malmö, Sweden. 4London School of Hygiene and Tropical Medicine,
London, United Kingdom
Presenting author email: rigmor.berg@nokc.no
Background: Varying patterns of policy and cultural disadvantage
among sexual minorities have recently been pointed to as implicated
in their poorer health outcomes, relative to the heterosexual
majority. We examined the precursors of internalised homonegativity
(IH) within a macro-meso-micro framework, using various data
sources, to help disentangle the complex influences perpetuating
homonegative internalisations among European MSM.
Methods: EMIS is a collaborative study across 38 countries which
during summer 2010 recruited over 180,000 MSM via Internet sites.
The survey included a culturally stable form of the IH scale and
various beliefs and behavioural variables. Additionally, to broaden
the view of macro and meso environment at the level of individual
men with respect to IH, we combined country-level data from
the World Economic Forum, LGB status list, and European Values
Survey.
Track C Epidemiology and Prevention Science
Results: The analyses included 38 countries and 144,177 MSM with a
valid IH score, which varied across Europe, with the highest scores
found in Southeast Europe. In multivariate analyses, at the societal
structure of rule-systems, higher IH was predicted by the absence of
legal rights (b .37 to .42). At the meso-level, IH was predicted by
cultural values regarding homosexuality (b .16). At the individual
level, greater homonegative internalisation was found among
those men who perceived they could not access PEP and HIV
and STI testing in their country (b .21 to .22). Higher IH, in
turn, was associated with not testing for HIV and STIs (b .70
to .57).
Conclusion: As possibly the first multi-level study, EMIS shows that a
homonegative structural and social climate appears to have
pervasive effects on MSM’s evaluation of the self, and greater IH
in turn affected men’s levels of HIV precautionary behaviours. In
addition to the human rights aspect, the EMIS results suggest that
improved affirmative policy environments will have positive health
impacts on MSM populations.
TUPDE0102
Conditional cash transfers improve birth registration and
school attendance amongst orphans and vulnerable
children in Manicaland, Zimbabwe
L. Robertson1, P. Mushati2, J.W. Eaton1, L. Dumba3, G. Mavise3,
J.C. Makoni4, C. Schumacher1, T. Crea5, R. Monasch6, L. Sherr7,
G.P. Garnett1, C. Nyamukapa1 and S. Gregson1
1
Imperial College London, Infectious Disease Epidemiology, London,
United Kingdom. 2Biomedical Research & Training Institute, Harare,
Zimbabwe. 3Catholic Relief Services, Harare, Zimbabwe. 4DOMCCP,
Mutasa, Zimbabwe. 5Boston College, Graduate School of Social Work,
Boston, United States. 6UNICEF, Harare, Zimbabwe. 7University
College London, Infection and Population Health, London
United Kingdom
Presenting author email: l.robertson06@imperial.ac.uk
Background: Cash transfer programmes with (CCT) and without (CT)
conditions may improve the well-being and development of orphans
and other children made vulnerable by HIV (OVC) in sub-Saharan
African populations but evidence of effectiveness in Africa remains
limited.
Methods: Cluster-randomised controlled trial in eastern Zimbabwe,
with 30 clusters divided into ten socio-economically matched triplets.
One cluster from each triplet was randomly assigned to each of three
study arms-CT, CCT or control. Vulnerable households in the CT and
CCT arms received bimonthly payments of $18 plus $4 per child for up
to a maximum of 3 children. In the CCT arm, a 10% penalty was
applied where households failed to comply with conditions regarding
birth registration, immunisation and school attendance. We investigated the health, education and social effects of cash transfers.
Results: 9,811 children aged 017 years living in vulnerable households were recruited. After adjustment for cluster and baseline
covariates, the CT programme reduced the proportion of children
aged 04 years without birth certificates ( 4.8%; 95%CI 13.3% to
3.8%) and with incomplete vaccination records ( 2.1%; 10.7% to
6.5%) and the proportions of children aged 612 years (7.4%,
15.4% to 0.6%) and 1317 years ( 8.5%; 15.0% to 2.0%)
attending school less than 80% of days in the last month. The CCT
programme produced larger, and more frequently statistically
significant, reductions in the primary outcomesit reduced the
proportions of children aged 04 years without a birth certificate
( 16.8%; 24.9% to 8.7%) and with incomplete vaccination
records ( 4.1%; 12.3% to 4.1%), and the proportions of children
aged 612 years (8.1%; 17.0% to 0.7%) and 1317 years
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
( 10.0%; 16.6% to 3.5%) attending school less than 80% of
days in the last month.
Conclusion: Cash transfers, particularly conditional transfers, increased birth registration and school attendance in a low income,
high HIV prevalence setting.
C83 - Reproductive choices and maternal
health
WEAC0103
The next generation: perinatally infected adolescents and
their reproductive health
V. Tepper1, J. Kriebs2, S. Lovelace1 and P. Nair1
1
University of Maryland School of Medicine, Pediatrics, Baltimore,
United States. 2University of Maryland School of Medicine,
Department of Obstetrics, Gynecology and Reproductive Sciences,
Baltimore, United States
Presenting author email: vtepper@peds.umaryland.edu
Background: With advances in the treatment of HIV, vertically
infected young women are surviving into adulthood. Like other
teens, many are sexually active at an early age, have multiple sexual
partners, and use condoms inconsistently or infrequently. These
young women face possible pregnancy and the risk of second
generation mother-to-child transmission.
Methods: This was a retrospective review of the medical records
of perinatally infected young women, followed longitudinally in
a comprehensive university based Pediatric AIDS Program. Data
related to reproductive health decisions, demographic and health
variables were examined.
Results: 89 perinatally infected young women between the ages of
1225 were seen between July 1, 2006 and December 31, 2010.
Among this cohort there were a total of 44 pregnancies resulting in
26 live births, 10 terminations and 9 miscarriages. All exposed infants
were HIV negative. Eight women were in committed relationships at
the time of their pregnancy; three of the pregnancies were planned.
Among the 42 pregnancies, only 6 partners (13.6%) were aware of
the mother’s HIV status at the time of pregnancy. Sixteen percent of
the mothers of girls who became pregnant were alive as compared
with 36% of the mothers of young women who did not become
pregnant during the interval.
Conclusion: In this group of young women with perinatally
transmitted HIV infection none of their infants were infected with
HIV, indicating good adherence with HAART during pregnancy. The
low rate of disclosure to partners is a serious issue with public health
implications. Challenges of negotiating relationships for young
women will be discussed. Demographic variables including as age,
education, mother’s vital status, will be examined as predictors
of pregnancy. Future prospective studies will be discussed
including evaluation of early counseling and support to this group
of women.
THAC0101
Unplanned pregnancy in the 2011 Botswana Antenatal
Clinic Sentinel Surveillance
A.C. Voetsch1, M.G. Anderson2, E. Machakaire1, S. Bodika1, W. Jimbo1,
B.P. Yadav2, M. Schaan3, T. Madidimalo2 and R. Lebelonyane2
1
U.S. Centers for Disease Control and Prevention, Division of Global
HIV/AIDS, Gaborone, Botswana. 2Ministry of Health, Department of
Track C Epidemiology and Prevention Science
HIV/AIDS Prevention and Care, Gaborone, Botswana. 3BotswanaHarvard Partnership for HIV Research and Education, Gaborone,
Botswana
Presenting author email: voetschd@bw.cdc.gov
Background: In Botswana, over 30% of pregnant women are HIVpositive. The 2007 Botswana Family Health Survey showed that
51% of women used some form of contraception, predominantly
condoms. Preventing unintended pregnancies is the second prong of
the WHO four-prong approach to a comprehensive prevention of
mother-to-child transmission (PMTCT) program. We used data from
the 2011 Botswana Antenatal Clinic Sentinel Surveillance to determine
the number of, and factors associated with unplanned pregnancies.
Methods: Pregnant women aged 1549 years presenting for the first
time to one of 262 selected antenatal clinics in all 24 health districts
from August 1 through October 28, 2011 were included. Blood
routinely drawn for routine antenatal care was tested for HIV using a
two-test algorithm. A one-page form was completed for all participants that included demographic information, gravidity, HIV testing
history, and planned pregnancy (‘‘Was this pregnancy planned?’’).
Logistic regression analysis was used to determine factors associated
with unplanned pregnancy, adjusted for linear and quadratic effects
of age and for health district.
Results: Of the 6745 participating women, 6667 (98.8%) responded
to the planned pregnancy question. Of these, 3383 (51%) reported
that the current pregnancy was unplanned. Women aged 1519
years and 4049 years reported the highest rates of unplanned
pregnancy (68% and 67%, respectively). Unplanned pregnancies
were higher among HIV-positive (56%) than HIV-negative women
(49%). In a multivariable model, unplanned pregnancy was associated with unemployment (odds ratio (OR 1.29, 95% confidence
interval (CI) 1.151.44), being unmarried (OR2.17, 95% CI
1.812.60), having two or more previous pregnancies (OR 1.83,
95% CI 1.602.10), and having a previous positive test for HIV
(OR 1.73, 95%CI 1.511.99).
Conclusion: The higher proportion of unplanned pregnancies among
those who knew they were HIV-positive prior to the survey and among
multigravid women suggest that current family planning services need
to be strengthened as part of the Botswana PMTCT program.
THAC0106
Where do women who deliver at home fall through cracks
in the PMTCT continuum of care services? A retrospective
study of service uptake among mothers who delivered at
home in Zimbabwe
K.A. Webb, D. Patel, G. Mujaranji and B. Engelsmann
Organisation for Public Health Interventions and Development
(OPHID) Trust, Harare, Zimbabwe
Presenting author email: karen.myllynen.webb@gmail.com
Background: Uptake and retention of mothers and babies along the
PMTCT continuum of care services (Figure 1) is vital for preventing
HIV transmission. Home delivery limits PMTCT programme coverage.
Over one third of women in Zimbabwe deliver at home. Mothers
who delivered at home were interviewed retrospectively regarding
health service uptake to identify potential gaps for intervention in
the PMTCT service continuum.
Methods: In June 2011, mothers in Mashonaland Central province
who delivered at home in the previous 12 months were enrolled in
this descriptive retrospective study. A minimum sample of 351
women was interviewed using a structured questionnaire following
written consent. Sample size was determined using EPI Info Stat-Cal
software and data entered and analysed using EPI Info and SPSS.
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Figure 1.
Track C Epidemiology and Prevention Science
PMTCT Continuum of Care Services.
Results: Of 355 women interviewed, 80.2% booked for antenatal
care (ANC), though 163 (57.2%) made their first ANC booking
after 20 weeks. 277 tested for HIV (78%) while pregnant and 15 of
the 20 who reported testing positive were enrolled in a PMTCT
programme. The vast majority (89%) of women said their home
birth was unplanned and 74.6% reported booking for delivery at a
health facility, though 47 women (13.2%) reported zero uptake
for any antenatal or intrapartum services. 313 (88.2%) attended
post-natal check-ups for their baby, but only 36.1% did not
for themselves. 70.4% of women (250) received no post-natal
counselling.
Conclusion: The majority of mothers who delivered at home
demonstrated high levels of service uptake during antenatal and
postpartum parts of the PMTCT continuum. Strategic efforts
required to correct gaps and missed opportunities to provide PMTCT
services through routine maternity care include support for early
ANC booking, overcoming barriers to facility birth at time of delivery,
and ensuring post-natal care and counselling for all mothers. Further
study and outreach is required to access and mobilise the ‘zero
uptake’ mothers for health service uptake.
TUPDC0202
Safer conception options for HIV serodiscordant couples in
the United States: experience of the National Perinatal HIV
Hotline and Clinicians’ Network
S. Weber1, J. Waldura1 and D. Cohan2
1
UCSF, Family & Community Medicine, San Francisco
United States. 2UCSF, Obstetrics & Gynecology, San Francisco,
United States
Presenting author email: sweber@nccc.ucsf.edu
Background: Approximately 50% of the estimated 140,000 heterosexual HIV serodiscordant couples in the United States desire
Direction of discordance
Number of calls
Percentage
Male HIV/ Female HIV 127
83.6%
Female HIV/ Male HIV Male HIV/ Surrogate
14
11
9.2%
7.2%
Total
152
100%
children. Serodiscordant couples and their providers may not know
the range of options to help reduce the risk of HIV transmission to
the uninfected partner during conception attempts. Moreover, many
couples lack access to assisted reproduction technologies, such as
sperm washing and in vitro fertilization. To help address these gaps
in knowledge and access, the National Perinatal HIV Hotline and
Clinicians’ Network provide consultation and referral to clinicians and
serodiscordant couples in the United States seeking safer conception
options.
Methods: Calls to the National Perinatal HIV Hotline and Clinicians’
Network from clinicians and patients seeking information and
referral for safer conception options were analyzed to determine
the number of calls, the direction of serodiscordance in the couple,
and the types of question asked.
Results: From 2006 to 2011, there were 152 calls regarding conception for serodiscordant couples, 68 from patients and 84 from
clinicians. Call volume increased significantly over time (p value for
trendB0.001, Figure 1). 63% requested referrals for assisted
reproduction. 34% sought risk reduction options when assisted
reproductive technologies were unavailable or unaffordable, including pre-exposure prophylaxis (PrEP) and timed intercourse (Figure 2).
A majority of the calls (83.6%) related to HIV male/HIV- female
couples (Table 1).
Conclusion: The Perinatal HIV Hotline and Clinicians’ Network is
increasingly utilized by clinicians as a resource for expert advice on
periconception HIV risk reduction options and by HIV-affected
couples seeking access to providers supportive of their reproductive
health decisions. Providing safer conception options to serodiscordant couples is a critical component of promoting the reproductive
rights of HIV-affected couples in the United States.
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track C Epidemiology and Prevention Science
Abstract Coding Guide
Example: MOAA01(Weekday) MO (Session type) AA (Session order) 01
Weekdays: SU (Sunday), MO (Monday), TU (Tuesday), WE (Wednesday), TH (Thursday), FR (Friday)
Session types: oral abstract sessions AA (Track A), AB (Track B), AC (Track C), AD (Track D), AE (Track E), AX (Cross-Track), LBA (Late
Breaker Track A), LBB (Late Breaker Track B), LBC (Late Breaker Track C), LBD (Late Breaker Track D), LBE (Late Breaker Track E), LBX (Late
Breaker Cross-Track); oral poster discussions sessions PDA (Track A), PDB (Track B), PDC (Track C), PDD (Track D), PDE (Track E) PDX
(Cross-Track)
Session order: 01, 02, 03, 04, etc.
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
http://www.jiasociety.org/index.php/jias/article/view/18442 | http://dx.doi.org/10.7448/IAS.15.5.18442
Track D Social Science, Human Rights and Political Science
D1 - Combination prevention programmes
Table 2. Intervention effects on HIV/STI incidence after 12
months, excluding women who were HIV-positive or had active
STIs at enrollment, Ciudad Juarez
MOAD0405
Efficacy of combined sexual and injection risk reduction
interventions for female sex workers on the Mexico-US
border: differential effects in the presence of a
community-wide structural intervention
1
2
3
4
5
S. Strathdee , R. Lozada , G. Martinez , G. Rangel , H. Staines ,
D. Abramovitz6, A. Vera7, C. Magis-Rodriguez8, T. Patterson9 and
Proyecto Mujer Mas Segura
1
University of California San Diego School of Medicine, Medicine, La
Jolla, United States. 2ISESALUD, Tijuana, Mexico. 3SADEC-FEMAP,
Ciudad Juarez, Mexico. 4COLEF, Tijuana, Mexico. 5Universidad
Autonoma de Ciudad Juarez, Ciudad Juarez, Mexico. 6University of
California, San Diego, Medicine, La Jolla, United States. 7Universidad
Autonoma de Baja California, Tijuana, Mexico. 8CISIDAT, Mexico City,
Mexico. 9University of California, San Diego, Psychiatry, La Jolla,
United States
Presenting author email: sstrathdee@ucsd.edu
Background: We evaluated brief combination interventions to
simultaneously reduce sexual and injection risks among female sex
workers who inject drugs (FSW-IDUs) in Tijuana (TJ) and Ciudad
Juarez (CJ) Mexico during 2008-2010, when harm reduction was
expanding in TJ, but not CJ.
Methods: FSW-IDUs ]18 years reporting recently sharing injection
equipment and unprotected sex with clients participated in a
randomized factorial trial comparing four brief, single-session
combinations of active motivational-interviewing and didactic interventions focused on negotiating safer-sex in the context of drug
use and safer-injection skills. The injection intervention included
Adjusted
Predictor
Relative Risk
95% CI
0.44
0.19, 0.99
Active Injection Risk and Didactic Sex
1.15
0.58, 2.28
Risk Inetevention
Active Sex Risk InterventionActive
1.12
0.56, 2.25
1.02
1.00, 1.05
1.66
0.98, 2.80
Intervention Group (ref-Didactic Sex
Rick interventionDiadactic injection
Risk)
Active Sex Risk Intervention and Didactic
Injection Risk Intervention
Injection Risk Intervention
Amount earned per unprotected sex act
(USD)
Used cocaine the months poor to
enrollment
Table 1. Intervention effects on HIV/STI incidence after 12
months, excluding women who were HIV-positive or had active
STIs at enrollment, Tiujana
Adjusted
Predictor
Relative Risk
95% CI
0.41
0.18, 0.91
0.84
0.38, 1.84
Active Sex Risk InterventionActive
0.36
0.15, 0.85
Injection Risk Intervention
of unprotected sex acts with
1.01
1.01, 1.02
2.61
1.38, 4.91
Intervention Group (ref-Didactic Sex
Rick intervention-Diadactic injection
Risk intervention)
Active Sex Risk Intervention and Didactic
Injection Risk Intervention
Active Injection Risk and Didactic Sex
Risk Inetevention
non-regular clients for month poor
to enrollment
Anested during the six months poor to
enrollment
Figure 1. Plot of proportional odds of higher receptive needle
sharing for intervention group by visit.
a video made by FSW-IDUs. Women underwent quarterly interviews and testing for HIV, syphilis, gonorrhea, Chlamydia and
Trichomonas. Poisson regression with robust variance estimation
and repeated measures ordinal logistic regression via GEE examined
effects on HIV/STI incidence and receptive needle sharing frequency,
respectively.
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Results: Of 599 initially HIV-negative FSW-IDUs (TJ: N 296; CJ:
N303), quarterly retention was]90%. After 12 months, HIV/STI
incidence decreased 50% in the active vs. didactic sex intervention
(TJ: AdjRR:0.41, 95%CI: 0.180.91, p0.03; CJ: AdjRR: 0.44, 95%CI:
0.190.99, p0.05)-see tables.
In CJ, women receiving active vs. didactic injection risk interventions decreased receptive needle-sharing by 84% vs. 71%, respectively (p 0.05); in TJ, receptive needle-sharing declined by 95%,
but was similar in active vs. didactic groups (p 0.54). TJ women
reported significant increases in access to syringes and condoms, but
CJ women did not-see figure.
Conclusion: In both cities, a 30-minute intervention promoting safersex in the context of drug use significantly reduced HIV/STI incidence
with sustained effects at 12 months. Expanding free access to sterile
syringes coupled with brief, didactic education on safer injection
was both necessary and sufficient in achieving dramatic, sustained
injection risk reductions in TJ. In the absence of expanding syringe
access in CJ, the injection risk intervention still achieved significant,
albeit more modest reductions, suggesting that community-level
interventions incorporating harm reduction are more powerful than
individual-level interventions for reducing injection risks.
MOAE0202
Is treatment as prevention the new game-changer? Costs
and effectiveness
T. Bärnighausen1,2, D. Bloom1 and S. Humair1,3
1
Harvard School of Public Health, Boston, United States. 2Africa
Centre for Health and Population Studies, University of
KwaZulu-Natal, Mtubetuba, South Africa. 3School of Science and
Engineering, Lahore University of Management Sciences, Lahore,
Pakistan
Presenting author email: tbaernig@hsph.harvard.edu
Background: The results of the HPTN 052 study, which showed
antiretroviral treatment (ART) is highly effective in reducing HIV
transmission, have been hailed as a ‘‘game-changer’’ in the fight
against HIV, leading to calls for significant scaling up of treatmentas-prevention (TasP). But it is unclear how TasP could be financed,
given flat-lining support for global HIV programs. We assess if TasP is
indeed a game-changer against HIV, or if comparable benefits can be
obtained at a lower cost by scaling up existing interventions such
medical male circumcision (MMC). We also assess the impact of
TasP in combination with MMC. Since MMC is currently being scaled
up in many countries in sub-Saharan Africa, the effectiveness of
TasP in conjunction with MMC is a highly policy-relevant question.
Methods: We formulate a new mathematical model to overcome
challenges in predicting the effectiveness of untried mass interventions (lack of a historical epidemic trajectory) and in predicting the
combined effectiveness of different prevention interventions. Our
model uses simple behavioral assumptions to estimate new HIV
infections instead of estimating parameters by fitting a curve to a
disease history.
Results: For South Africa, a combination of high ART coverage at
CD4B 350/ml and circumcision coverage provides approximately
the same HIV incidence reduction as TasP (defined as universal ART
for all HIV-infected persons) at a cost $5 billion less over 2009
2020. Circumcision outperforms high ART coverage at CD4 B350/ml
(and TasP) significantly in cost per infection averted*$1096 compared to $6790 per infection averted. Further, circumcision increases
in cost-effectiveness over time and becomes cost saving after 2040.
Conclusion: The preventive benefits of ART are largely reaped with
high ART coverage at CD4B350/ml. Expanding circumcision coverage first is most cost effective, and then scaling up ART under current
Track D Social Science, Human Rights and Political Science
guidelines is more cost-effective for preventing HIV infections than
scaling up TasP.
WEAD0302
Total Control of Epidemic (TCE) program of Humana People
to People: a community driven response to the fight against
AIDS
M. Lichtenberg1, I. Hansen2 and S.M. Mukhopadhyay3
1
Humana People to People / Planet Aid, Inc., International
Partnerships, Elkridge, United States. 2Humana People to People,
HQ, Shamva, Zimbabwe. 3Humana People to People India (HPPI),
New Delhi, India
Presenting author email: marie.lichtenberg@gmail.com
Background: The Total Control of Epidemic (TCE) Program of Humana
People to People aims to reduce spread of HIV and its impact by
systematically engaging individuals and communities to take control
of their own risk factors, while increasing access to prevention,
treatment and support services. Implemented in close partnership
with respective Ministries of Health and National AIDS Councils
across Sub-Saharan Africa and Asia, TCE has made major impact in
HIV control.
Methods: The TCE model works through two primary strategies:
a) Individual HIV Counselling to Prevent New Infections: Every person
in target areas was provided with counselling for behaviour change
and was assisted to develop individual risk reduction plans. Homebased testing consistent with country guidelines was conducted as
an integrated part of the process.
b) Community Mobilization to Change Social Norms: To change
social norms across the full range of HIV related issues (stigma,
discrimination etc.), community-wide mobilization was carried
out with local leaders, activists, PLHIV to project them as role
models for others along with intensified promotion of existing
services.
Results: Since the first TCE pilot in Zimbabwe in 2000, 11 million
people were covered in 11 countries. 28 million individual HIV
counselling sessions were delivered. As a result, 2 million people
were tested for HIV and received their results. Over 500,000 women
attended PMTCT services. More than 600,000 community activists
were trained and engaged in community mobilization activities. In
Blantyre District of Malawi, 4 times increase of PMTCT utilization
within 3 years and in Ehlanzeni District of South Africa, 6 times
increase of PMTCT utilization within 4 years after TCE implementation
were observed.
Conclusion: With an average cost of U$ 2/person/year, the TCE
model represents a cost effective community-based intervention for
HIV control and care with proven results, that should be replicated
across the most HIV affected countries.
WEAD0303
Phenomenal woman: the development of a program with
the dual goals of HIV and substance abuse relapse
prevention
C. Irizarry1, C. Jones1, C. West2, B. Adjei3 and D. Nordlund1
1
Greenhope Services for Women, INC, New York, United States.
2
Sankofa Services, Atlanta, United States. 3Independent Evaluation
Consultant, Rockville, United States
Presenting author email: cacwest@bellsouth.net
Background: Traditional HIV Prevention Programs have not adequately addressed the issues of women in substance abuse recovery.
163
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
In response, Greenhope Services for Women, Inc developed
‘‘Phenomenal Woman’’, an HIV prevention program for women
recently released from prison and/or mandated to receive residential
substance abuse treatment.
Methods: The target population for ‘‘Phenomenal Woman’’ is
African-American and Latina women demonstrating relatively high
HIV risk behaviors receiving residential substance abuse treatment
at Greenhope. The development of ‘‘Phenomenal Women’’ involved
incorporating key components from ‘‘SISTA’’, other HIV prevention
programs, the ‘‘Helping Women Recover’’ curriculum, and newly
created components. Formative research including: three focus
groups, one key informant interview and two pilot cohorts were
conducted to identify and pretest curriculum components and
participant retention strategies.
Results: ‘‘Phenomenal Woman’’ is comprised of 5 group sessions and
a booster session held 45 days after program completion. Its primary
aims include: enhancing women’s sense of self, increasing HIV/STI
knowledge, as well as attitudes, self-efficacy, and behaviors related
to sexuality, safe and sober sex practices, and spirituality. Utilizing
the formative feedback received (n 42 participants), the program
creatively uses tangible objects (music, affirmation sheets, and
meditation rocks) to reinforce the key messages of strength,
resilience, and making healthy decisions regarding safe and sober
sex behaviors. The program was implemented with 76 participants
with retention rate of 100% across the five initial sessions and 72% at
the booster session.
Conclusion: Greenhope’s ‘‘Phenomenal Woman’’ is an example
of effectively developing and delivering curricula through the
adaptation of evidence-based curricula and the creation of new
components to address a target population’s needs for HIV prevention and substance abuse relapse prevention. Through high
levels of administrative support, participant retention rates were
maximized. Accordingly, ‘‘Phenomenal Woman’’ holds considerable
promise for dissemination to other agencies with similar target
populations.
D2 - Behaviourial and social research on
risk reduction interventions
TUAD0302
HIV prevention needs of transgender sex workers in
Serbia
D. Ilic
Association against AIDS - JAZAS, Belgrade, Serbia
Presenting author email: drilic@sezampro.rs
Background: Research among transgender persons is rare in
Serbia. The emergence of HIV infection led to an increase in
stigma and discrimination, but not to an increase in professional
interest. Sex work in Serbia is illegal and sex workers are
highly discriminated against, especially those of ‘different sexual
orientation’.
This paper presents research of HIV prevention needs of transgender sex workers in Serbia. The research study is meant to be a
baseline study for designing special prevention strategies for this
population group.
Methods: By snowball sampling methodology, 250 sex workers were
incorporated into the research study, of those 40 were transgender,
55 male and 155 female.
Results: A high level of multiple stigmatization and marginalization
is the result of a combination of the following characteristics:
Track D Social Science, Human Rights and Political Science
gender, ethnicity (mainly Roma), very low education levels and high
levels of auto-stigma. Moreover there is a statistically significant
difference between transgender sex workers and male/female sex
workers in terms of being victims of violence much more frequently,
perpetrated by their peers, clients, police and citizens. Transgender
persons differ also in terms of low levels of prevention knowledge,
the presence of misconcepotions about HIV and inadequte assessments of risk to themselves.
Clearly, the preventive needs of this group cannot fully be
met through programs designed for sex workers in general
(such as outreach work, drop-in centers, mobile medical units,
etc).
Conclusion: It is necessary to develop additional preventive strategies, such as:
- Behavior Change commmunication interventions, which
are aimed at increasing self-efficacy, self-confidence which
should result in an increase in visibility and affirmation of
the transgender identity.
- raising public awareness about human rights regardless of
gender differences.
- education of health care workers about the needs of this
group.
WEAD0301
Behaviour change and associated factors among female sex
workers in Kenya
J. Nyagero1, S. Wangila2, V. Kutai2 and S. Olango2
1
Africa Medical and Research Foundation, Health Programmes
Development Directorate, Nairobi, Kenya. 2AMREF, Nairobi
Kenya
Presenting author email: josephat.nyagero@amref.org
Background: Initiatives aimed at behaviour change of key populations such as the female sex workers (FSWs) are pivotal in reducing
the transmission of HIV. A 5-year implementation research to
establish the predictor factors of behaviour change among FSWs in
Kenya was initiated by the African Medical Research Foundation
(AMREF) with Sida and DfID support, whose follow up results are
presented in this paper.
Methods: This cross-sectional survey interviewed 156 female sex
workers (FSWs) identified through snowball sampling. The measurement of behaviour change was based on: the consistent use of
condoms with both regular and non regular clients, reduced number
of clients, routine checks for STIs, and involvement in alternative
income generating activities. The adjusted odds ratios at 95%
confidence interval computed during binary logistic regression
analysis was used to determine the behaviour change predictor
factors.
Results: Most FSWs (84%) had participated in AMREF’s integrated
intervention programme for at least one year, with 4.4 years as
the average duration. The results indicated that 59.1% had gone
through behaviour change during the project’s life cycle. The
adjusted odds ratio showed that the FSWs with secondary education
or more were 2.23 times likely to change behaviour, protestants
were 4.61 times, being in sex work for4 years were 2.36 times,
FSWs with good HIV prevention knowledge were 4.37 times, and
those engaged in alternative income generating activities were 2.30
times more likely to change their behaviour compared to respective
counterparts.
Conclusion: Behaviour change among FSWs was possible and is
associated with the level of education, religious affiliation, number
164
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track D Social Science, Human Rights and Political Science
of years in sex work and one’s level of HIV prevention knowledge.
A re-orientation on the peer education programme to focus on HIV
preventive measures beyond use of condoms is emphasized.
M.A. Bekalu1,2 and S. Eggermont1
1
Katholieke Universiteit Leuven, Belgium, School for Mass
Communication Research, Leuven, Belgium. 2Bahir Dar University,
Bahir Dar, Ethiopia
Presenting author email: mesfiab@yahoo.com
WEAD0304
Background: Given their epidemiological and socio-ecological differences, urban and rural contexts may require differently designed
prevention messages. Utilizing messages framed in terms of the
benefits (gains) or costs (losses) associated with a particular HIV/
AIDS-related behavior could be one viable strategy to address
urban-rural differences.
Methods: Based on relevant literature, urbanity vs. rurality, experience with HIV testing and concern about and information needs on
HIV/AIDS were tested as moderators of framed HIV testing messages’
effectiveness. Gain- vs. loss-framed brochures were distributed
to 394 participants (199 Urban: 46.2% male, 53.8% female; 195
Rural: 79% male, 21% female). Through pretest-posttest measures of
intention to test for HIV, the relative persuasiveness of gain- and
loss-framed messages was determined.
Results: Urbanity vs. rurality, experience with HIV testing and concern
about and information needs on HIV/AIDS significantly moderated the
effects of gain- vs. loss-framing on Intention to Test for HIV, F(1,
385)9.28, pB0.01, n2.02; F(1, 385)17.20, pB0.001, n2.04;
and F(1, 385) 18.97, p B0.001, n2.05, respectively. While urbanites, participants with more experience with HIV testing and those
with higher concern about and information needs on HIV/AIDS were
motivated by gain-framing, ruralites and those with lower concern
about and information needs on HIV/AIDS were motivated by lossframing. Both gain-framing and loss-framing led to similar outcomes
among individuals with low levels of experience with HIV testing, with
a slight advantage for the loss-framed message.
Conclusion: Urbanites and ruralites are motivated by differently
framed prevention messages. It was also noted that to the extent
recipients are concerned about HIV/AIDS and are familiar with HIV
testing, gain-framing is more advantageous, suggesting a possible
construal of HIV testing as more of a prevention than a detection
behavior in such situations.
Determinants of condom use in South Africa
G. Matseke1, L. Simbayi2, N. Wabiri1 and N. Ncitakalo2
1
Human Sciences Research Council, Pretoria, South Africa. 2Human
Sciences Research Council, Cape Town, South Africa
Presenting author email: gmatseke@hsrc.ac.za
Background: Condom use as a means to prevent HIV infection has
significantly increased over the past decade among all age groups in
South Africa. However, little is known about what motivates the
behaviour in South Africa. This study investigated the prevalence and
demographic, psychosocial, and behavioural determinants of condom use among people aged 15 years and older in South Africa who
were sexually active over the 12 months prior to the survey.
Methods: Data from the 2008 national HIV population-based survey
was used. This was a cross-sectional survey which was conducted
using a multi-stage stratified sampling approach. Univariate analysis
and multiple logistic regression were used to identify factors
associated with condom use at last sexual intercourse. A total of
5072 respondents, 46.0% males and 54.0% females, who indicated
having had sex in the last 12 months were involved in the study.
Results: Overall, there was no gender difference found in condom
use: males (64.6%) vs females (60.4%). The multiple logistic regression analyses indicated that youth aged 1524 years and students’
learners were more likely to use condoms at last sex. (AOR2.2528,
AOR2.4358, pB 0.05). Whites, Coloureds and Indians were less
likely than Africans to use condoms (AOR 0.2125, AOR0.3000,
AOR0.4511, pB 0.05). Likewise, married people and those whose
current relationships exceeded a year were less likely to use
condoms (AOR 0.2782, AOR0.3239, p0.00). Finally, having
only one regular sexual partner significantly reduces the odds of
condom use (AOR 0.2855, p 0.021).
Conclusion: It is important to understand more about the nuances of
condom use so that programmes can target those at greatest risk of
infection such as African adults and people in stable relationships,
especially those that might also be involved in other risky behaviours
such as multiple concurrent sexual relationships.
THAD0301
Framing HIV testing messages for urban and rural
audiences: evidence from field experiment in northwest
Ethiopia
Table 1.
THAD0302
‘AIDS is gone. That’s what they think’ College and university
youth in Botswana share their thoughts on HIV, risk,
behaviours, needs and interventions
M. Godwaldt
World University Service of Canada, Gaborone, Botswana
Presenting author email: melissa@wusc.co.bw
Background: Botswana’s HIV prevalence is 17.6% among the general
population and the incidence rate is 2.9%. In 2009, Botswana’s
Zero-order bivariate correlations
Variable
Gain vs. Loss Treatment
Urbanity vs. Rurality
1
2
3
4
5
6
.653**
1
1
.000
1
Baseline Intention to Test for HIV
.040
.241**
Post-intervention Intention to Test for HIV
.049
.201**
.880**
1
1
Concern about & Information Needs on HIV/AIDS
.228**
.612**
.239**
.239**
Experience with HIV Testing
.142**
.624**
.405**
.399**
1
**Correlation is significant at the 0.01 level (2-tailed).
165
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Table 2.
Track D Social Science, Human Rights and Political Science
FRLBD01
Regression Coefficients
Gain
Parameter
B
Effect of a national social cash transfer program on HIV risk
behavior in Kenya
Loss
SE
B
.041 .065
.037 .076
Gain vs. Loss
Urbanity vs. Rurality
.065
.119*
Baseline Intention to Test for HIV
.950** .029
Concern about & Information
.100** .029 .085*
SE
.041
.052
.950** .029
.031
Needs on HIV/AIDS
.180** .038 .034
Experience with HIV Testing
.036
G/L X Urbanity vs. Rurality
.195*
G/L X Concern about & Info
.185** .042
.185** .042
Needs on HIV/AIDS
G/L X Experience with HIV Testing .214** .052
.214** .052
.064
.195*
.064
Tertiary Education Council, recognizing that HIV interventions for
College/University (tertiary) students were few/fragmented, conducted a study to understand student behaviours, needs and gaps
in services. Born in the 1990s, this generation of youth is the first of
its kind-a generation who has grown up with HIV-infected, heavily
affected and message-fatigued.
Methods: Between 20092010, TEC conducted a study of 10% of
tertiary students using self-administered surveys (N 4312). Classes
were randomly selected from 32 institutions and surveys were
augmented by 28 post-survey FGDs. Participation was voluntary,
anonymous and counselling was offered. Survey questions were
qualitative and quantitative.
Results: 57.0% of participants were female and 63.0% were aged
2024. HIV knowledge was high (over 90% responded correctly to
9/11 knowledge questions) but satisfaction with current HIV
interventions was low (44.9%) and 38.5% said condoms are never
available on campus. 82.5% were sexually active and 45.0% had
already engaged in unprotected sex. 53.9% knew their HIV status and
49.4% knew their partner?s status. 33.7% reported that they were
engaging in MCP. Key findings from the FGDs include: a) campuses
are sexualized spaces b) students are involved in transactional
relationships c) students do not perceive themselves to be at risk for
HIV and d) campus interventions are few and irrelevant.
Conclusion: Irrespective of increased knowledge and impact from
AIDS deaths within their families while they were young children,
the sexual practices that gave rise to the current HIV epidemic in
Botswana persist among tertiary youth. The study raises serious
reservations about the assumption that youth are making behaviour
changes. It also exposes gaps in service provision and questions the
strength and relevance of current interventions to youth in a country
with a staggering incidence rate.
Table 1.
Impact
N
S. Handa1, A. Pettifor2, H. Thirumurthy3 and C. Halpern4
1
University of North Carolina-Chapel Hill, Public Policy and Carolina
Population Center, Chapel Hill, United States. 2University of North
Carolina-Chapel Hill, Epidemiology, Chapel Hill, United States.
3
University of North Carolina-Chapel Hill, Health Policy and
Management, Chapel Hill, United States. 4University of North
Carolina-Chapel HillMaternal and Child Health, Chapel Hill, United
States
Presenting author email: shanda@email.unc.edu
Background: Cash transfer programs may reduce the risk of HIV
transmission among young people from poor households by providing economic security. The Cash Transfer for Orphans and Vulnerable
Children (CT-OVC) is the Government of Kenya’s flagship social
protection program, reaching 150,000 poor families with OVC age
17 or below. Households are provided a flat unconditional cash
transfer of US$25 per month. The objective of this study is to assess
whether the CT-OVC reduces HIV related behavioral risk among
adolescents.
Methods: We use data from the third wave of the impact
evaluation of the CT-OVC collected in 2011. The design is a clusterrandomized trial. 1912 households in seven districts across Kenya
were part of wave three; two-thirds were in the program and the
remaining third were randomized out at baseline in 2007. Data on
sexual behavior and other risk related behaviors were collected in
wave 3 only for residents age 15-25. We analyze data for residents
age 21 and below who had not had sexual intercourse at baseline
(N 1516, Females41%). We use multivariate analysis with
controls for age, sex, Nairobi residence, and relationship to household head.
Results: Main study findings indicate that the CT-OVC has reduced
the probability of sexual debut by 6.73 percentage points off a
proportion of 0.37 who had ever had sex after the program began in
2007. This result appears to be driven by males. The program has also
reduced the proportion of adolescents with 2 or more partners in
the last 12 months, by 7.2 percentage points , and reduced the
probability of 2 or more unprotected sex acts in the last 3 months
for females (p0.10).
Conclusion: A large scale, national cash transfer program may
prevent HIV among adolescents by postponing sexual debut, reducing
the number of partners and reducing the number of unprotected
sex acts.
MOPDD0101
A pilot South African worksite-based parenting program:
preliminary effects on parent-child communication about
sex and HIV
Main Results AgeB21
Condom used at
First partner
2partners last
2unprotected sex
Had sex?
Age at first sex
Forced at first sex
first sex
10 years older
12 months
acts last 3 months
0.0673**
1,516
0.121
611
0.0179
594
0.0129
609
0.00978
583
0.0723**
430
0.100
115
Sample is individuals who had not had sex at baseline in 2007. OLS regressions controlling age, sex, Nairobi, child and grandchild of head. All
regressions are linear probability models except for ‘age at first sex’. ‘Impact’ coefficient indicates difference between intervention and control
group. Statistically significant coefficients (PB.10) denoted by **.
166
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Table 1.
Track D Social Science, Human Rights and Political Science
Effects of Intervention on Parent & Child Outcomes
Adjusted Coefficients
Intervention
Intervention
Control
Control
Pre M (SD)
Post M (SD)
Pre M (SD)
Post M (SD)
Comfort Talking to Child about Sex (Parent)
0.98 (0.39), p.20
3.39 (1.84)
5.01 (1.70)
4.07 (2.15)
4.32 (1.91)
Number of Sex & HIV Topics Discussed (Parent)
3.26 (1.12), p.005
7.79 (4.84)
12.38 (4.27)
8.34 (5.75)
9.28 (5.68)
Number of New Sex & HIV Topics Discussed
2.85 (0.80), pB.001
_____
5.91 (4.74)
_____
2.75 (3.58)
Since Baseline (Parent)
Condom Use Self-Efficacy
0.60 (0.21), p.007
3.79 (1.04)
4.57 (0.76)
4.13 (1.00)
4.08 (1.01)
HIV Knowledge (Parent)
.060 (0.32), p .07
6.62 (1.54)
7.32 (1.30)
6.84 (1.95)
6.88 (2.00)
6.32 (1.74)
6.65 (1.86)
6.22 (1.75)
5.72 (2.26)
HIV Knowledge (Child)
0.85 (0.43), p.05
L. Bogart1,2, D. Skinner3, I. Thurston1,2, Y. Toefy3, D. Klein1,
M. Wachman1 and M. Schuster1,2
1
Children’s Hospital Boston, Division of General Pediatrics, Boston,
United States. 2Harvard Medical School, Boston, United States.
3
Stellenbosch University, Tygerberg, South Africa
Presenting author email: laura.bogart@childrens.harvard.edu
Background: In South Africa, adolescents are at high HIV risk, yet few
prevention interventions have been effective. Parents can play a
pivotal role in youths’ healthy sexual development. We tested
whether Let’s Talk!, a pilot worksite-based parenting program,
could improve parent-child communication about HIV and sexual
health.
Methods: A small randomized pilot test was conducted at a large
public worksite in Cape Town. The intervention consisted of five
weekly two-hour group sessions for parents of children aged
1115. Sixty-six parents [64% female, mean age 43 years (SD7),
range 2359] and their 64 children [41% girls; mean age 13 years
(SD1)] completed surveys before and immediately after the
intervention; surveys assessed HIV knowledge, comfort with talking
about sex, communication about 16 HIV- and sex-related topics
(e.g., steps of condom use, how to prevent HIV), and condom use
self-efficacy. Thirty-four Black-African (Xhosa-language) and 32 Coloured (mixed-race; Afrikaans-language) parent-child dyads participated. Thirty-four parents were randomized to one of two
intervention groups stratified by language, and 32 to one of two
control groups.
Results: Multivariate regressions indicated that the intervention
significantly increased parents’ comfort with talking to their child
about sex, b(SE) 0.98 (0.39), p0.02, and the number of sex- and
HIV-related topics discussed with their child, b(SE) 3.26(1.12),
p0.005 (Table 1). Compared to control parents, intervention
parents were more likely to discuss new sex- and HIV-related topics
that had not been discussed before the intervention, b(SE) 2.85(0.80), pB .001. The intervention also significantly increased
parents’ self-efficacy for condom use, b(SE) 0.60(0.21), p0.007,
and showed marginally significant effects on parent and child
HIV knowledge [b(SE)0.60(0.32), p.066, b(SE) 0.85(0.43), p
0.052, respectively].
Conclusion: Let’s Talk! holds promise for improving parent-child
communication. Open communication about HIV and sex is a critical
first step in educating youth and preventing HIV.
WEPDD0101
The relationship between timing of childhood sexual abuse
and subsequent HIV risky behaviours in severely mentally ill
adults
J. Bendezu1, J. Berger-Greenstein1, M. Richardson2, K. Reid1,
J. Wolfe1, C. Mainville1, J. Bacic3 and S. Brady1
1
Boston University, Mental Health and Behavioral Medicine Program,
Boston, United States. 2Boston University, Psychology, Boston,
United States. 3Boston University, Public Health, Boston,
United States
Presenting author email: jason.bendezu@bmc.org
Background: There is a general consensus that people with severe
mental illness(SMI) are more likely to have a history of childhood
sexual abuse and are at increased risk for HIV. For this study, we
hypothesized that our homeless, mentally ill participants reporting
CSA would be more likely to report current engagement in HIV-risky
behaviors, history of STI’s, and associated psychopathology than their
non-CSA counterparts. Furthermore, we hypothesized that those
who had experienced CSA in early to middle childhood (EMCSA)
would be more likely to report these challenges than those who had
experienced CSA in adolescence (ACSA).
Methods: As part of a NIH-funded RCT(1R01MH084696-01A2 PI
Brady) primary and secondary prevention trial for adults with SMI
at-risk for HIV transmission, ninety participants were administered
an assessment battery which included the Structured Clinical Interview for DSM-IV, Demographic Inventory, and Timeline Followback.
Chi-square analyses were used to test our hypotheses and analyze
the relation between our variables of interest.
Results: There were no significant differences in current HIV-risky
behaviors between CSA/non-CSA participants nor for EMCSA/ACSA
participants. However, CSA participants were more likely to present
with PTSD{x2(1, 90)12.95, p B.001}, ASPD{x2(1,90) 13.78, pB
.001}, and prior Chlamydia diagnosis{x2(1,90) 8.46, p B.01} than
non-CSA participants. Also, a trend showed that EMCSA participants
were more likely to report current PTSD symptoms{x2(1,90) 2.73,
p B.10} than ACSA participants. Interestingly, EMCSA participants
were more likely to report being HIV positive{x2(1,45) 4.82,
p B.05} than ACSA participants.
Conclusion: CSA was associated with an increased likelihood of
presenting with associated psychological sequelae and STI’s, namely
Chlamydia. Further, EMCSA participants were more likely to present
with HIV disease than AMCA participants. Our research contributes
to literature outlining the pernicious impact CSA has on physical
and mental health in the severely mentally ill homeless population.
Future studies should identify potential moderators of the CSAhealth risk relationship (e.g., gender).
WEPDD0303
Street-based adolescents: actual emphasis on HIV
prevention
167
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
O. Sakovych1, O. Balakireva2 and T. Bondar2
1
UNICEF Ukraine, Kiev, Ukraine. 2Ukrainian Institute for Social
Research after Olexandr Yaremenko, Kiev, Ukraine
Presenting author email: osakovych@unicef.org
Background: The numbers of street children vary from 30,000 to
100,000 in Ukraine. Their vulnerability to health-related risks, including HIV/AIDS, substance and drug abuse, was a subject of the baseline
study in 2008. Based on its findings, UNICEF implemented a comprehensive approach to HIV-service delivery in four pilot cities and
repeated the survey to assess the effectiveness of interventions in
2011.
Methods: Behavioral survey among street-based adolescents
(N 805, age 1019, 565 boys, 240 girls) was conducted using
location-based network and convenience sampling. Data were
disaggregated by age and gender. Comparative data analysis was
applied to learn the behavioral and knowledge changes. The client
satisfaction questionnaire was used to define the service access
barriers.
Results: Street adolescents are highly vulnerable to HIV-infection:
22% injected drugs, 65% of girls provided commercial sex services;
7% of boys had sex with men; only 13% always used condom with
casual sexual partners. Social vulnerability factors hinder access to
medical and social services: two-thirds of respondents didn’t have a
permanent place of residence and were not covered by medical
services. 46% didn’t have an ID, 54% didn’t have an education
certificate. The piloted interventions caused the positive behavioral
change and knowledge increase: a share of those, who correctly
identified the ways of HIV transmission, has increased for 10%; a
share of those, who were tested for HIV during the last year and
received the result, has almost doubled. The biggest increase in HIVtesting is among girls: every sixth tested in 2008, every third in 2011.
Conclusion: Study confirmed effectiveness and sustainability of
implemented interventions and suggested a roll-out-strategy to the
country. This is of critical importance as a significant number of
street children remains uncovered by services and has a low level of
knowledge about HIV/AIDS, HIV-service organizations and places,
where support is provided and testing is available.
D3 - School-based sexuality education,
life skills, gender equality education
THAD0304
Gender and HIV/AIDS education in the multi-cultural
context of schools at Kakuma Refugee Camp in Kenya
R.M. Ochieng
Kenyatta University, Educational Foundations, Nairobi, Kenya
Presenting author email: rubaimandela@yahoo.com
Background: This study investigated how gender, multicultural and
multi-religious factors influenced the teaching and learning of HIV/
AIDS education.
Methods: The qualitative case study utilised 6 primary schools from
Kakuma Refugee Camp and its host community. The sample had 617
respondents from 9 nationalities, including 356 male and 160 female
pupils. Interviews, observation, FGDs, documentary analysis and
drawings generated data. The research proposal and tools underwent
ethical review.
Results: Cultural and religious tendencies of same gender clustering
denied Muslim Somali pupils an opportunity to work together as
partners in addressing pertinent and effective strategies in HIV/AIDS
education. Unlike the Christian Turkana and Ugandan girls who
Track D Social Science, Human Rights and Political Science
seemed open and outgoing in HIV/AIDS education activities, Somali
and Ethiopian Muslim girls remained quiet, reserved and shy as a
way of showing respect to the male, a behaviour that jeopardised
HIV/AIDS education. Christian Sudanese and Turkana boys and girls
interacted more freely, hence learnt better. Gender influenced
perceptions of pupils on HIV/AIDS education content and pedagogy.
While boys seemed vocal, uncontrolled and eager to discuss sex and
condoms, girls preferred discussing love and care of people living
with HIV/AIDS. Refugee boys produced culturally and linguistically
diverse resource materials that were easily understood across the
cultural groups while portraying males as innocent victims and
females as potentially responsible for the spread of HIV. Notably,
pupils received different and conflicting messages on similar topics
depending on the teacher’s religious background. While older
teachers were perceived as ‘parents’, young male teachers were
seen as having a hidden ‘sex agenda’.
Conclusion: In conclusion, gender, culture and religion, influence the
learning of HIV/AIDS education in refugee schools in a complex
manner, which if not understood and controlled could have negative implications. The study recommends pre-service multicultural
teacher education and training on how to make HIV/AIDS education
gender-responsive.
THAD0305
Uncomfortable silences: narratives of four educators
teaching about HIV/AIDS in a high school near Montréal
M.-A. Cobbler
Concordia University Education, Educational Studies Program,
Montreal, Canada
Presenting author email: ma.cobbler@gmail.com
Background: From 2005, the Québec Ministry of Education cut what
was five (5) hours of sex education (STIs, HIV/AIDS, gender, sexual
diversity, etc.) per year from the secondary school curriculum.
Consequently, in the context of the education reform, teachers
holding specializations in English and Art, Science & Technology and
Moral and Religious Education were persuaded to integrate sexuality
in their course.
Methods: Being highly sexualized sites, high schools act as a channel
for sexual initiation and exploration. Thus, teachers can be catalysts
to providing valuable and life altering information around HIV/AIDS
to their students. Through a qualitative case study, teacher narratives
were collected to identify their classroom structure; strategies;
awareness of HIV/AIDS; and the challenges encountered when discussing the subject in their classroom. Overall, implicating communication processes were an essential factor in uncovering the subtle,
yet, uncomfortable silences found in this study.
Results: The surface-level understanding around HIV/AIDS and a lack
of consistent training and access to accurate resources identified how
teachers understood and valued HIV/AIDS information. Ultimately,
such familiarity corresponded to how their students comprehended
the virus and viewed the marginalized communities most affected.
Conclusion: Theoretical frameworks connected to Paulo Freire’s
Engaged Pedagogy and Nel Noddings’s Pedagogy of Care, were
considered as tools for empowering teachers when imparting
knowledge on HIV/AIDS.
THAD0306
Rethinking the ‘teacher’ in school-based, teacher-led
sexuality education programmes in rural and urban
Tanzania
168
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
D.J. Matungwa1, C. Chenha2, J. Kachuchuru2, T. Visser3, M. van
Reeuwijk3, G. Maro4, A. Massawe5, I. Kalongola6, J. Francis2,
J. Changalucha2 and G. Mshana2
1
National Institute for Medical Research, 28, United Republic of
Tanzania. 2National Institute for Medical Research - Mwanza Centre,
Mwanza, United Republic of Tanzania. 3Rutgers World Population
Fund, Utrecht, Netherlands. 4African Medical and Research
Foundation, Tanzania, Dar es Salaam, United Republic of Tanzania.
5
Health Actions Promotion Association, Tanzania, Singida, United
Republic of Tanzania. 6Restless Development, Iringa, United Republic
of Tanzania
Presenting author email: matungwa@gmail.com
Background: School-based, teacher led Sexuality Education (SE) is
effective in promoting and protecting young people’s sexual health.
In sub-Saharan Africa, much of SE is provided through school-based,
teacher-led programmes. The aim of this study was to find out what
topics in Comprehensive Sexuality Education (CSE) were acceptable
and not acceptable to the teachers.
Methods: This study was part of an assessment of the status of
Sexual and Reproductive Health and Rights in three regions (Tanga,
Singida and Iringa) in Tanzania. Respondents were purposively
obtained from 6 purposively selected primary and secondary schools
in three purposively selected wards. A total of 45 teachers participated in Focus Group Discussions and Group Interviews. Data were
analyzed using Nvivo software.
Results: Six topics in CSE were consistently rejected by teachers.
These are homosexuality, masturbation as an alternative to sexual
intercourse, condom use, sexual pleasure and enjoyment, sexual
behavours other than intercourse and appropriate and inappropriate
touching. Three major reasons were given to why they rejected these
topics. First, they explained that if students are taught about these
topics, they may practice them and that would fuel sexual activity
among them. Second, since they have to teach practically, teachers
explained that demonstrating these topics would be an embarrassment to them and to the students. Third, they reported that these
topics are against sexual norms of the communities where they
(teachers) and students come from.
Conclusion: With these findings, it is important to rethink the
position of teachers in the delivery of CSE. Being ‘‘teachers’’ does not
exclude individuals from abiding by sexual norms of their community.
The rejection of these topics indicates that teachers still adhere to
sexual norms of their communities. In order to strengthen CSE
programmes, programmes need to work on sexual norms that may
hinder the delivery and success of CSE in schools.
D4 - Community, social and political
mobilization and building of social capital
THAD0303
Promoting sexual and reproductive health (SRH) in
adolescent girls through traditional initiation in the coast
region of Tanzania
A. Itaka and M. Makokha
FHI 360, UJANA Project, Dar es Salaam, United Republic of Tanzania
Presenting author email: aitaka@fhi360.org
Background: Coastal people of Tanzania practice a rite of passage
(unyago) for girls when they enter puberty (wali). Unyago is
conducted by respected, mature women (manyakanga) who use
local art forms and idioms to address family life and sex education.
Track D Social Science, Human Rights and Political Science
Pre-training test
Post-training test
Score
Score
Persons
Difference (/)
Persons
4
100%
12
8
50%
17
50%
14
3
B50%
7
B50%
2
5
100%
Pre- and post-training differences.
Unyago is sometimes faulted for encouraging early sex, teenage
marriage, early child-bearing, and multiple concurrent partnerships
(MCP).
Methods: We conducted a participatory learning-and-action exercise
with manyakanga in the Coast region. We assessed: 1) manyakanga’s
knowledge of SRH and 2) manyakanga?s potential to serve as
promoters of SRH. In 2011, 28 manyakanga (who were involved in
small-scale pilot activities since 2008; about 50% of the manyakanga
at the program sites) received a five-day training. PAYODE (a
community-based organization) conducted eight monthly forums,
and FHI 360 provided 28 person-days of on-site technical assistance.
Results: Training improved manyakanga’s knowledge of SRH.
Eight months after training, manyakanga had initiated 450 wali
(about two girls per manyakanga per month). Parents, elders and
non-program manyakanga who were initially suspicious of the
modified unyago reported a preference for it. Pregnancy, MCP and
school withdrawals are less common among wali who have been
in the program. All-night celebrations for wali (associated with
alcohol, drug use and sex) have been discontinued in the program
areas.
Conclusion: Harmful aspects of a traditional practice can be modified
to promote positive behavior. Training and advocacy that involves
community leaders (such as manyakanga) can produce a sustainable
system of effective change agents. The modification of socio-cultural
norms should be locally appropriate, incorporate the purpose and
beneficial aspects of a practice, demonstrate added value, and be led
by custodians of that practice.
TUPDE0105
Social capital and AIDS competent communities: evidence
from eastern Zimbabwe
C. Campbell1, M. Nhamo1, C. Nyamukapa2,3, C. Madanhire2, K. Scott4,
M. Skovdal5, L. Sherr6 and S. Gregson2,3
1
London School of Economics and Political Science, London, United
Kingdom. 2Biomedical Research and Training Institute, Harare,
Zimbabwe. 3Imperial College London, School of Public Healh,
London, United Kingdom. 4Johns Hopkins Bloomberg School of Public
Health, Baltimore, United States. 5University of Bergen, Department
of Health Promotion and Development, Bergen, Norway. 6University
College London, Department of Infection and Population Health,
London, United Kingdom
Presenting author email: l.sherr@ucl.ac.uk
Background: Interpersonal communication has been implicated as a
key factor in HIV declines in Zimbabwe (Halperin et al., 2011), but little
is known about the social networks through which it might have taken
place. In the quantitative component of a World Bank sponsored
study, Gregson (2012) found associations between community group
memberships and HIV avoidance. Our qualitative component elaborates on these findings through mapping out possible psycho-social
pathways between group participation and more effective community
responses to HIV/AIDS.
169
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Methods: We used Nhamo’s (2010) conceptualisation of the ‘HIV
competent community’ to frame thematic analysis of the Manicaland
Project’s qualitative dataset. 481 people participated in 30 children’s
draw-and-write, 100 interviews and 55 focus groups exploring local
responses to HIV/AIDS. These included people on ART; healthcare
workers; workers; community group members; sex workers and
clients; and participants in cash transfers, home-based care, support
groups and peer education.
Results: Community group memberships are often associated with
lower HIV incidence amongst women, and higher incidence amongst
men. Group memberships impact directly through facilitating or
hindering healthy behaviours, and indirectly through impacting service
access, and the effects of peer education, home-based care and cash
transfers. Gendered group communication styles often make women
more likely to engage in positive health-related dialogue, and to
entrench macho stereotypes and health-damaging behaviours in men,
although this is not always the case.
Conclusion: Growing evidence suggests indigenous community
groups could become a useful focus for enhanced HIV/AIDS
prevention, care, treatment and impact mitigation. Efforts might
focus on enhancing the beneficial effects of groups (mostly on
women) and limiting their damaging effects on men. Parallel efforts
should facilitate contexts that are supportive of beneficial group
effects, including a wider comprehensive response with empowering
support from funders and community partnerships with supportive
service providers.
WEPDD0301
Reducing children’s vulnerability in a regions with HIV
prevalence with an integrated livelihoods, protection
and psychosocial support (PSS) package
C. Kiiza1 and A. Babu Ndyabahika2
1
WEI/Bantana Uganda, Kampala, Uganda. 2Initiative for AIDS
Oprhans & Vulnerable Children, Kampala, Uganda
Presenting author email: christinebantwana@gmail.com
Background: In Western Uganda, high HIV prevalence, poverty, and
abuse/exploitation threaten children’s wellbeing and can contribute
to high HIV transmission risk for vulnerable children. A comprehensive approach is needed to address the key drivers of vulnerability
and improve child welfare for highly vulnerable children. World
Education (WEI)’s Western Uganda Bantwana Program (WUBP)
builds the capacity of nine community-based organizations (CBOs)
to provide comprehensive services and referrals strengthening to
3,100 vulnerable children and their families to improve child welfare.
Methods: Using the following methods, Bantwana and local partners
gathered evidence suggesting that an integrated package of psychosocial support (PSS), livelihoods, and child protection (CP) interventions can effectively contribute to reducing child vulnerability and
improve children’s overall wellbeing:
Child profiling baseline and follow-on survey: of 132 children,
measuring child wellbeing across a range of internationally
accepted vulnerability indicators;
CP case study: focus group discussions with districts, children,
schools, and other protection stakeholders to assess school and
community child protection interventions;
PSS assessment: interviews/focus group discussions with
volunteers, caregivers, CBO partners and children, exploring
effects of a household approach to PSS on child wellbeing; and
Qualitative evaluation study (with Columbia University):
of 247 households, to determine benefits of livelihoods/
protection interventions on child wellbeing.
Track D Social Science, Human Rights and Political Science
Results: Preliminary results from the Columbia study suggest that an
integrated protection/livelihood intervention can improve outcomes
in child wellbeing. The CP case study and PSS assessments reveal that
strengthening linkages among CP stakeholders (school, community,
government and household)*improves child protection outcomes,
while the child profiling survey reinforces the importance of a
household approach.
Conclusion: Preliminary evidence suggests that an integrated package
of PSS, livelihoods, and CP intervention may reduce vulnerability and
improve child wellbeing which could have implications for HIV
prevention approaches for vulnerable children in regions with high
HIV prevalence.
THPDC0206
Increasing transgender community capacity to impact
HIV prevention and health care services: Coalitions
in Action for Transgender Community Health (CATCH)
D. Castro1,2,3, J. Keatley1,2,3, L. Gutierrez-Mock1,2, J. Sevelius1,2 and
G. Rebchook1,2
1
Center of Excellence for Transgender Health: University of California,
San Francisco, United States. 2Center for AIDS Prevention Studies:
University of California, San Francisco, United States. 3Pacific AIDS
Education and Training Center: University of California, San Francisco,
United States
Presenting author email: danielle.castro@ucsf.edu
Background: The Center of Excellence for Transgender Health
(CoE) has been mobilizing transgender (trans) community throughout the United States utilizing a coalition building approach since
2007. The CoE along with its National Advisory Board (NAB) has
identified and supported community leaders, health departments
and key stakeholders in engaging the transgender community,
identifying gaps and developing strategies for addressing identified
unmet needs in the U.S. The CoE supports local community efforts
in organizing conferences, symposiums, and summits that are
focused on transgender specific health and well being.
Methods: In the CATCH model, with support from staff of the
CoE, local coalitions guide the community mobilization process
and lead data collection and analysis efforts, prioritize HIV prevention
and health care needs, develop a comprehensive plan to strengthen
community access to and utilization of HIV prevention and health care
services, and decide how to evaluate these efforts.
Results:
Community mobilization is a very empowering process that
can provide participants with a sense of control, self esteem,
self determination and increased capacity for changing systems
to be transgender inclusive.
Both providers and community members are able to create
meaningful, sustainable linkages for capacity building and
increasing access to services.
Social networks created through CATCH are sustainable and
increasingly multiplying.
CATCH is a groundbreaking national network that ensures
that community members have a voice in the transgender
HIV and human rights movement through a coordinated
effort.
Conclusion: CATCH increases transgender community capacity to
access services by supporting advocacy efforts, creating networking
opportunities, and increasing visibility of trans HIV prevention and
health care needs.
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track D Social Science, Human Rights and Political Science
1
D7 - Child care, infant feeding,
pre-chewing of food (premastication)
MOPDD0303
Determinants of infant feeding intent and appropriateness
of choices for formula feeding in the Djoungolo Prevention
of Mother-To-Child Transmission of HIV programme,
Yaounde, Cameroon
A.E. Njom Nlend1, B. Bagfegue Ekani2, A. Tchouamo2, A. Mbi3 and the
Mother & Child Djoungolo Network
1
National Social Insurance Fund Hospital, Pediatrics, Yaounde,
Cameroon. 2National Social Insurance Fund Hospital, Yaounde,
Cameroon. 3Association Camerounaise d’Aide aux
Personnes et Familles Affectées par le SIDA, Yaounde,
Cameroon
Presenting author email: anne.njom@gmail.com
Background: The dilemma of infant feeding in HIV context of poor
resource setting remains unresolved and the practice of replacement feeding may happen to be a curse by lowering child survival.
Appropriate infant feeding counseling can reverse such risk as well
as limiting spill-over (WHO, 2010.)
Objective: to describe infant feeding intents of HIV positive women
and determine the appropriateness of choice of those opting for
formula-feeding after the counseling process.
Methods: Routine infant feeding counseling of HIV positive mother
offered by short-course trained counselors during the pregnancy or
in the early-post partum. Intents were assessed using a generic
acceptable, feasible, affordable sustainable, secure (AFASS) score
composed of 7 variables grading from 0 to 2:type of energy, source
of water, kind of latrines, disclosure to the partner, monthly income,
ability to prepare bottle feeding and to give a reason for non
breastfeeding. An AFASS score above 10/14 was considered as
appropriate for formula feeding.
Results: 950 women were included for cohort characteristic. Among
924 women counseled, 63% intended to formula feed their babies
while 37% planned to breastfeed. The AFASS criteria 10 was met
by 87% who intent to practice formula-feeding compared to 57%
of those who intent to breastfeed. Women counseled during
post-partum were more likely than others to opt for artificial feeding (p B 0.001). Formula-feeding choice was more appropriate in
women counseled during pregnancy vs after delivery (p 0.02).
The determinants of choosing replacement feeding were tertiary
education (p B 0.001), no previous exclusive-breastfeeding, HIVstatus disclosure (p B 0.001) and AFASS score10 (OR: 5; 95%
CI: 36).
Conclusion: in Djoungolo, after infant feeding counseling, replacement feeding intent is mostly appropriate fitting mother’s environment and livelihood. In addition, the desire to breastfeed remains
real as more than 1/2 women who choose to breastfeed met the
conditions to practice formula feeding.
D8 - Prevention with HIV-positive people
WEAD0305
Effect of a values-based prevention curriculum on
HIV-positive couples from four regions in Ethiopia
D. Brewster-Lee1 and M. Suba2
Catholic Relief Services, Baltimore, United States. 2Catholic Relief
Services Ethiopia, Addis Ababa, Ethiopia
Presenting author email: misgina.suba@crs.org
Background: Although evidence reveals that most heterosexual HIV
transmission in sub-Saharan Africa takes place within marriage or
cohabitation, approaches for people living with HIV (PLHIV) focus
primarily on individuals. The Faithful House (TFH) is a couples-based,
skills-building curriculum used with 45,000 couples in twelve countries, recently modified to address PLHIV issues. Research examined
the effect of TFH on attitudes and behaviors to provide evidence for a
couples-based approach for more holistic PLHIV programming.
Methods: Participants, using convenience sampling, from HIV programs in four regions of Ethiopia were randomly distributed between
intervention and control groups.The intervention group participated in
TFH workshop for PLHIV. Both groups completed surveys at baseline
and three months post-intervention which was analyzed using STATA.
Results: The study surveyed 378 individuals with a mean age of
35.2. Most couples (88%) were either married or cohabitating. All
participants had been tested for HIV with 90% testing positive.
Intervention participants (193) reported significant changes (pB
0.01) in the quality of their relationship, including improved communication and joint decision-making about child care, finances and
sexual negotiation. Intervention participants had statistically significant improvements in medication adherence (18% non-adherent at
baseline versus 10% at three-months) and percentage diagnosed with
sexually transmitted infections in the past three months (7.3%
decreased to 4.7%). Of males with pregnant partners, 94% in the
intervention group attended antenatal care visits compared with
36% in the control. Intervention participants also reported statistically significant decreases (p B0.05) in violent behaviors including
insulting, shoving, and forcing sex.
Conclusion: The modified TFH curriculum had a positive impact on
attitudes and behaviors affecting the physical and relationship
health of PLHIV couples. These preliminary results indicate potential
for couples-based approaches for more holistic programming for
PLHIV. Continued evaluations are critical in determining sustained
impact on health status outcomes, attitudes and actual behavior
change.
D9 - Counseling and testing (HIV
counseling and testing (HCT) and
voluntary counseling and testing (VCT)),
social, psychological and behavioral
aspects of HIV testing and counseling
WEPDE0202
Mapping spatial barriers and facilitators to HIV testing by
work environments among sex workers in Vancouver,
Canada
K. Deering1, C. Feng2, O. Amram3, J. Montaner1, J. Chettiar2,
S. Strathdee4 and K. Shannon1
1
University of British Columbia, Medicine, Division of AIDS,
Vancouver, Canada. 2BC Centre for Excellence in HIV/AIDS, Vancouver,
Canada. 3Simon Fraser University, Geography, Vancouver, Canada.
4
University of California San Diego (UCSD), San Diego,
United States
Presenting author email: kdeering@cfenet.ubc.ca
Background: As part of a government-sponsored pilot initiative of
‘treatment as prevention’, recent efforts have been made to improve
171
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
access to HIV prevention and care, including HIV testing, to vulnerable
sub-populations in Vancouver, Canada. This study assessed the
association between geographic factors measuring access to HIV
testing sites and having a recent HIV test among hidden street- and
off-street sex workers(SWs) in Vancouver.
Methods: Baseline data were used, including an intervieweradministered questionnaire, HIV/STI testing and geographic location
data, from an open prospective cohort of SWs recruited in 2010
in Metropolitan Vancouver (‘‘An Evaluation of Sex Workers’ Health
Access’’[AESHA]). Access was measured by density of testing sites
within a catchment surrounding SWs’ place of solicitation (radius
distance travelled in 15 minutes of combined bus/walking) and time
to travel to nearest testing site. Bivariate and multivariable logistic
regression was used to identify if density and time were independently associated with recent HIV testing (in the last year). Adjusted
odds ratios and 95% confidence intervals were reported (AOR:
[95% CIs]).
Results: In total, 291 seronegative SWs from Vancouver City were
included, with 69.4% (202) reporting a recent HIV test. In bivariate
analysis, having a recent HIV test was significantly associated with a
higher density of testing sites (p B 0.001) and time to nearest testing
site (p 0.05). After adjusting for key confounders (recent injection
drug use, age and sexual identity), having a recent HIV test was
significantly associated with increased density of HIV testing sites:
the probability of having a recent HIV test increased by 2% for each
increase in one testing site (1.02[1.011.04]).
Conclusion: Our results highlight the importance of physical availability of HIV testing sites within sex work environments to facilitate
use of HIV prevention and care among SWs. Increased mobile and
safer-environment interventions that facilitate access to voluntary
and confidential HIV testing at outdoor and indoor sex work venues
remain a critical priority.
D10 - Other behavioural, social and
structural interventions, including in the
context of biomedical interventions
WEAD0505
Feasibility, acceptability and initial efficacy of the ‘Unity
workshop’: an internalized stigma reduction intervention
for African American women living with HIV
D. Rao1, M. Desmond2, M. Andrasik1, T. Rasberry3, N. Lambert4,
S. Cohn4 and J. Simoni1
1
University of Washington, Seattle, United States. 2PATH, Seattle,
United States. 3Babes Network YWCA, Seattle, United States.
4
Northwestern University, Chicago, United States
Presenting author email: deeparao@uw.edu
Background: HIV/AIDS is a leading cause of death for AfricanAmerican women in the United States between the ages of 25 and
34 years. Studies have suggested that HIV-related stigma impacts
morbidity and mortality rates because it contributes to poor
treatment utilization for various groups of people with HIV. Despite
these findings, there are no intervention studies investigating
stigma reduction strategies for African-American women living with
HIV.
Methods: We implemented an adapted version of the International
Center for Research on Women’s HIV Stigma Toolkit for AfricanAmerican women living with HIV, with intervention modules
led by an African-American woman living with HIV. Twenty-four
participants attended workshop sessions split across 2 weekday
Track D Social Science, Human Rights and Political Science
afternoons, discussed issues ‘‘triggered’’ by videos that were
produced specifically for the intervention, learned stigma reducing
mechanisms from each other, and practiced using these mechanisms
in role plays. Participants completed a measure of internalized
stigma before, immediately after, and 1-week after workshop
participation.
Results: The intervention demonstrated feasibility and the women
enthusiastically accepted the intervention. The women reported
decreased stigma from the start of the workshop to immediately
after (p 0.05) and 1 week after workshop participation (p 0.07).
Conclusion: Findings suggest that the Unity workshop holds promise
for reducing internalized stigma for African-American women living
with HIV.
MOPDD0105
Effectiveness of psycho-education in a family-to-family
program on family relationships and emotional quotient
of adolescents in HIV families in Thailand
W. Chaitha1, C. Jiraphongsa2, S. Khumthong2, L. Lili3, L. Sung-Jae3,
W. Isaranun4, S. Kaeworasan5, R. Pibulniyom6 and I. Chaitha1
1
Chiangsaen Hospital, Ministry of Public Health, Chiangsaen,
Thailand. 2Ministry of Public Health, Department of Disease Control,
Bangkok, Thailand. 3University of California, Los Angles, Department
of Psychiatry and Biobehavioral Sciences, Los Angles, United States.
4
Maechun Hospital, Ministry of Public Health, Maechun, Thailand.
5
Khonburi Hospital, Ministry of Public Health, Khonburi, Thailand.
6
Parkchong Hospital, Minitry of Public Health,
Parkchong, Thailand
Background: This study examined the effectiveness of psychoeducation in Family-to-Family Project on family relationship and
emotional quotient (EQ) of adolescents in HIV families in two
representative provinces in Thailand, Chiangrai and Nakorn Ratchasima. The intervention included core elements identified by Thai
Ministry of Public Health and University of California, Los Angles, USA
for improving physical and mental health, family relationship, and
social outcomes for HIV-affected families.
Methods: The sample consisted of 194 adolescents (aged 1217
years) in 402 HIV-affected families. A randomized controlled
trial with pre-test and post-test was performed during December
2006 - January 2009. Adolescents were randomly assigned into 2
groups: (a) adolescents whose parent and caregiver(s) attended
psycho-education and (b) adolescents whose parent and caregiver(s)
did not attend psycho-education. The instrument was a set of
questionnaire including: family relationship and EQ. Data were
collected prior to the beginning of the program, and at 24-month
follow-up. They were analyzed using t-test and logistic regression
statistics.
Results: The study findings suggested, when controlled sex, age and
education, family relationship and EQ of adolescents before and
after the intervention in each group did not vary significantly.
Family relationship had significantly positive relationship with
EQ on the ‘‘happy’’ subscale [adjusted Odds Ratio (OR)12.03,
95% Confidence Interval(CI)3.2145.02] and total EQ [adjusted
OR9.57, 95% CI 2.2840.17]. However, it did not relate to
EQ on the ‘‘good’’ subscale [adjusted OR 3.13, 95% CI 0.57
17.12] or the ‘‘competence’’ subscale [adjusted OR1.41, 95%
CI 0.15812.57].
Conclusion: Family relationship is a protective asset in happiness
and total EQ of adolescents in HIV-affected families. However, larger
and robust trials are needed to further determine the effectiveness of psycho-education for Thai HIV families. This study was funded
by the National Institute of Nursing Research (grant NINR R01NR009922).
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track D Social Science, Human Rights and Political Science
WEPDD0102
Home-based mental health services are associated with
improved mental health outcomes among individuals
with HIV
S. Reif1, K. Whetten2, E. Wilson2 and S. Legrand2
1
Duke University, Center for Health Policy and
Inequalities Research, Charlotte, United States. 2Duke University,
Center for Health Policy and Inequalities Research, Durham,
United States
Presenting author email: susan.reif@duke.edu
Background: Mental disorders are highly prevalent among individuals with HIV and are consistently associated with negative health
outcomes. These disorders are often not adequately treated due
to significant individual and community level barriers. Innovative
approaches are needed to engage and effectively treat mental health
problems among individuals with HIV.
Methods: The NIH-funded Collaborative HIV/AIDS Mental Health
Program (CHAMP) assessed the feasibility and preliminary outcomes
associated with providing 9 months of in-home mental health
counseling for 40 individuals with HIV and a Major Axis I mental
disorder living in Mecklenburg County North Carolina. The
CHAMP treatment was guided by the HIV/AIDS Illness Management
and Recovery Model (HAIMR), which was adapted from the
evidence-based Illness Management and Recovery treatment
model using a Community Based Participatory Research approach.
Study participants were surveyed at baseline, 5 and 9 months
to assess psychiatric symptoms (using the Brief Symptom Inventory
(BSI)), social support, coping, and medication adherence.
Results: The CHAMP study participants were reflective of the HIV
population in the region with respect to race (80% African-American)
and gender (35% female).
Statistically significant decreases in the global BSI score and a
number of BSI symptoms dimensions including anxiety, depression,
obsessive compulsive, and hostility were detected. The sample
means for anxiety, hostility, and phobia dropped below the BSI
clinical significance level and the proportion of participants meeting
the BSI case definition based on having a BSI Global Score of 63 or
above decreased from 85% of participants to 54% of participants
(p .018). Statistically significant improvement was also found for
the SF-12 mental health scale, adaptive coping, overall social support
and emotional support.
No statistically significant differences were noted in outcomes by
gender or race/ethnicity.
Conclusion: Findings from the CHAMP Study suggest that inhome mental health treatment may be beneficial in engaging and
treating HIV-positive individuals with co-morbid mental health
disorders.
DEMOGRAPHIC CHARACTERISTICS
Female
35%
African-American
80%
Average Age
43.1
Less than High School Education
28%
PROBABLE MENTAL DISORDERS (Mini-International
Neuropsychiatric Interview (MINI))
Depression
55%
Bipolar
30%
PTSD
38%
Baseline Characteristics of Study Subjects (N 40).
Baseline Survey
Survey at 9
months (after
(prior to
treatment
treatment
completion);
entry)
**pB.01
71.5
65.7**
BSI Depression
BSI Anxiety
68.5
65.8
62.6**
57.6**
BSI Hostility
64.5
57.5**
BSI Phobic
63.1
57.9**
SF-12 Mental Health Scale
37.6
46.5**
2.9
3.2**
57.6
70.9**
17.4%
4.8%
Brief Symptom Inventory
(BSI) Global Score (higher
score indicated higher
symptom levels)
Adaptive Coping (Brief
COPE scale)
Overall Social Support
(Medical Outcomes Study
Social Support Index)
Missed HIV medication in
last 24 hours
CHAMP Study Findings (N 34).
D12 - Socio-economic vulnerability and
stratification (e.g., inequality, poverty,
wealth, social status)
WEAD0102
Critical consciousness, perceived racial discrimination and
perceived gender discrimination in relation to
demographics and HIV status in African American women
G. Kelso1, R. Cruise1, S. Dale1, K. Weber2, M. Cohen2 and L. Brody1
1
Boston University, Psychology, Boston, United States. 2Cook County
Health & Hospital Systems, Chicago, United States
Presenting author email: gkelso@bu.edu
Background: Perceived racial (PRD) and gender discrimination (PGD)
relate to poorer health in African American (AA) women (Kreiger,
1990; Borell et al., 2006). Critical consciousness (CC), the awareness
of social oppression, has been found to moderate the effects of
discrimination stress (Kelso et al., submitted 2012). The present study
explored PRD, PGD, and CC in AA women, examining their relationships to age, education, employment, and HIV status.
Methods: Participants were 98 AA women (73 HIV-positive, 25
HIV-negative) from the Chicago Women’s Interagency HIV Study.
Table 1 displays demographic information. Self-report questionnaires
measured CC and its dimensions Power Discontent, Rejection of
System Legitimacy (RSL), and Belief in the Need for Social Change
(BNSC) on behalf of AAs, and PGD, and PRD. Pearson correlations
examined age, education, employment and HIV status in relation to
CC. Partial correlations examined CC in relation to PGD and PRD. Ttests examined HIV status differences in PGD, PRD, and CC.
Results: HIV-negative women (M4.38, SD.71) endorsed significantly greater (BNSC) on behalf of AAs than HIV-positive women
173
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track D Social Science, Human Rights and Political Science
Variable
Age Education Employment
Identification with Women
.04
.19
.30**
Identification with African
.06
.15
.24*
Americans
Power Discontent
.10
.21*
.20*
Rejection of System Legitimacy
.25*
.22*
.17
.26*
.27**
.29**
.04
.25*
.17
Belief in need for social change on .03
behalf of African Americans
Total Critical Consciousness
Perceived Gender Discrimination
.17
.23*
Perceived Racial Discrimination
.22*
.20
.14
Note. *p B.05, **p B.01.
Critical Consciousness
Dimension
Perceived Gender
Discrimination
Perceived Racial
Discrimination
Power Discontent
.28*
.27**
Rejection of System
.32**
.29**
.31**
.38***
Legitimacy
Total Critical
Consciousness
Note. *p B.05, **p B.01, ***pB.001.
(M 3.83, SD 1.09); t(94) 2.33, p.02). Age significantly related
to higher RSL, PGD, and PRD. Education and employment significantly
related to higher total and subscale CC scores. Table 1 displays correlations. Controlling for demographics, total CC, RSL, and Power Discontent were significantly related to higher PGD and PRD (see Table 2).
Conclusion: Among HIV-positive and HIV-negative African American
women, older age, employment, and more education related to
higher CC. HIV-negative women endorsed greater BNSC on behalf of
AAs. Lower CC related to having fewer material resources and to
having HIV itself, indicating that HIV interventions targeted to raise
CC should also support access to resources such as education and
employment. Higher CC related to higher PGD and PRD, suggesting
that PGD and PRD may be externalized attributions of social inequity
related to awareness of social oppression.
FRLBD02
Freedom to adhere: the complex relationship between
democracy, wealth disparity, social capital and HIV
medication adherence in adults living with HIV
J.C. Phillips1, A. Webel2, C. Dawson Rose3, W.L. Holzemer4,
W.-T. Chen5, M.O. Johnson6, K. Kirksey7, J. Voss8, E. Sefcik9, L.S. Eller4,
I.B. Corless10, D. Wantland4, C. Portillo3, L. Tyer-Viola10,
K.M. Sullivan11, P.K. Nicholas10, S. Iipinge12, K. Nokes13,
J. Kemppainen14, M. Rivero-Mendez15, P. Chaiphibalsarisdi16,
P. Reid14 and J. Brion17
1
University of Ottawa, Faculty of Health Sciences, School of Nursing,
Ottawa, Canada. 2Case Western Reserve University, Frances Payne
Bolton School of Nursing, Cleveland, United States. 3University of
California, San Francisco, School of Nursing, San Francisco, United
States. 4Rutgers University, College of Nursing, Newark, United
States. 5Yale University, New Haven, United States. 6University of
California, San Francisco, San Francisco, United States. 7Seton Family
of Hospitals, Center for Nursing Research, Austin, United States.
8
University of Washington, Seattle, United States. 9Texas A&M
University-Corpus Christi, Corpus Christi, United States. 10MGH
Institute of Health Professions, Boston, United States. 11University of
Hawaii at Manoa, Honolulu, United States. 12University of Namibia,
Windhoek, Namibia. 13Hunter College, CUNY, Hunter Bellevue School
of Nursing, New York, United States. 14University of North Carolina Wilmington, Wilmington, United States. 15University of Puerto Rico,
San Juan, Puerto Rico. 16Suan Sunandha Rajabhat University,
Bangkok, Thailand. 17Duke University, School of Nursing, Durham,
United States
Presenting author email: jcraigarnp@gmail.com
Background: Human rights approaches to managing HIV globally offer
hope to vulnerable persons living with HIV (PLHIV), but structural
challenges impede achievement of this goal. Little is known about the
relationship between structural challenges and health promoting
behavior among PLHIV. Our purpose was to describe associations
between national level democracy ranking, HIV criminalization,
perceived social capital, and antiretroviral therapy (ART) adherence
among an international sample of PLHIV.
Methods: We recruited PLHIV at 16 sites in Canada, China, Namibia,
Thailand, and the United States. Participants (n 2,149) completed a
cross-sectional survey of demographics, social capital, and ART
adherence. Data were collected between August, 2009 and March,
2012. HIV criminalization was assessed by reviewing site specific
state/provincial or national laws and policies. Five aspects of a
country’s democracy and freedom were obtained from the
World Audit (www.worldaudit.org) international database. Data
analysis included descriptive statistics, correlational and regression
analyses.
Results: Participants were primarily male (68%) with an average age
of approximately 47 years. Overall, mean 3-day self-reported ART
adherence was 82.6%. Strong associations were observed between
medication adherence and overall democracy ranking (0.66, pB
0.01) and degree of limitation to political rights (0.68, p B 0.01). In
the final model, overall democracy ranking; HIV criminalization (e.g.,
HIV specific enhancements for other crimes, HIV reporting laws), and
number of HIV-related prosecutions; and total social capital score
were significantly associated with self-reported ART adherence after
controlling for site, gender, age, time since HIV diagnosis, and
adherence self-efficacy (F132.05, p B 0.01, adjusted R2 0.56).
Conclusion: Our results demonstrate the interconnectedness of the
political, social and biomedical spheres in addressing PLHIV health
care needs. Decontextualized biomedical advances and models of
intervention efficacy are insufficient for future HIV management. Our
results provide evidence for the importance of using intersectoral
human rights based approaches to the management of HIV and its
intersecting vulnerabilities globally.
WEPDD0106
When time doesn’t heal: complicated grief among orphans
in rural Zambia
A. Gschwend1,2, K. Wespi1, P. Amman1 and L. Langhaug3
1
Swiss Academy for Development, Biel-Bienne, Switzerland.
2
University of Bern, Institute of Psychology, Section of Social
Pscychology, Bern, Switzerland. 3REPSSI, Harare, Zimbabwe
Presenting author email: lisa.langhaug@gmail.com
Background: Across sub-Saharan Africa, the HIV pandemic has
orphaned millions of children. Evidence from high-income settings
on complicated grief, which precipitates psychologically and medically debilitating symptoms, is growing. However research on how
174
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
orphans in rural Africa cope with their loss remains scarce. We report
on prevalence and predictors of complicated grief among a rural
Zambian cohort.
Methods: 376 rural Zambian orphans 10-18 years, (46.3% female,
44.1% orphaned by AIDS) were interviewed five times. Respondents were included if they had lost their parent(s) at least two years
prior to the final survey. Validated scales from Western settings were
translated and culturally adapted. Complicated grief was defined as
experiencing above average levels of grief symptoms in the last four
weeks. Cross-sectional data assessed prevalence of complicated grief
and tested multiple regression models. Bootstrapping supported
robust regression coefficients estimates.
Results: Approximately one-third (30.3%; n 114) of these orphans
reported complicated grief symptoms. Independent predictors (pB
0.05) included peer bullying, daily stress (e.g. excessive household
chores, looking after ill family) poor primary-caregiver relations,
within household discrimination, number of primary caregiver losses,
and time since loss. Together these explain a fifth of the grief
found two or more years after parental death (R2adj 0.21). Other
theoretical predictors of complicated grief including age, sex, sudden
or violent death, living with the deceased parent or experiencing
their prolonged illness prior to death were not associated.
Expected comorbidities with depression, suicidal thoughts, PTSD,
and functional impairment in everyday tasks were confirmed,
underscoring construct validity.
Conclusion: One-third of orphans exhibit debilitating grief two or
more years after parent death. While these data highlight the
centrality of community-based initiatives that sensitise caregivers of
orphans to alleviate stigma and discrimination, additional research on
children with complicated grief suggests benefits from more focussed
interventions. Screening tools and effective counselling interventions
adapted for this rural African population are urgently needed.
Track D Social Science, Human Rights and Political Science
HIV prevalence vs GINI scatterplot.
Predictor
95% CI,
95% CI,
Coefficient
p value
lower
upper
0.088
0.001
0.039
1.38
0.029
0.010
0.050
0.001
0.032
0.372
0.104
0.040
GINI
coefficient
(/10)
Total income,
USD (*10)
Urban
(vs. rural)
Regression HIV prevalence GINI.
WEPDD0304
Community-level income inequality and HIV prevalence in
injecting drug users in Thai Nguyen, Viet Nam
T. Lim1, V. Go1, T.V. Ha2, N.L. Minh3, C. Viet Anh2, W. Davis4 and
V.M. Quan2
1
Johns Hopkins Bloomberg School of Public Health, International
Health, Baltimore, United States. 2Johns Hopkins Bloomberg School
of Public Health, Department of Epidemiology, Hanoi, Viet Nam.
3
Center for Preventive Medicine, Thai Nguyen, Viet Nam. 4Johns
Hopkins Bloomberg School of Public Health, Department of
Epidemiology, Baltimore, United States
Presenting author email: travis.lim@mail.mcgill.ca
Background: There is mixed evidence on the association between
HIV prevalence and poverty, but an increasing number of studies
have found a positive association between HIV prevalence and
income inequality, especially among countries with generalized
epidemics. Less is known about the association between income
inequality and HIV prevalence in concentrated epidemics, such as
among injection drug users in Vietnam, or whether this association
holds at the community level.
Methods: 1674 male IDUs, and 1349 community members (40%
male) living in physical proximity, were recruited throughout Thai
Nguyen. Both IDUs and community members completed crosssectional surveys. IDUs were tested for HIV. The GINI coefficient for
income inequality was calculated for each commune from the selfreported incomes of non-IDU community members. Scatterplots of
the communes were then constructed to compare community-level
income inequality and HIV prevalence among IDU.
Results: The HIV prevalence among IDU in 32 communes in Thai
Nguyen is 31.2% (4.3%63.6%). There is a statistically significant
positive correlation of 0.59 (pB0.001) between HIV prevalence
among IDU and the income inequality level of communes, weighted
by population.
A regression of HIV prevalence as a function of GINI coefficient
shows that an increase in GINI coefficient of 0.10 is independently
associated with an 8.8% increase in HIV prevalence (p 0.001),
controlled for mean income of the commune.
Conclusion: To our knowledge, this is the first analysis demonstrating
the association between income inequality and HIV prevalence at a
community level, where social and cultural factors are relatively
homogenous. It is also the first to demonstrate the association
between income inequality among the general population and the
HIV prevalence of a high risk group in a concentrated epidemic.
The results suggest that the distribution of local economic resources
is related to HIV infection in high risk groups.
WEPDD0305
Does the ‘inverse equity hypothesis’ explain how both
poverty and wealth can be associated with HIV
prevalence in sub-Saharan Africa?
J. Hargreaves1,2, C. Davey1 and R. White1
1
London School of Hygiene and Tropical Medicine, Department of
Infectious Disease Epidemiology, London, United Kingdom. 2Chatham
House Centre on Global Health Security, London, United Kingdom
Presenting author email: james.hargreaves@lshtm.ac.uk
175
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Background: A controversial aspect of HIV/AIDS epidemiology has
been whether it is relative wealth or relative poverty that is a key driver
of the epidemic in sub-Saharan Africa. We hypothesised that the social
epidemiology of HIV in Africa is changing from a situation where more
new infections are acquired by those of relatively high socioeconomic
position (SEP), to one where those of relatively low SEP are at greater
risk. We suggested this pattern is compatible with the inverse equity
hypothesis from child heath that suggests those of higher socioeconomic position benefit first from new health interventions.
Methods: We analysed Demographic and Health Survey (DHS) data
from sub-Saharan African countries with two surveys measuring HIV
prevalence or with a second expected in the next two years. We
inspected the pattern of HIV prevalence by SEP, indicated by education
status. In the countries with two surveys we calculated the percentage
risk difference for HIV prevalence stratified by education and sex.
Results: Data were available for eleven countries: four with two
surveys and seven expecting a second survey within two years. In the
first/only survey, higher SEP is broadly associated with higher HIV
prevalence. In countries with two surveys, HIV prevalence has risen
in the no education group in all cases except among women from
Lesotho, and fallen among those with secondary education in all
cases except women from Malawi.
Conclusion: Available evidence strongly suggests that in the
early phase of the epidemic HIV infections were concentrated
among those of higher SEP. Our analysis supports the inverse
equity hypothesis that new infections will increasingly concentrate
in people of lower SEP because of lower access to public health
interventions. Data that will be available within the next two years
will further test this hypothesis. The inverse equity hypothesis has
important implications for policy and resource allocation.
WEPDD0306
‘There is hunger in my community’: food security as a
cyclically driving force in sex work in Swaziland
R. Fielding-Miller1, Z. Mnisi2, N. Dlamini3, S. Baral4 and C. Kennedy4
1
Emory University Rollins School of Public Health, Behavioral
Sciences and Health Education, Atlanta, United States. 2Swaziland
Ministry of Health and Social Welfare, SNAP, Mbabane, Swaziland.
3
Swaziland Ministry of Health and Social Welfare, Mbabane,
Swaziland. 4Johns Hopkins Bloomberg School of Public Health,
Baltimore, United States
Presenting author email: rfieldi@emory.edu
Background: Swaziland has the highest HIV prevalence in the world.
Many Swazis are chronically food insecure. Globally and within
southern Africa, food insecurity has been linked to high-risk sexual
behaviors, difficulty with antiretroviral (ARV) adherence, higher rates
of mother-to-child transmission, and more rapid HIV progression.
Methods: In-depth interviews were conducted with 20 HIV female
sex workers (SWs) in Swaziland. Interviews took place in four
different regions of the country, and were designed to learn about
context, experiences, and health service needs amongst Swazi sex
workers. Interviews were coded in Atlas.ti.
Results: Hunger was a consistent, major theme in our informants’
lives. Women cited their own hunger or that of their children as the
impetus to begin sex work, and as a primary force in continuing
to sell sex. Nearly all informants requested food-related services
(parcels, grants, or education) when asked about desired programming. Good nutrition and the ability to eat ‘‘healthy’’ or ’’balanced‘‘
foods was seen as an important means of controlling HIV disease
progression. Informants discussed difficulty in adhering to ARVs
when faced with taking pills on an empty stomach. Across interviews,
Track D Social Science, Human Rights and Political Science
discussions of CD4 counts and ARV adherence intertwined with
discussions of poverty, hunger and healthy foods. Food security and
food sharing were also seen as important expressions of social
networks, which many SWs felt they had trouble accessing as a result
of both their HIV status and profession.
Conclusion: Informants described a risk cycle of hunger driving sex
work driving HIV infection. The two latter in turn drive an increased
need for ‘healthy foods’ and an alienation from social networks
which offer material and emotional support against hunger. Poverty
and food security are concrete, vital issues in the lives of SWs
living with HIV in Swaziland, issues that cannot be ignored when
conceptualizing risk or designing services.
D13 - Migration, social movements and
population dislocation: mobile and
immigrant populations (including
people living with HIV)
THPDD0104
Increasing HIV testing among African refugees in Africa:
intervening in the daily survival cycle to encourage
priority shifting
K.N. O’Laughlin1,2, Z.M. Faustin3, S.A. Rouhani1,2,4 and N.C. Ware2,5
1
Brigham & Women’s Hospital, Emergency Medicine, Boston, United
States. 2Harvard Medical School, Boston, United States. 3Bugema
University, Kampala, Uganda. 4Massachusetts General Hospital,
Boston, United States. 5Brigham & Women’s Hospital, Boston,
United States
Presenting author email: kolaughlin@partners.org
Background: Despite recent efforts to increase HIV testing in subSaharan Africa, poor testing availability and limited uptake in refugee
populations persists. Refugees require additional focused efforts
because many have suffered human rights violations putting them
at increased HIV- risk. Our objective was to qualitatively study
refugees’ utilization of services in a refugee settlement where HIV/
AIDS services are available.
Methods: Open-ended interviews were conducted with HIV-infected
refugees living in Nakivale Refugee Settlement in southwest Uganda.
Interviews focused on: (1) accessibility of HIV/AIDS-related testing
and care; (2) experiences of ART adherence; and (3) perspectives on
how to improve access to testing and care, adherence, and retention.
Data were collected at the Nakivale HIV/AIDS Clinic from March
to July of 2011 and included patient (N 73) and staff (N 4)
interviews, and observations of clinical activities. For this analysis,
category construction methods were used to analyze the data
relating to HIV testing.
Results: Refugees, because of competing daily hardships, do not
prioritize HIV testing. Refugees living with HIV/AIDS often present to
clinic for testing and initial evaluation with very advanced disease.
Reported barriers to HIV testing for Nakivale refugees reflected in the
data include: difficulty physically accessing testing facilities; fear
of stigma associated with HIV diagnosis; low self-perceived risk of
disease, and lack of knowledge regarding the potential benefits of
medical therapy. Given the competing priorities for survival, HIV tests
are not obtained until special circumstances lead to temporary
priority shifting.
Conclusion: Understanding how HIV testing fits among the survival
priorities of refugees will help in designing effective interventions.
To increase HIV testing for refugees, efforts should aim to intervene
176
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
in the survival cycle to encourage priority-shifting. Intervention
approaches may include improving accessibility, providing incentives
and increasing HIV-related education.
D14 - Family structures, kinship, and
social safety nets for widows, orphans
and other vulnerable groups
MOAD0305
The psychosocial impact of HIV on the siblings of infected
children
T. Marukutira1,2, G. Letamo3, V. Mabikwa1,2, G. Karugaba1,2,
J. Makhanda1,2, M. Marape1,2,4, R. Seleke1,2 and G.M. Anabwani1,2,4
1
Botswana-Baylor Children’s Clinical Center of Excellence, Gaborone,
Botswana. 2Baylor International Pediatric AIDS Initiative, Baylor
College of Medicine, Pediatric Retrovirology, Houston, United States.
3
University of Botswana, Gaborone, Botswana. 4Texas Children’s
Hospital, Pediatrics, Houston, United States
Presenting author email: ganabwani@baylorbotswana.org.bw
Background: There is paucity of published data on ways in which HIV
in children receiving Highly Active Antiretroviral Therapy (HAART)
impacts other children living within the same households. We
investigated the psychosocial impact of HIV on the siblings of HIV
infected children.
Methods: Data were collected using pre-tested interviewer administered questionnaires and focus group discussions. Twelve 12 HIV
treatment sites which account for over 90% of children receiving
HAART in Botswana participated. HIV affected children were defined
as those aged 6-18 years who were living in the same household as
documented HIV-infected children. Ethical approval was obtained
from the Botswana Ministry of Health and Baylor College of Medicine.
Results: Of the 258 HIV affected children, 251 (97.3%) were
attending school; 206 (79.8%) and 52 (20.2%) had been fully or
partially disclosed to respectively. 153 (59.3%) were siblings of the
HIV-infected children, 79 (30.6%) were cousins and 26 (10%) were
related in other ways. 223 (86.4%) had lived together with the HIVinfected children for longer than 5 years. 11 (4.3%) said that living
with an HIV-infected child made them feel different because of
stigma, playing caregiver roles, fear of contracting HIV, and feeling
sad. 65 (25.4%) faced various problems, including: worrying about
the HIV infected child; receiving less attention from caregivers; and
experiencing stress due to adherence-related issues, stigma, and
family disharmony. They coped by crying, talking to an adult relative,
talking to the HIV-infected child or isolating themselves from others.
230 (89%) felt sad or scared/anxious whenever the HIV-infected child
was sick. 254 (98.4%) reported playing caregiver roles, such as
reminding or giving medications to the infected children.
Conclusion: Although HIV affected children are not the prime targets of paediatric HIV interventions, they face many psychosocial
challenges. Programs and policies aimed at ameliorating the impact of
HIV should take these findings into account.
WEPDD0104
Care and support by households and extended families in
the era of HIV treatment: responses to HIV and AIDS in
rural South Africa
L. Knight1, V. Hosegood2,3 and I. Timaeus4
Track D Social Science, Human Rights and Political Science
1
Human Sciences Research Council, HIV/AIDS, STIs and TB Unit,
Durban, South Africa. 2University of Southampton, Social Sciences:
Social Statistics & Demography, Southampton, United Kingdom.
3
Africa Centre for Health and Population Studies, Mtubatuba
South Africa. 4London School of Hygiene and Tropical Medicine,
Department of Population Studies, London,
United Kingdom
Presenting author email: lknight@hsrc.ac.za
Background: The last century’s economic and political upheavals are
widely believed to have reduced African and particularly South
African families’ cohesion and ability to function collectively. AIDS
has compounded this threat to the resilience of households and
wider family networks. We explore the resilience of families to AIDS
and demonstrate that theories of social capital, family obligation and
reciprocity can help to explain access to familial support in rural
KwaZulu-Natal, South Africa.
Methods: Data were collected over a 7-month period from a small
sample of households dealing with AIDS illness or death using indepth interviews and participant observation. Retrospective and
prospective data about households’ experiences were analysed using
framework analysis and the development of household case studies
for comparisons.
Results: Affected households and individuals drew on family
relationships for financial and material support and physical care.
Close family members, often sharing a common sense of home and
family, were the most important source of care and support.
Their greatest motivation was a strong moral obligation to family,
associated with norms of familial assistance. Support from other
family varied depending on whether levels of mutual trust, investment in social capital and physical proximity, enabled negotiated
reciprocal exchange. Families suffering from conflicting obligations,
conflict, severe poverty or extreme illness were more likely to be
excluded from these networks and suffered because of their inability
to secure familial support.
Conclusion: Despite examples of exclusion, we demonstrate that
social capital, reciprocity and a sense of family obligation persist in
families responding to the impacts of AIDS, contributing to them
maintaining cohesion, collective functioning and ultimately ensuring
their resilience. Interventions to support the treatment, care and wellbeing of sick individuals need the flexibility to be able to both support
families in their efforts to provide these services and address the
needs of people without access to supportive family networks.
WEPDD0105
Family network proportion and HIV risk among black men
who have sex with men
J.A. Schneider1,2, S. Michaels3 and A. Bouris4
1
University of Chicago, Medicine, Chicago, United States. 2University
of Chicago, Health Studies, Chicago, United States. 3National Opinion
Research Center, Chicago, United States. 4University of Chicago,
Social Services Administration, Chicago, United States
Background: Black men who have sex with men (BMSM) have
the highest rates of HIV in the United States. Despite increased
attention to social and sexual networks as a framework for
biomedical intervention, the role of family in these networks and
their relationship to HIV prevention has received limited attention.
Methods: A network sample of BMSM and their family members
(N 380) was generated through respondent driven sampling of
BMSM and elicitation of their personal networks. The proportion of
personal networks that were family was calculated and weighted
logistic regression was used to assess the relationship between this
177
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track D Social Science, Human Rights and Political Science
Discourages
Network
Proportion*
N(%)
Discourages
UAI
Sex-drug use
Group Sex
Discourages UAI
sex-drug use
group sex
AOR (95% CI)
AOR (95% CI)
AOR (95% CI)
AOR (95% CI)
AOR (95% CI)
AOR (95% CI)
Family Network (%)
0%
2039%
111 (54.7) ref
40 (19.7) 1.48 (0.673.27)
ref
ref
0.51 (0.241.05)$ 0.51 (0.141.84)
40%
52 (25.6)
0.38 (0.170.87)% 0.25 (0.100.67)§ 1.66 (0.554.99) 2.18 (1.353.54)§ 3.83 (1.569.43)§
0.68 (0.341.36)
ref
ref
1.05 (0.343.20) 0.89 (0.421.90)
ref
2.12 (0.885.11)$
Male Family Network
0%
150 (73.9) ref
ref
ref
ref
2039%
33 (16.3)
1.26 (0.523.03)
0.55 (0.251.22)
0.53 (0.142.02)
1.07 (0.343.39) 1.37 (0.742.55)
ref
40%
20 (9.9)
0.37 (0.111.21)$ 0.26 (0.061.22)$ I
ref
1.33 (0.573.09)
1.54 (0.396.10) 2.98 (1.177.61)% 3.37 (0.9511.9)$
Black men who have sex with men (BMSM) family netw.
*Proportion of close network members who are family. This is further limited to male family network proportion.
Models are weighted and control for age, education, employment status, HIV status, network size and site of participant recruitment.
$p B0.1.
%p B0.05.
§p B0.01.
Imodel doesn’t converge.
proportion and unprotected anal intercourse (UAI), sex-drug use
(SDU) and group sex (GS); as well as intravention efforts to
discourage these risk behaviors among their MSM social networks.
Results: 45.3% of respondents listed at least one family member in
their close personal network. Greater family network proportion
(having 2 or more family members in the close network) was
associated with less SDU [adjusted odds ratio (AOR 0.38(0.170.87))]
and participation in GS (AOR 0.25(0.100.67)). For intravention,
BMSM with greater family proportion were more likely to discourage
GS (AOR 3.83(1.569.43)) and SDU (AOR 2.18(1.353.54)) among
their MSM friend network. Moreover, increased male family network
proportion was associated with lower HIV-risk and greater intravention than increased female network proportion.
Conclusion: Nearly half of BMSM have a close family member with
whom they share personal information. Male family networks have
received little attention previously. Combination prevention interventions might be made more potent if family networks, an often
overlooked component of personal networks, were incorporated.
D15 - Violence and conflict: political,
gender, social, structural, interpersonal
and family-based
WEAD0103
through targeted approaches that address gender disparities and
power imbalances. The baseline survey, part of the ZPI evaluation
plan, identifies key areas for targeting.
Methods: A total of 1,060 men (aged 1559) and 1,700 women
(aged 1549) participated in a survey conducted in 4 provinces.
Provinces and districts were purposively selected; households
and individuals were randomly selected. The survey included
questions related to gender-based violence, rape myths that
blame women for rape (i.e., If a woman doesn’t physically fight
back, you can’t really say it was rape), and attitudes towards gender
norms (measured using the Gender Equitable Men scale) and
contraception.
Results: 68% of females ever experienced either or both physical
(35%) or sexual abuse (39%); only 15% sought help. 62% of all
respondents endorsed at least 1 of 4 rape myths and 37% supported
inequitable gender norms. Those with 2 partners (46%) in the last
12 months were more likely to support inequitable norms than those
with 1 partner (39%) or no partners (26%) (p B 0.001). Nearly 20%
of men think that contraception is women’s business; 32% think
women who use contraception are promiscuous. When women were
asked about their last birth, 50% indicated they wanted to wait or did
not want the pregnancy at all. Unintended pregnancies were highest
among unmarried younger females (7785%) compared to married
women aged 25 (50%).
Conclusion: Inequitable gender norms are pervasive and may affect
women’s vulnerability to HIV and gender-based violence. ZPI is addressing power imbalances between men and women that contribute to HIV risk and focusing on male norms and behaviors that
contribute to gender-based violence.
Gender disparities and inequitable gender norms:
implications for HIV prevention programming in Zambia
W. Tun1, J. Keesbury2, F.N. Simmonds3, M. Sheehy4, T. Moyo3,
C. Rathner5 and S. Kalibala1
1
Population Council, HIV and AIDS Program, Washington, United
States. 2PATH, Washington, United States. 3Population Council,
Zambia, Lusaka, Zambia. 4Population Council, HIV and AIDS Program,
New York, United States. 5FHI 360 Zambia, Lusaka, Zambia
Presenting author email: wtun@popcouncil.org
Background: In Zambia, HIV prevalence in women (1524) is twice
that of same aged men. A gender perspective is critical for designing
interventions that recognize gendered-risks to HIV. The Zambia-led
Prevention Initiative (ZPI) is initiating community-level interventions
WEAD0104
Abuse and mortality in women with and at risk for HIV
K. Weber1, S. Cole2, D. Agniel1, R. Schwartz3, K. Anastos4, J. BurkeMiller1, M. Young5, E. Golub6 and M. Cohen1,7
1
Cook County Health & Hospital Systems, The CORE Center, Chicago,
United States. 2University of North Carolina-Chapel Hill,
Epidemiology, Chapel Hill, United States. 3SUNY Downstate Medical
Center, Preventative Medicine and Community Health, Brooklyn,
United States. 4Montefiore Medical Center & Albert Einstein College
of Medicine, Department of Medicine, Bronx, United States.
178
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track D Social Science, Human Rights and Political Science
5
Georgetown University Medical Center, Department of Medicine,
Washington, United States. 6Johns Hopkins School of Public Health,
Baltimore, United States. 7Rush University Medical Center,
Department of Medicine, Chicago, United States
Presenting author email: weberkathleen@ameritech.net
Background: Gender based violence (GBV) is a human rights violation and public health problem impacting women’s health globally
and is interconnected with the HIV epidemic. GBV is associated with
reduced adherence, poor treatment outcomes, and mortality in
women with HIV.
Methods: Using marginal structural survival models (MSMs) we
evaluated the effect of sexual, physical, or emotional abuse in the
past 12 months on mortality among 2,222 (1,642 HIV-infected and
580 seronegative) participants in the Women’s Interagency HIV Study
(WIHS), an ongoing cohort study. Mortality data were confirmed
by National Death Index Plus registry match. MSMs were used to
estimate the mortality hazard ratio and survival curves from baseline
(1994/95 or 2001/02) through 2007, controlling for sociodemographic, behavioral, and clinical factors.
Results: Overall, 437 (19.7%) women died between 1994 and 2007 and
had abuse data available in the year prior to death. Compared to
survivors, women who died were more likely to be older, HIV-infected
and not treated with highly active antiretroviral therapy; have lower
nadir and current CD4; to have engaged in transactional sex and used
drugs and tobacco; be depressed, report lower cognitive function, and
have a history of pre-study abuse including childhood sexual abuse.
Accounting for these fixed and time-varying confounders, recent abuse
was independently associated with all cause mortality (HR 1.54; CI
1.18, 2.02); findings remained significant in analyses stratified by prebaseline abuse history, and by HIV serostatus. This effect was greater in
uninfected (HR 4.39; CI 1.78, 10.82) than HIV infected women (HR 1.42;
CI 1.07, 1.89).
Conclusion: Mortality risk is significantly elevated for women
exposed to GBV and appreciable even in the context of a high death
rate due to HIV infection. Interventions to address GBV should
remain a public health priority. Further research is needed to identify
possible biologic pathways underlying abuse related sequelae.
Male SV Victims Non-Victims
2 casual partners in
P-Value
55.9%
40.6%
Always use condoms
29.2%
38.8%
0.03
Transactional sex with
a woman ever
80.3%
62.0%
B.0001
Sex with a female sex
29.7%
18.7%
B.0001
Weekly binge drinking
20.1%
12.1%
0.01
Perpetration of
58.8%
40.9%
B.0001
51.3%
25.4%
B.0001
5.8%
2.7%
63.8%
41.5%
B.0001
the past year
worker ever
physical violence
against a female
intimate partner
Perpetration of sexual
violence against a
female intimate
partner
Perpetration of sexual
0.02
violence against
another man
Self-report STI
Symptoms
B.0001
Risky behavior: Male victims of sexual violence.
2 casual partners in the
Male SV
Perp
Non-Perp
P-Value
68.9%
41.0%
B.0001
past year
Always use condoms
28.6%
38.3%
0.05
Transactional sex with a woman
88.0%
63.8%
B.0001
B.0001
WEAD0106
Sex with a female sex worker
43.5%
19.0%
HIV risk behaviour among victims and perpetrators of
male-on-male sexual violence in South Africa: results
from a population-based survey
Weekly binge drinking
18.4%
12.6%
0.19
Perpetration of physical
82.2%
41.2%
B.0001
K. Dunkle1, R. Jewkes2, D. Murdock1, Y. Sikweyiya2 and R. Morrell3
1
Emory University, Behavioral Sciences and Health Education,
Atlanta, United States. 2Medical Research Council of South Africa,
Gender and Health Research Unit, Pretoria, South Africa. 3University
of Cape Town, Programme for the Enhancement of Research
Capacity, Cape Town, South Africa
Presenting author email: kdunkle@emory.edu
intimate partner
88.0%
25.7%
B.0001
65.3%
42.8%
0.005
Background: Links between experience of sexual violence and HIV
risk behavior among women are well established, as is the fact that
male perpetrators of sexual violence against women report high
levels of risk behavior. Links between sexual violence victimization
and HIV risk have also been reported for MSM. However, little data
has explored links between male-on-male sexual violence and HIV
risk among men in the general population, and almost no such data
exists from developing countries.
Methods: We conducted a population-based household survey of
1,738 men aged 1845 across two provinces in South Africa.
Information on sexual behavior, and experience and perpetration
of male-on-male sexual violence was collected using audio-enhanced
personal digital assistants.
violence against a female
Perpetration of sexual violence
against a female intimate
partner
Self-report STI Symptoms
Results: 9.6% (95% CI: 8.211.3) of men in the general population
reported any sexual violence victimization by another man; 3.4%
(95% CI: 2.74.3) reported anal/oral rape. 3.0% (95% CI: 2.24.0) of
men reported perpetrating any male-on-male sexual violence; 1.9%
(95% CI: 1.32.7) reported anal/oral raping. Men who reported any
sexual victimization reported more sexual partners, lower condom
use, increased participation in economically motivated sex with
women, increased alcohol consumption, and increased perpetration
of violence against both female intimate partners and against other
men, and more STI symptoms.
Similar increased risks were reported by men who perpetrated
male on male sexual violence, with the exception of alcohol use.
179
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Conclusion: Male-on-male sexual violence victimization and perpetration are common among men in the general population in
South Africa and are associated with increased HIV risk behavior,
as well as increased violence against women. Efforts to address the
links between violence and HIV in South Africa must be extended
to include prevention of male-on-male sexual violence, comprehensive support for male survivors of such violence, and efforts to
address male-on-male perpetration.
MOPDD0205
Alarming rates of occupational violence and associated HIV
risks among young female sex workers in post-conflict
northern Uganda
K. Muldoon1,2, M. Akello3, G. Muzaaya3, A. Simo1 and K. Shannon1,2
1
BC Centre for Excellence in HIV/AIDS, Vancouver, Canada.
2
University of British Columbia, Vancouver, Canada. 3The AIDS
Support Organization, Gulu, Uganda
Presenting author email: katherine.muldoon@gmail.com
Background: As northern Uganda emerges from decades of war
and displacement, a growing number of young women engage in
sex work (SW) for survival. With the escalating rates of HIV,
the normalization of violence in northern Uganda creates a high
occupational risk environment for young SWs. We aim to investigate
the prevalence of client violence and associations with HIV risks
among a cohort of SWs in Gulu, northern Uganda.
Methods: We conducted an analysis of baseline data (questionnaire
and HIV screening) of SWs enrolled in a prospective cohort. Young
women ( ]14 years) who exchanged sex for resources in the last 30
days were recruited through ethnographic mapping, time-location
sampling and peer outreach (current SWs) to SW venues. Bivariate
and multivariate logistic regression modeled associations with
physical and/or sexual violence by clients among SWs.
Results: Of 400 SWs, the median age was 21 (IQR: 1925). The
majority were Acholi (92.3%) with 66.5% (266) having formerly lived
in displacement camps, 34.0% (136) living with HIV. In the last six
months, 83.7% (335) had experienced violence by clients: 69.0%
(276) forced unsafe sex, 28.8% (115) stabbed, and 18.8% (75) raped.
In multivariate logistic regression, client violence was independently
associated with rushing negotiations with a client due to police
presence (a-OR: 3.58, 95% CI: 1.687.64), inconsistent condom use
by regular and one time clients (a-OR: 3.53, 95% CI: 1.896.86), and
older age (a-OR:1.08, 95% CI: 1.011.17).
Conclusion: The SW risk environment in northern Uganda is
characterized by extreme occupational violence directly associated
with a 3.5-fold increase risk of non-condom use. The criminalization
of sex work in Uganda contributes to 3.5-fold increased odds of client
violence from rushing negotiation due to police presence. Structural
interventions (decriminalization and enforcement-based approaches)
must be integrated into the HIV response, both as a human rights
and public health imperative.
D16 - HIV-related stigma, layered
stigmas and marginalized identities
WEAD0501
Success! Interventions that work to reduce HIV stigma and
discrimination in communities: results of an evaluation
study in Thailand
A. Jain1, R. Nuankaew2, P. Oranop na Ayuthaya3 and K. Richter4
Track D Social Science, Human Rights and Political Science
1
Johns Hopkins University, Baltimore, United States. 2Population
and Community Development Association, Bangkok,
Thailand. 3PACT Thailand, Bangkok, Thailand. 4Mahidol
University, Institute for Population and Social Research
Nakhon Pathom, Thailand
Presenting author email: aparna727@gmail.com
Background: The Population and Community Development Association implemented the Positive Partnership Program (PPP), which
pairs HIV positive and HIV negative individuals and provided pairs
loans for income generating businesses. Pairs also collaborated to
disseminate HIV/AIDS knowledge to their community, with the
objective of reducing community-level stigma and discrimination.
Interventions included monthly HIV campaign events, funfairs, and
production of three IEC materials (radio dramas, posters, and slips of
paper with HIV messaging).
Characteristics
Baseline (N560)
Endline (N 560)
58.6
41.4
58.8
41.3
22.5
17.9
23.0
37.1
20.0
19.5
23.2
37.3
GENDER
- Female
- Male
AGE
- 15 29
- 30 39
- 40 49
- 50
Community Respondent Profile, Baseline and Endline.
The study goal is to evaluate the effect of interventions on
reducing community-level stigma.
Methods: Randomly selected households and individuals were
interviewed at baseline (N 560) and endline (N 560). We
conducted t-tests on three stigma domains: fear of HIV infection
through daily activity; shame associated with having HIV; and blame
towards people with HIV. We developed three scales using
confirmatory factor analysis and regressed each stigma scale on
demographic characteristics, HIV knowledge, and exposure to
intervention activities.
CHARACTERISTICS
- Female (refmale)
- Personally know a PLHIV
(ref does not know)
- 4 9 correct HIV
knowledge responses
(ref 0 3 correct
responses)
B Coefficient
(95% Confidence
Interval)
1.37
2.42
(0.36: 3.10)
(4.34: 0.51)
4.71
(6.35: 3.07)
ref
0.98
2.86
(2.95: 0.98)
(6.82: 1.10)
4.18
1.70
(7.74: 0.63)
(6.44: 3.04)
INTERVENTION EXPOSURES
- None or one
- Two
- Campaign/VDB or PPP
club/IEC
- Campaign/Funfair/IEC
- Four
Results of Linear Regression on Fear-Driven Stigma.
Results: No differences were observed in respondent characteristics
at baseline and endline.
Significant changes were observed in HIV transmission knowledge
and fear of HIV infection from baseline to endline.
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track D Social Science, Human Rights and Political Science
Figure 1. Change of HIV Knowledge Among Community Members.
Figure 2. Change in Fear of HIV Transmission Among Community Members.
181
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Respondents exposed to the monthly campaign, funfair and
IEC materials were less likely to exhibit stigma along the dimensions
of fear (4.2 points lower on average compared to respondents
exposed to none or only one intervention; 95% CI: 7.4 to 0.6)
and shame (4.7 points lower; 95% CI: 8.4 to 1.1), net of
demographic controls and baseline levels of stigma. Personally
knowing someone with HIV is associated with low fear and shame,
and females are less likely to possess attitudes of shame compared
to males.
CHARACTERISTICS
- Female (refmale)
- Personally know a PLHIV
(ref does not know)
- 4 to 9 correct HIV
knowledge responses
(ref 0 3 correct
responses)
B Coefficient
(95% Confidence
Interval)
2.17
1.78
(3.92: 0.41)
(3.72: 0.15)
3.73
(5.40: 2.06)
ref
0.88
0.60
(2.98: 1.14)
(7.84: 9.04)
INTERVENTION EXPOSURES
- None or one
- Two
- Funfair/Campaign/ VDB or
PPP club
- Campaign/VDB or PPP/ IEC
- Funfair/Campaign/IEC
- Four
1.11
4.73
5.76
(5.13: 2.90)
(8.35: 1.11)
(10.59:
0.94)
Results of Linear Regression on Shame Stigma.
Conclusion: Results suggest that a combination of three interventions is critical in shifting community-level stigma in Thailand:
monthly campaigns, funfairs, and exposure to IEC materials. Knowing
which interventions to invest in for maximum impact is crucial for
country-wide expansion and scale-up of interventions.
WEAD0503
Stigma and serostatus disclosure within partnerships in four
African countries: a mixed methods approach
A. Hardon1, G. Bongololo-Mbera2, P. Cherutich3, G.B. Gomez4,
E. Kahega1, O. Ky-Zerbo5, E. Vernooij1, R. Wanyenze6 and
C. Obermeyer7
1
Amsterdam Institute for Social Science Research, Amsterdam,
Netherlands. 2Research for Equity and Community Health Trust,
Lilongwe, Malawi. 3National AIDS/STD Control Programme, Ministry
of Health, Nairobi, Kenya. 4Amsterdam Institute for Global Health
and Development, Amsterdam, Netherlands. 5Programme d’Appui au
Monde Associatif & Communautaire de Lutte Contre le VIH/SIDA,
Ouagadougou, Burkina Faso. 6Makerere University School of Public
Health, Kampala, Uganda. 7American University of Beirut, Faculty of
Health Sciences, Beirut, Lebanon
Presenting author email: g.gomez@aighd.org
Background: Disclosure of seropositivity within a partnership is a
pre-requisite for couples counseling and the tailoring of prevention
interventions, such as the use of treatment as prevention. In this
study, we used a mixed methods approach to describe the rates and
determinants of disclosure within partnerships.
Methods: The Multi-Country African Testing and Counseling for HIV
study was a cross-sectional study designed to compare clients’
Track D Social Science, Human Rights and Political Science
experiences of HIV testing services in Burkina Faso, Kenya, Malawi,
and Uganda. Face-to-face questionnaires were administered and
included multiple-choice and open-ended questions. Our analysis
focuses on a sub-set of married/cohabiting participants reporting
awareness of their seropositive status. We explore the influence of
stigma through a multilevel logistic regression model.
Results: Of the 477 participants, 85.3% [95%CI 82.188.5] reported
ever disclosing their serostatus. However, only 52.6% [95%CI 48.1
57.1] reported disclosing to their partners. We observed a significant
variation between countries-participants in Kenya and Burkina Faso
disclose at similar levels, while lower levels of disclosure were
reported in Malawi and Uganda. Analysis of the open-ended
responses among HIV positives who did divorce, revealed that
disclosure can create serious rifts with partners. Perceived community
stigma was approximately reported at same levels across the
four countries, but levels of self-stigma differed. Patients were more
likely to report self-stigma in Burkina Faso, while they were the least
likely to report self-stigma in Malawi. However, none of our stigma
indicators was associated with disclosure. At individual level, those
with a lower education and member of a support group disclose less
than the rest.
Conclusion: Seropositive patients tend to disclose to people in their
support network. However, disclosure within the partnership is less
common. We found no relationship between stigma and disclosure
to partners. A tailored disclosure support and advice will be essential
for programs looking at implementing treatment as prevention in
serodiscordant couples.
WEAD0504
Internal stigma among HIV-positive adults in Ethiopia
T. Bezabih
World Food Programme, Programme/Nutrition and Education/HIV
and AIDS, Addis Ababa, Ethiopia
Presenting author email: tsegazeab.bezabih@gmail.com
Background: Internal stigma or self-stigmatization is a critical problem
among PLHIV as it usually leads to low self-esteem, a sense of
worthlessness and depression, etc. The objective of this study is to assess the level of internal stigma among HIV-positive adults in Ethiopia
Methods: This study utilized a nationally representative two-stage
cluster sampling method to collect data from 3360 PLHIV (68% of
them women) sample cases.
Results: More than half of the PLHIV blamed themselves and
reported to have low self-esteem. More than 40 percent of the
PLHIV feel ashamed and guilty because of their HIV status. PLHIV
residing in rural areas have higher likelihood of feeling guilty
than PLHIV residing in urban areas. One out of five of the PLHIV
felt suicidal, in connection with their HIV positive status. Abandoning
aspirations/life goals, in connection to their HIV-positive status
was reported by substantial proportion of PLHIV. For instance, the
proportion of PLHIV who took the decision not to have (any more)
children was 59 percent,), not to have sex was 40 percent and not to
get married 37 percent. Significantly higher proportion of female
PLHIV were noted to have taken all these decisions compared to
males (P 0.000). Almost one-quarter of PLHIV revealed that they
have isolated themselves from their family and/or friends as a result
of their being HIV-positive. Nearly equal proportion of PLHIV have
decided to withdraw from their education/training and stopped
working (12 percent) because of their HIV-status.
Conclusion: Internal stigma and its negative consequences are very
common among PLHIV in Ethiopia. This may deter PLHIV from active
participation in socio-economic activities of the community out of a
fear of having their status revealed or being discriminated against. In
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
order to address the problem, peer-to-peer support groups, skills
building, network building, counselling, training, should be given
attention.
WEPDD0103
Risk and protective factors for depression symptoms among
children affected by HIV/AIDS in rural China: a structural
equation modeling analysis
B. Wang, X. Li, B. Stanton and P. Chi
Wayne State University, Detroit, United States
Presenting author email: pch@med.wayne.edu
Background: Previous research has revealed a negative impact of
orphanhood and HIV-related stigma on the psychological wellbeing of children affected by HIV/AIDS. Little is known about
psychological protective factors that can mitigate the effect of
orphanhood and HIV-related stigma on psychological well-being. This
research examines the relationships among several risk and protective factors for depression symptoms using structural equation
modeling.
Methods: Cross-sectional data were collected from 755 AIDS orphans
and 466 children of HIV-positive parents aged 618 years in 2006
2007 in rural central China. Participants reported their experiences
of traumatic events, perceived HIV-related stigma, perceived social
support, future orientation, trusting relationships with current
caregivers, and depression symptoms.
Results: We found that the experience of traumatic events and
HIV-related stigma had a direct contributory effect on depression
among children affected by HIV/AIDS. Trusting relationships together
with future orientation and perceived social support mediated the
effects of traumatic events and HIV-related stigma on depression.
The final model demonstrated a dynamic interplay among future
orientation, perceived social support and trusting relationships.
Trusting relationships was the most proximate protective factor for
depression. Perceived social support and future orientation were
positively related to trusting relationships.
Conclusion: We conclude that perceived social support, trusting
relationships, and future orientation offer multiple levels of protection that can mitigate the effect of traumatic events and HIV-related
stigma on depression. Trusting relationships with caregivers provides
the most immediate source of psychological support. Future
prevention interventions seeking to improve psychological wellbeing among children affected by HIV/AIDS should attend to these
factors.
D17 - Racism and other forms of social
exclusion
WEAD0502
Racism, sexism, HIV-related stigma and quality of life
among HIV-positive black African Caribbean women in
Ontario, Canada
C. Logie1,2, L. James3, W. Tharao3 and M. Loutfy2
1
University of Calgary, Faculty of Social Work, Calgary, Canada.
2
University of Toronto, Women’s College Research Institute, Toronto,
Canada. 3Women’s Health in Women’s Hands Community Health
Centre, Toronto, Canada
Presenting author email: logiech@yahoo.com
Track D Social Science, Human Rights and Political Science
Background: The deleterious impacts of racism, sexism and HIVrelated stigma on well-being are widely documented, yet most
research has examined these forms of stigma separately. Rising HIV
infection rates among Black African Caribbean women in Canada
underscore the importance of understanding factors associated with
quality of life (QOL). We used a feminist intersectional approach to
examine the influence of racism, sexism and HIV-related stigma on
QOL among HIV-positive Black African Caribbean women in Ontario,
Canada.
Methods: We conducted a community-based multi-method study
triangulating qualitative and quantitative methods. Building on
qualitative findings regarding stigma from 15 focus groups with
HIV-positive women (n 104) in Ontario, we implemented a crosssectional survey with HIV-positive Black African Caribbean women
in three Ontario cities. Multiple linear regression (MLR) analyses
were conducted to measure associations between independent
(block 1: racism, sexism, HIV-related stigma; block 2: resilient coping,
social support) and dependent (total QOL; QOL domains: physical;
psychological; level of independence; social relationships; environment; personal beliefs) variables.
Results: Survey participants (n 163; mean age 40.7 years,
SD 8.8) reported frequent/everyday experiences of racism (29.4%)
and sexism (22.6%) and high HIV-related stigma (disclosure: 84.4%;
personalized: 54.7%; public attitudes 40.4%; negative self-image:
27.6%). In MLR analyses, racism, sexism and HIV-related stigma were
associated with lower QOL scores (total; psychological; level of
independence; social relationships; environment; personal beliefs).
Resilient coping and social support accounted for a significant variance of higher QOL scores (total; psychological; social relationships;
environment) after controlling for the effects of racism, sexism and
HIV-related stigma.
Conclusion: HIV-positive Black African Caribbean women experience
pervasive racism, sexism and HIV-related stigma associated with
reduced QOL; social support and resilient coping were associated
with higher QOL. Interventions tailored for HIV-positive Black
African Caribbean women should aim to strengthen protective factors,
such as resilient coping and social support, and challenge stigma and
discrimination associated with HIV, race/ethnicity and gender.
D21 - Sex and gender
TUAD0301
Condom attitudes of female entertainment workers in
Metro Manila, the Philippines: setting, peer influence and
social support
L.A. Urada1, S.A. Strathdee1, R.F. Schilling2, B. de Guia3 and
D.E. Morisky4
1
University of California at San Diego, School of Medicine/
Department of Medicine, Division of Global Public Health, La Jolla,
United States. 2University of California at Los Angeles, Luskin School
of Public Affairs/Department of Social Welfare, Los Angeles, United
States. 3PAMAC-Q (Peer Educator’s Movement for Empowerment)
and the Philippine Rural Reconstruction Movement, Inc., Quezon
City, Philippines. 4University of California at Los Angeles, School of
Public Health/Department of Community Health Sciences, Los
Angeles, United States
Presenting author email: lurada@ucsd.edu
Background: Female bar/spa workers in the Philippines face continued risk of sexually transmitted infections (STIs), yet Philippine
Congress recently rejected a Reproductive Health Bill. Little is known
about differences in condom attitudes among workers in different
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track D Social Science, Human Rights and Political Science
venues and the effects of social support on their condom attitudes.
This study assesses socio-structural and individual factors associated
with condom attitudes among female bar/spa workers in the Greater
Metro Manila Area, Philippines.
Methods: Female bar/spa workers (N498) from 54 venues
underwent interview-led surveys as part of a larger intervention
study. Multiple hierarchical linear regression analyses, adjusted for
individuals nested within venues, were conducted to assess sociobehavioral (age, education, length of time employed as an entertainer, alcohol, and substance use) and socio-structural (venue type,
manager support, peer support, establishment condom rule, condom
availability at establishment, and social support) factors associated
with condom attitudes.
Results: Participants were aged 1860 years. Over 90% indicated
using condoms every time while having vaginal and anal sex could
lower their chances of contracting HIV/AIDS. However, nearly 70%
considered condoms too expensive to use regularly. Over 60%
said condom usage depended on males in their culture. Over half
thought condoms caused pain or discomfort. A like proportion
indicated that condom usage never or only occasionally went against
their religion. In multivariate analyses, positive attitudes toward
condoms were associated with co-worker peer support (0.35,
pB.01) and working in spa/saunas vs. night club/bars (1.34,
pB.01). Total social support increased the effect of manager support
on condom attitudes (0.02, pB.02). Poorer condom attitudes were
associated with substance use ( 9.66, pB.001).
Conclusion: Socio-structural workplace factors (peer support, social
support, and venue type) over individual factors (excepting substance use) influenced condom attitudes. Attention to sociostructural interventions may be necessary to improve condom
attitudes among female bar and spa workers, especially those
involved in sex work.
18
Rutgers College of Nursing, Nursing, Newark, United States
Presenting author email: knokes@hunter.cuny.edu
Background: In the third decade of the HIV epidemic in the United
States, the population of persons living with HIV/AIDS (PLHIV) has
aged. While 50 and older was initially created as the ‘‘older age’’
category, that cut-point is no longer informative. Understanding the
health status of different adult age-groups of PLHIV will assist in
providing the types of healthcare services needed by an aging
population.
Methods: A convenience sample of 2,182 PLHIV was enrolled
from HIV clinics and service organizations in the United States,
Canada, Puerto Rico, Namibia, China, and Thailand from February
2010 to July, 2011. This subanalysis of U.S. participants (N 1293)
assessed differences in PLHIV in three adult age groups:
4049 (n687, 53%); 5059 (514, 40%); and 60 and older
(n 92, 7%).
Results: Participants’ mean ages were 44.7, 53.4, & 63.9 years; 71%,
73% & 79% male, no differences in race/ethnicity, 64%, 71% & 87%
reported other medical conditions, 81%, 82% & 91% were taking HIV
medications, and 52%, 46% & 40% were diagnosed with AIDS. No
differences were found in social capital (measured by the Social
Capital scale, Onyx & Bullen) or physical functioning (measured by
SF-12); there were significant differences in mental functioning
(measured by SF-12) in that mental health improved with age
(means 43.6, 45.4, & 50.8), depressive symptoms (measured on
CES-D) declined with age (means 22.2, 20.5, & 14.8) and treatment
self-efficacy (measured on the HIV-ASES) improved with age (means
91.3, 96.8, & 100.5).
Conclusion: The oldest group of PLHIV has better mental health
although they are living with multiple comorbidities, perhaps because
they view themselves as survivors. Although fewer older persons have AIDS, 91% are taking HIV medications and their treatment
self-efficacy is significantly higher than the younger age group
(F 9.091, p .000). It might be time to reexamine the possibility of creating peer groups between middle and older aged PLHIV.
D22 - Age
THPDD0205
THPDD0201
Getting older while living with HIV in the United States
1
2
3
4
5
K. Nokes , E. Sefcik , M.O. Johnson , A. Webel , M. Rivero-Méndez ,
J. Voss6, W.-T. Chen7, S. Iipinge8, C.J. Portillo9, I.B. Corless10,
K.M. Sullivan11, L. Tyer-Viola10, J. Kemppainen12, L. Sanzero Eller13,
C. Dawson Rose9, J.C. Phillips14, K. Kirksey15, P. Nicholas16, J. Brion17,
D. Wantland18 and W.L. Holzemer18
1
Hunter College, CUNY, Hunter-Bellevue School of Nursing, New York,
United States. 2Texas A&M University-Corpus Christi, Nursing, Corpus
Christi, United States. 3University of California at San Francisco
San Francisco, United States. 4Case Western Reserve University,
Nursing, Cleveland, United States. 5University of Puerto Rico,
Nursing, San Juan, Puerto Rico. 6University of Washington, Nursing,
Seattle, United States. 7Yale University, Nursing, New Haven, United
States. 8University of Namibia, Nursing, Windhoek, Namibia.
9
University of California at San Francisco, Nursing, San Francisco,
United States. 10MGH Institute of Health Professions, Nursing,
Boston, United States. 11University of Hawaii, Nursing, Honolulu,
United States. 12University of North Carolina Wilmington, Nursing,
Wilmington, United States. 13Rutgers College of Nursing, Nursing,
Cedar Grove, United States. 14University of British Columbia, Nursing,
Vancouver, Canada. 15Seton Family of Hospitals, Clinical Education
Center at Brakenridge, Austin, United States. 16Brigham and
Women’s Hospital and MGH, Global Health, Boston, United States.
17
Duke University, School of Nursing, Durham, United States.
HIV risk and recent sexual behaviour of older adults in rural
South Africa
J. Williams1, F.X. Gómez-Olivé2, N. Angotti1, C. Kabudula2, J. Menken1,
S. Clark3, K. Klipstein-Grobusch4 and S. Tollman2
1
University of Colorado, Institute of Behavioral Science, Boulder,
United States. 2University of the Witwatersrand (WITS), MRC/Wits
Rural Public Health and Health Transitions Research Unit,
Johannesburg, South Africa. 3University of Washington, Seattle,
United States. 4Utrecht University, Global Health Unit, Utrecht,
Netherlands
Presenting author email: jillcolo@colorado.edu
Background: In 20102011 we conducted a HIV and non-communicable disease (NCD) prevalence and risk behavior survey (‘‘Ha Nakekela’’
study) within the Agincourt Health and Demographic Surveillance
System site (AHDSS) in Mpumalanga Province, South Africa (Menken
P.I). We found surprisingly high levels of HIV prevalence at older
ages, given in Table 1.
Women
Men
40 49
50 59
60 69
70 79
80 89
34%
34%
25.5%
33%
12.4%
17%
8%
6%
1%
1%
HIV Prevalence of Older Adults in Agincourt, SA.
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Older adults are either contracting HIV at earlier ages and
surviving for a long period or they are contracting HIV at older ages.
In this study we examine the sexual behavior and HIV risk for older
adults in the two years previous to the study visit.
Methods: The Ha Nakekela study was based on a probability sample
of 7,428 individuals aged 15 years and above. We analyze the sexual
behavior survey for the 2,051 adults over age 39 in the study to
investigate the prevalence of sexual behavior risk factors for
acquiring HIV.
Results: We find evidence suggesting that older adults are at risk
of acquiring HIV through unprotected sex and by having multiple
partners. Fifteen percent of men over 39 report multiple partners,
the majority of whom are significantly younger. Very few men (9.5%)
and women (11.5%) reported condom use at last sex. We also find
that older adults are not likely to know their or their partner’s HIV
status: only 5% of sexually active older adults said they knew the HIV
status of their sexual partner. Of those that are HIV positive, 31% had
never been tested and only 40% of those that had ever tested
reported being on ART.
Conclusion: The high HIV prevalence, lack of condom use, lack of
testing, and low ART uptake of known positives suggests that older
adults are an over-looked but critical population for both HIV
prevention and treatment programs.
THPDD0207
Determining the healthcare needs of older people living
with HIV in Uganda: a qualitative study
M. Kuteesa1,2
Uganda Cares-AIDS Healthcare Foundation, Clinical Care, Kampala,
Uganda. 2University of Sydney, School of Public Health, Sydney,
Australia
Presenting author email: monakello@gmail.com
1
Background: HIV/AIDS among adults 50 and older in Uganda is on
the increase partly due to newly diagnosed infections in this age
group as well as improved survival owing to antiretroviral therapy,
for many HIV infected persons. Although national programmes are in
place to ensure access to medical services, older people living with
HIV have unique unmet healthcare needs. The objectives of this
study were to identify the healthcare needs of older Ugandans living
with HIV and to gather recommendations for improvements by
health service providers.
Methods: Data regarding healthcare needs were collected from HIV
positive adults aged 50 years and older attending two large nongovernmental outpatient clinics in Kampala and Masaka districts,
Uganda between March 2011 and June 2011. Individual
in-depth open-ended qualitative interviews focus group discussions
were conducted. Observations of clinic interactions were also
recorded. Interview transcripts were analyzed using thematic content analysis.
Results: The mean age of the respondents was 65 years, 50% were
female, (n 40). Respondents expressed multiple age-related healthcare needs that may differ from their younger counterparts. Needs
increased with higher age. Both men and women attributed double
stigma from HIV and old age as a major factor affecting disclosure
and seeking healthcare for HIV. 60% of the respondents expressed
anxiety about their future access to healthcare, the lack of social
services and end of life care. Lack of transport and food access issues
compromised respondents’ adherence to antiretroviral therapy.
Conclusion: Older people living with HIV have unique healthcare
needs which health promotion programmes should consider meeting
through appropriate and innovative approaches such as preventing
Track D Social Science, Human Rights and Political Science
and managing age-related chronic illnesses, palliative care, developing age-friendly services and settings. Research to further explore the
impact of these healthcare needs on the quality of life of older
PLWHA is required.
D23 - Incarceration
WEAD0605
Prevalence of transmissible infections and
socio-demographic and behavioral risk factors
amongst prisoners in Mexico City: a cross-sectional
study of 17,296 inmates
S. Bautista-Arredondo
National Institute of Public Health, Cuernavaca, Mexico
Presenting author email: sbautista@insp.mx
Background: The health of prisoners is an issue of global concern.
Increased socio-demographic and behavioural risk factors prior to
incarceration and poor prison living conditions contribute to increased prevalence of transmissible infections. Little is known about
the health of prisoners in Mexico City. This study sought to establish
prevalence data and risk factors to identify those currently needing
healthcare and to inform future policy.
Methods: This cross-sectional study was carried out in 4 Mexico City
prisons, June to December 2010. Ethical approval was granted prior
to starting; participation was voluntary, confidential and based on
informed consent.
Participants were offered HIV, Hepatitis B, C and Syphilis testing.
A representative sample completed a questionnaire on sociodemographic characteristics and risk behaviours. Positive results
were delivered with counselling and treatment or referral with
consent. Data was analysed using Stata.
Results: 76.8% (15,517/20,196) men and 92.9% (1,779/1914)
women participated. Complete data sets were available for 98.8%.
Prevalence of HIV (0.7%), syphilis (Anti-TP Ab 4.1%; VDRL 2.0%),
Hepatitis B (HBcAb 3.0%; HBsAg 0.2%) and Hepatitis C (3.2%) was
higher in the study population compared with national data. The
relative increase was greater for HIV and syphilis amongst women,
Hepatitis C in men, and all infections in younger participants.
Questionnaire data (1934 men, 520 women) demonstrated lower
educational levels, increased smoking and substance use compared
to national data. High levels of unsterile tattoing, physical abuse and
a history of sexual violence were found.
Conclusion: The study identified that health screening is acceptable to
Mexico City prisoners and feasible on a large-scale. It demonstrated
increased prevalence of HIV and other infections compared to
national data, though low rates compared to international data.
Individual participants benefited from earlier diagnosis, treatment
and support. The data collected will also enable the formation of
improved policy for this vulnerable group of individuals.
D24 - Those growing up with HIV
MOAD0103
The challenges of care and support for a generation of
nosocomially infected young adults from Romania living
with HIV
185
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Track D Social Science, Human Rights and Political Science
F. Lazar and D. Buzducea
University of Bucharest, Social Work, Bucharest, Romania
Presenting author email: florin.lazar@sas.unibuc.ro
of children infected, affected and unaffected
by HIV
Background: After two decades of living with HIV a generation of
around 7,000 children from Romania nosocomially infected in
communist era, turned into young adults. Hyper protection from
the family, combined with discrimination in education services,
developing social services, and a focus on medical aspects represented the environment these children grew. Between 2004 and
2010 the Global Fund financed social programs for their professional
integration, increasing the percentage of those availing of cash
benefits from 30% to 66%. In 2010 people living with HIV (PLHIV) and
NGOs protested over ARV treatment interruptions and budgetary
cuts due to economic crisis, although WHO estimated the treatment
coverage at 83% in 2009.
Methods: A nationally representative clinic-based research among
PLHIV was carried out in 2011 (MarchJune) to determine their
access to treatment, care and support (N 618, 94%).
Measures of treatment interruptions, adherence and access to
services were included, as well as demographics variables. Sample
was weighted according to subjects’ surveillance center
registration.
Results: The vast majority of the sample (71.7%) is young (1824
years), with more than 6 years of known seropositivity (82.1%),
receiving ARV for more than 6 years (78.7%), with more than
2 changes in their treatment plan (80.1%), and with their main
source of income as cash benefits (80.5%). Unintended treatment
interruptions were spread (65.2%, average interruption lasting 38
days), resulting in more visits to regional center (49.2% more than
once a month), higher expenses and the need for new combinations
of ARV. Discontinuous adherence was reported by 42.2%. Access to
social services was high (over 80%).
Conclusion: While Romania is a low prevalence country, and ensures
high coverage of ARV treatment, authorities must pay attention at
continuous treatment access for PLHIV, and support of treatment
adherence to prevent deterioration of the health status and ensure
universal access for PLHIV.
D26 - Caregiving
MOAD0301
Mental health and substance use problems among a
sample of African American and Latina caregivers
E.K. Santamaria1, K.S. Elkington1, S. Alicea2, C. Dolezal1, C.-S. Leu1 and
C.A. Mellins1
1
HIV Center for Clinical & Behavioral Studies,
New York State Psychiatric Institute and Columbia University,
New York, United States. 2New York University Steinhardt
School of Education, Applied Psychology, New York
United States
Presenting author email: santamar@nyspi.columbia.edu
Background: Despite evidence that a significant number of children
infected and affected by HIV (uninfected, but have HIVfamily
member) reside with caregivers who are not their birth parent, few
studies have examined the psychological functioning of these
alternate caregivers. The majority are women, typically ethnic
minorities, often from impoverished communities. This study
compares mental health and substance use problems in birthmothers, and non-birth female caregivers of HIV-infected, affected,
and unaffected children in the US.
Methods: Data come from the baseline caregiver interviews of two
longitudinal studies of urban youth perinatally-HIV infected, HIVaffected, and unaffected by HIV. Caregivers (n 451) included HIV
and HIV birth-mothers and other HIV female caregivers
primarily of African American and Latina ethnicity. Measures of
depression and anxiety symptoms and substance use problems were
completed.
Results: Birth-mothers reported more symptoms of depression (pB
.001) and anxiety (p B .001) than non-birth caregivers. Non-birth
caregivers were less likely (3%) to report substance use than HIV
(13%) or HIV (12%) birth-mothers (p .006) (Table 1). In multiple
regression analyses, HIVbirth-mothers, but not HIVbirth
mothers were significantly more depressed and anxious than nonbirth caregivers, after adjusting for age, race, number of children
under 18-years, and having a partner in home (Table 2). Both birthmother groups (HIV and HIV ) had more substance use
problems than non-birth caregivers even after adjusting for
covariates. Among all caregivers in the study, those who reported either substance use or Latina ethnicity had significantly
higher depression and anxiety scores (each p5.01; data not
shown).
Conclusion: Data support previous studies that HIV birth-mothers
have worse mental health outcomes than non-birth caregivers,
warranting the development of efficacy-based interventions for this
population. However, the data also indicate the vulnerability of
inner-city HIV birth-mothers, and the need for mental health
Table 1. Caregiver characteristics
HIV Birth Mother
N (%)
209 (46)
HIV Birth Mother
120 (27)
HIV Non-birth Caregiver
Chi-square/Anova p-value
122 (27)
Age (mean)
39.2
38.3
54.4
.000
African-American (%)
55
37
57
.006
Latina (%)
33
48
35
Children B18 years in home (mean)
Partner at home (%)
2.5
39
2.9
34
2.5
38
.014
.723
Depression (mean)
10.8
8.8
6.6
.000
Anxiety (mean)
20.2
19.3
13.6
.000
Substance use (%)
13
12
3
.006
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Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Table 2.
Track D Social Science, Human Rights and Political Science
Regressions-mental health/substance use
Depressiona
Anxietya
Substance Useb
b (p)
b (p)
OR (p)
HIV Birth Motherc
.247 (.001)
.272 (.000)
5.97 (.015)
HIV Birth Motherc
.013 (.853)
.103 (.142)
5.00 (.039)
Age
.002 (.977)
.027 (.671)
1.00 (.981)
Race/Ethnicity
.244 (.000)
.256 (.000)
.710 (.324)
.024 (.628)
.020 (.689)
.885 (.388)
.158 (.001)
.113 (.022)
Children B18 years in home
Partner at home
1.11 (.761)
a
Linear regression; bLogistic regression; cHIV Non-birth Caregivers are the reference category.
services among caregivers with a history of substance use or of
Latina ethnicity.
MOAD0303
D27 - Disability
FRLBD03
Gendered violence, gender inequalities and home-based
care: the forgotten relationship of power
The impact of depression on retention in care and viral
suppression in a large cohort of insured HIV-infected
patients
A. Gibbs1, L. Washington2 and N. Mbatha2
1
University of KwaZulu-Natal, Health Economics and HIV/AIDS
Research Division (HEARD), Durban, South Africa. 2Project Empower,
Durban, South Africa
Presenting author email: gibbs@ukzn.ac.za
R.C. Hechter1, J.Q. Wang1, M.A. Sidell1 and W.J. Towner2
1
Kaiser Permanente Southern California, Research and Evaluation,
Pasadena, United States. 2Kaiser Permanente Southern California,
Infectious Disease, Los Angeles, United States
Presenting author email: rulin.c.hechter@kp.org
Background: Women’s low or unpaid role in providing care for people
living with HIV in the form of home-based care while central to the
response to HIV been has increasingly been recognised as entrenching
unequal gender relationships. Frameworks to map out the pathways
have suggested that this process occurs in three domains: financial
costs, opportunity costs and physical and emotional costs. Yet
such a framework has a tendency to ignore the broader
conceptualisation of gender inequalities that include violence against
women.
Methods: We undertook 5 focus groups with 45 home-based carers
in South Africa as part of a larger study focused on how to transform
home-based care organisations from spaces of reproducing inequalities to transforming gender relationships. We conducted thematic
analysis on the data exploring factors that could support or hinder
gender equality.
Results: As with other studies, our data showed home-based carers
suffered economic costs related to their work, often spending their
own money to provide for their patients. In addition, few received
stipends or other financial support either from donors, government
or NGOs. Many carers also related the extreme physical and
emotional costs of the work they did; again reflecting what is
already known about providing care. However, home-based carers
also spoke about the central role of gender-based and sexual
violence that they feared, risked and experienced both while
working and sometimes within the organisations they worked in.
Such relationships of violence undermined their ability to envision their work as spaces for women’s empowerment and
transformation.
Conclusion: To move women’s participation in home-based care
from one of reinforcing gender inequalities to empowering women
requires those supporting home-based carers to envision a wider
conceptualisation of the gender inequalities home-based carers face,
that includes the centrality of gender- and sexual-violence, and
actively work to programme and tackle these.
Background: Psychiatric disorders are prevalent among HIV-infected
individuals and may have deleterious effects on HIV care and
outcomes. We sought to examine the impact of depression on
retention in care and viral suppression among racial/ethnical diverse
HIV-infected patients in a large managed care organization.
Methods: We evaluated a cohort of HIV- infected adults who
received care and had at least 8 months’ membership in health
care plan in 2010 in Kaiser Permanente Southern California. History
of depression prior to 2010 was identified by International Classification of Diseases, Ninth Revision Clinical Modification (ICD-9 CM)
codes for depressive symptoms. Retention in care was defined as
] 2 CD4 and/or HIV-1 RNA tests at least 90 days apart in 2010.
Viral suppression was defined as undetectable viral load or HIV-1
RNA B50 copies/mL at the last test in 2010 while on antiretroviral
therapy (ART). In multivariable analyses, Poisson regression with
robust error variances was used to estimate rate ratios (RR) and 95%
confidence intervals (CI) for retention and logistic regression was
used to estimate odds ratios (OR) for failure of viral suppression,
adjusted for age, gender, race/ethnicity, mode of HIV infection, ever
AIDS diagnosis, and medical center of care.
Results: Among 6,455 patients (90% men, 49% white), 51% had a
history of diagnosed depression, and 77% were retained in care.
Among 4403 patients on ART with ] 1 viral load measurement, 86.3%
were virally suppressed. In multivariable analysis, patients with
depression were less likely to be retained in care (RR 0.89, 95%
CI 0.860.91). In stratified analysis by gender, the adverse impact of
depression on retention appeared to be larger among women
(RR 0.82, 95% CI 0.750.89) than among men (RR 0.89, 95%
CI 0.870.92). Depression was significantly associated with increased risk of failure of viral suppression (OR 1.25, 95%
CI 1.041.49). In stratified analysis, depression appeared to be
associated with increased risk of failure of viral suppression among
women (OR 2.65, 95% CI 1.305.39) than among men (OR 1.15,
95% CI 0.961.38), and the adverse impact appeared to be larger
187
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
among patients who were not retained in care (retained: OR 1.20,
95% CI 0.991.45; not retained: OR 1.37, 95% CI 0.832.27).
Conclusion: Depression was prevalent in this cohort and worsened
retention and viral control. Retention in care may modify the adverse
impact of depression on viral suppression. Interventions are needed
to alleviate depression and thus enhance retention and improve
HIV outcomes.
D29 - Sexualities: meanings, identities,
norms and communities
WEAD0101
A longitudinal in-depth study of gender-specific experiences
in antiretroviral treatment patients in South Africa
K. de Wet1 and E. Wouters2
1
Univiversity of the Free State, Sociology, Bloemfontein, South Africa.
2
University of Antwerp, Antwerp, Belgium
Presenting author email: dewetk@ufs.ac.za
Background: Previous research (amongst others our own published in
AIDS and Social Science & Medicine) has demonstrated gender
differences in various antiretroviral treatment (ART) outcomes including, adherence, quality-of-life, disclosure and retention. However,
little longitudinal, in-depth research has been done to investigate the
why and how of these differences.
The current study firstly aims to explore the impact of masculinity
and femininity on ART experiences, in both a longitudinal and
in-depth manner. In addition, the study investigates the complex
interrelationships between gender constructs whereby males
and females potentially influence-through intricate household dynamics- the ART experiences of the other gender.
Methods: Based on a previous explorative quantitative study, we
conducted a longitudinal qualitative study whereby 12 male and 12
female ART patients were repeatedly interviewed >over the course
of 1 year in the Free State province of South Africa.
Results: Despite several cases of lipodystrophy and other side-effects
among women due to ART, they seem to adhere and lead healthy
lifestyles, often in the absence of a male partner. Male patients
reported a clear notion of masculinity that required males to be in
control and act strong, highly sexual and economically productive,
thus conflicting with the role of ‘good patient’ that is expected to
accept being HIV-positive, take instructions, and engage in healthenabling behaviors. The majority of men interviewed overcame these
barriers and internalized their treatment, albeit with fewer sideeffects and more support in terms of reminding and accompanying
them to the clinic (mostly by females).
Conclusion: The study findings have both theoretical and practical relevance. Theoretically, the longitudinal impact of gender and
household dynamics on the ART career draws attention to the
sociological processes influencing ART outcomes. Practically, the
study demonstrates that policy interventions aimed at improving
long-term ART outcomes should incorporate the (interactions
between) gender-specific illness and treatment experiences.
FRLBD06
‘Privileging the personal’: mobilising marginalised identities
and voices in the context of HIV health promotion with
’’hard to reach’’ migrant and second generation Asian gay
Track D Social Science, Human Rights and Political Science
men in Metropolitan Sydney, Australia; a resource
development and community building initiative
M.F. Teh
ACON Health, Community Development, HIV Education (Asian Gay
Men’s), Sydney, Australia
Presenting author email: mteh@acon.org.au
Background: Asian gay men make up the highest group in MSM/gay
HIV notification after Anglo background, constituting a priority group
for HIV health promotion in Australia (MHAHS, 2011). Multiple
challenges exist as issues of stigma, migration, isolation, in addition
to sexual stereotyping and homophobia within the gay and ethnic
communities respectively, complicates this work.The immediacy of
these issues renders HIV health promotion a second order issue.
Underrepresentation in HIV health promotion work, research and
general media also contributes to their invisibility.
Multicultural HIV & Hepatitis C Service (MHAHS). Trends in NSW
HIV notifications 19992010. (unpublished).
Methods: The ‘‘A-Men’’ publication was developed with an aim to
engage lived experiences and visibility of Asian gay identities as an
entry point to promoting sexual health and wellbeing. The approach
was two-pronged: a resource production engaging broader issues
facing Asian gay men - the person-centric approach; and the
developmental process that involves and builds community ownership - ‘for the community, by the community’. With $5000 community
arts funding from Sydney city council, the resource was developed
and distributed in-print and online.
Results: A total of 70 volunteers from 9 different Asian ethnicities
were involved in the production.1000 hard-copies were launched in
March and distributed through community and service providers.
1600 users accessed the online version to date. Volunteer feedback
(n 58) showed increased social-connectedness, self-esteem, pride,
HIV awareness and knowledge of services. 2 community focus groups
(n 62)reported similar trends: greater community engagement
and dialogue around wellbeing and self-esteem.
Conclusion: A broader exploration of lived realities was effective in
enlivening HIV messaging with Asian gay men. Through engaging
intersections of identity, art and community building, a ‘biggest bang
for your buck’ can be achieved in a resource limited setting. Through
cultural change, "A-Men" addressed the barriers to HIV awareness and wellbeing, in the process building a more resilient and
empowered community.
D30 - Sexual minorities and HIV
vulnerability and/or resilience (e.g., gay
and other men who have sex with men
(MSM), lesbians and other women who
have sex with women (WSW), bisexuals,
transgenders, transsexuals
THAD0504
Relationship between comfort with and disclosure about
sexual orientation on HIV-related risk behaviours and HIV
testing among men who have sex with men in Beirut,
Lebanon
G.J. Wagner1, F.M. Aunon1, Y. Rana1, D. Khouri2 and J. Mokhbat2
1
RAND Corporation, Health, Santa Monica, United States. 2Lebanese
AIDS Society, Beirut, Lebanon
Presenting author email: faunon@rand.org
188
Abstracts of the XIX International AIDS Conference
Journal of the International AIDS Society 2012, 15 (Suppl 3)
Background: Evidence suggests that men who have sex with men
(MSM) account for most new HIV infections in Lebanon and act as a
bridge to transmission in the general population. In a region where
same-sex sexual activity is highly stigmatized, a better understanding
of the psychosocial factors that influence sexual risk behavior and HIV
testing in MSM is essential for HIV prevention initiatives to be
effective.
Methods: An exploratory, qualitative study was conducted with a
sample of 31 MSM living in Beirut. Semi-structured interviews
examined relationships with family and friends, comfort with and
disclosure of sexual orientation, sexual behavior, and HIV testing.
All interviews were recorded, transcribed, and coded in Atlas-ti to
identify themes and extract counts.
Results: All men self-identified as homosexual (77.4%) or bisexual
(22.6%), although 32.3% also have sex with women, and a majority
(64.5%) reported some discomfort with their sexual orientation.
The men described a strong heterosexual social norm, causing some
to feel guilty and lead a ‘‘double life’’ where they conceal their
sexual orientation by publically feigning attraction or dating women,
or dissociating from effeminate men. Comfort with and disclosure
about sexual orientation appeared to be linked with sexual
risk behaviors and HIV testing. As compared to the remaining
sample (n 18), the 13 participants who were both uncomfortable
with their sexual orientation and had not disclosed to either
parent reported higher rates of unsafe sex (69.2% versus
33.3%), more annual sexual partners (mean36.7 versus 17.0),
and lower rates of being HIV-tested (53.8% versus 88.9%)
and discussing HIV risk with their sex partners (38.5% versus
88.9%).
Conclusion: These findings reveal the influence of sexual identity
acceptance and disclosure on condom use and HIV testing in the
context of high societal stigma, and suggest the need for HIV
prevention interventions to facilitate progression through these
psychosocial processes of sexual development.
FRLBD05
An MSM-specific definition of intimate partner violence
includes HIV-related violence and is associated with sexual
risk-taking among MSM
R. Stephenson and C. Finneran
Emory University Rollins School of Public Health, Hubert Department
of Global Health, Atlanta, United States
Presenting author email: cafinne@emory.edu
Background: Evidence indicates that MSM experience higher rates of
intimate partner violence (IPV) than non-MSM; however, no study
has examined what defines IPV among MSM, or the associations
between MSM-specific IPV and sexual risk-taking
Methods: Seven focus group discussions were held with 84 MSM,
generating 30 types of IPV, including HIV-specific IPV. These were
tested using a cross-sectional survey of 1,074 MSM. Factor analysis
generated five domains of MSM-specific IPV, including a domain of
HIV-related IPV. Six logistic regression models for unprotected anal
intercourse (UAI) were created (n 626). Models controlled for age,
race, education, employment, HIV status, and gay identity, with the
key covariate being receipt or perpetration of three different IPV
measurements: MSM-specific, Conflict Tactics Scale (CTS), and World
Health Organization (WHO).
Results: The MSM-specific IPV definition included HIV-specific
typologies of violence not currently included in any definition of
IPV, e.g., not disclosing HIV-positivity to a partner, and captured
significantly higher reporting of IPV compared to WHO (46.2% v.
13.5% receipt of IPV; 31.9% v. 8.5% perpetration of IPV). Reporting
Track D Social Science, Human Rights and Political Science
receipt of neither WHO-defined IPV nor CTS-defined IPV was
significantly associated with UAI, but reporting receipt of MSMspecific IPV significantly increased odds of UAI (OR: 1.80, 95% CI:
1.27, 2.54). Two models demonstrated a significantly increased risk of
UAI among men reporting IPV perpetration (WHO OR: 1.74, 95% CI:
0.91, 3.31; CTS OR: 1.67, 95% CI: 1.06, 2.63; MSM-specific OR: 1.82,
95% CI: 1.26, 2.64).
Conclusion: This study provides for the first time a MSM-specific
definition of IPV that captures HIV-related violence not represented in standard definitions. MSM who reported MSM-specific
IPV had increased odds of UAI at last sex. These findings suggest
that MSM experiencing IPV are at higher risk for HIV seroconversion, although this association may not be recognized by using nonMSM-specific definitions of IPV that do not include HIV-related
violence.
D31 - Effects of homophobia and
transphobia
THAD0505
Internalized homophobia and transphobia, low self-esteem
and non-disclosure of sexual identity as factors contributing
to HIV vulnerability of men who have sex with men (MSM),
transgenders and hijras: experience from the Global Fund
supported Pehchān program in India
S. Shaikh1, S. Lonappan2, G. Kumarikunta3, K. Biswas3, S. Rakesh4,
A. Aher1, S.M. Mehta5 and J. Robertson6
1
India HIV/AIDS Alliance, Pehchan, New Delhi, India. 2India HIV/AIDS
Alliance, Communications, New Delhi, India. 3India HIV/AIDS Alliance,
Monitoring & Evaluation, New Delhi, India. 4India HIV/AIDS Alliance,
Technical Support, New Delhi, India. 5India HIV/AIDS Alliance,
Policy & Programmes, New Delhi, India. 6India HIV/AIDS Alliance,
New Delhi, India
Presenting author email: ssimran1888@gmail.com
Background: HIV prevalence among MSM in India remains disproportionately high at 7.4% as compared with overall national
prevalence of 0.3%. India HIV/AIDS Alliance in consortium with five
other organizations implements the five-year Global Fund-supported
Pehchān program in 17 Indian states to build the capacity of 200
CBOs to serve as effective HIV prevention partners with the National
AIDS Control Program and reach 453,750 MSM, transgenders and
hijras using a community-driven and rights-based approach. Nondisclosure of identity and low self-esteem due to internalized stigma
are known to be associated with vulnerabilities that place these
populations at greater risk of HIV infection.
Methods: A cross-sectional baseline study sampled 2,762 MSM,
transgenders and hijras (TG/H: 16%) in 55 districts across 10 states to
understand demographics, behavior and needs of target populations.
Time and Location Cluster Sampling (TLCS) was used to identify these
often hard-to-reach and relatively mobile populations. Data were
analyzed using SPSS.
Results: Self-disclosure of sexual identity occurred least with parents
(21%) for reasons ranging from fear of being rejected and rendered
homeless to adverse legal consequences. Self-disclosure with siblings
was also low (22%), for fear of being neglect, isolation, and verbal/
physical abuse. Disclosure was highest amongst community peers
(67%). Feelings of shame (33%),