Is bacterial vaginosis just the tip of the
iceberg as to the risk of HIV related
to vaginal flora abnormalities ?
Presenter: Guédou F. A. MD, MSc, PhD
Co-authors: Van Damme L, Mirembe F, Solomon S, Becker M,
Deese J, Crucitti T, Taylor D, Alary M
Afri-Can Forum
Entebbe 17-19 January 2013
1
Overview
 Background
 Objectives
 Methods and materials
 Results
 Discussion
 Conclusion
2
Background(1)
 Bacterial Vaginosis (BV) is a polymicrobial infection
resulting from the replacement of lactobacilli of the
normal vaginal flora by a variety of bacteria,
predominantly anaerobic
 The main challenge of BV to date is that of the
identification of its causative agent so that the current
consensus is that a polymicrobial infection
3
Background (2)
Conventionally, BV is diagnosed:
 Clinically on Amsel’s criteria;
 Biologically with Nugent’score:
 normal flora (NS = 0-3);
 intermediate flora (NS = 4-6);
 BV (NS = 7-10)
4
Background (3)
 BV = most common genital infection worldwide
 Higher prevalence in developing countries (DC):
between 9% and 50%; 70% among female sex
workers (FSW)
5
Background (4)
 But what justifies the present work is that the role of BV
in HIV acquisition or transmission has been strongly
suggested by some studies
 Since BV has such a high prevalence among FSWs, even
a modest RR
substantial attributable risk for HIV
Background (5)
 This is of uppermost interest when considering the role of
core group played by FSWs in the dynamic of HIV
epidemics in DC and particularly in Sub-Saharan Africa
 In addition, most studies that have examined this
association have classified “BV” as (BV vs. non-BV)
 Very little attention has been paid to the possible role of
intermediate vaginal flora (IVF) in this association
7
Objectives
 To investigate the association between HIV and
respectively IVF and BV, among FSW screened prior
to enrolment in the Cellulose sulfate trial
 To compare the strengths of these two associations
8
Materials and Methods (1)
Settings: Sites of the CS trial
Chennai
Mudhol/Jhamkandi
(India): (2)
Benin
Uganda
Kampala
(Uganda): (1)
Cotonou (Benin): (1)
Durban (South Africa): (1)
Materials and Methods (2)
Participants selection: Eligibility criteria:
 Potential participant in the SC trial
 18 years or older
 HIV high risk woman (≥ 3 different sexual partners
in the last 3 months and ≥ 3 sexual acts/week)
 Data available for both BV and HIV
 Informed consent for screening
Materials and Methods (3)
Data collection
 Interview: socio-demo. and behavioral data
 Gynecological Exam: clinical data
 Blood and cervico-vaginal swabs:
 HIV: HIV antibodies test
 BV: Gram and Nugent score (NS)
 Gonorrhea and Chlamydia: SDA (Strand DNA Amplification)
 Syphilis: RPR confirmed with TPHA
 Trichomoniasis (TV) and Candidiasis: Wet mount
Materials and Methods(4)
Statistical analyses
 Log binomial regression to model HIV prevalence
with respect to vaginal flora abnormalities:
 2 categories: BV vs. Non-BV
 3 categories : normal (reference), IVF and BV
(Comparison of BV and IVF prevalence ratios)
 Bivariate analyses (controlling for site)
 Multivariate analyses (adjustment)
12
Results: (1)
Characteristics of 1367 FSW screened at 2 African and 2 Indian sites of a
randomized microbicide clinical trial on cellulose sulfate gel
Characteristics
Number of sexual partners /last 3 months
Number of sexual acts / last 7 days
Condom use at the last sexual act
Intra-vaginal cleansing
Current STI or lower genital infections:
HIV
Gonorrhea
Chlamydia
Trichomoniasis
Candidiasis
Bacterial vaginosis
Intermediate vaginal flora
Syphilis
n or median (%) ou IQR
80 [25 – 270]
8
[4 – 20]
1061
(77.7)
1340
(98.0)
369
111
80
92
421
651
262
82
(27.0)
(8.1)
(5.9)
(6.7)
(30.8)
(47.6)
(19.2)
(6.0)
13
Results (2)
Multivariate analysis between vaginal flora abnormalities and HIV
Factors
HIV prevalence Ajusted prevalence ratio
by exposition
(aPR)*
level
ni/Ni
(%) aPR (95%CI)
p-value
Vaginal flora abnormalities (in 2 cat.):
Bacterial vaginosis (NS= 7-10)
Non-Bacterial vaginosis (NS= 0-6)
192/651 (29.5)
177/716 (24.7)
1.21 (1.03-1.44) 0.02
1.00
–
–
Vaginal flora abnormalities (in 3 cat.):
Bacterial vaginosis (NS= 7-10)
Intermediate vaginal flora (NS= 4-6)
Normal vaginal flora (NS= 0-3)
192/651 (29.5)
84/262 (32.1)
93/454 (20.5)
1.48 (1.20-1.84) 0.0003
1.56 (1.22-1.98) 0.0003
1.00
–
–
*The aPR from the 2 types of categorisation were obtained from separate multivarite
models but including the same covariates (site, education level, STI history, occupation
other than Sex work, oral sex, female sterilisation, gonorrhea and vaginal candidiasis)
14
Discussion (1)
• The aPR obtained using women with NVF as reference was
substantially higher than that obtained using women without BV
as reference
• This is due to the fact that HIV prevalence among women with
IVF was significantly higher than that of women with NVF: aPR
= 1.56 (95% CI = 1.22-1.98, p = 0.0003)
• The use of all women without BV (NVF/IVF) as a reference to
measure the increase in HIV risk associated with BV could lead
to its underestimation
15
Discussion (2)
 In addition, the strength of the association obtained with
IVF was similar to that obtained with the BV (p = 0.6347)
 This is in contrast with the trend of monotonic increase
found in most studies that have examined the association
between HIV and vaginal flora abnormalities
16
Discussion (3):
Direction of the association?
 BV may increase the risk of HIV
Mobilization of HIV target cells
Weakening of the vaginal epithelial barrier
 HIV may increase the risk of BV
Immunosuppression? But no significant association
between HIV and other STIs!
 A risk factor common to HIV and BV (not / insufficiently
controlled by analysis)
17
Discussion (4): the study limits
 Cross-sectional design
 124 eligible FSW excluded (lack of data on BV)
 Inability to control for HSV-2, alcohol
 Possibility of inaccuracy for some data:
 Vaginal douching (quantification)
 Number of sexual partners (memory)
 Condom use (social desirability)
18
Discussion (5): Strenghts of the study
 Clinical trial settings:
 Large sample size
 An international quality control system
 Use of the current gold standard for BV diagnosis
 Use of log-binomial regression: which enabled a better
approximation of the relative risk
19
Conclusions
 The results of this study suggest that:
 BV represents only a part of the vaginal flora
abnormalities associated with an increased risk of HIV;
 IVF is associated with HIV as stronger as BV
 Need of prospective studies to confirm findings
 Implication for HIV prevention:
Controlling vaginal flora abnormalities (not just BV) among
FSWs may be an untapped strategy to curb HIV epidemic,
particularly in countries with concentrated epidemic
20
Acknowledgments (1)
 Trial participants
 Cotonou Team (Benin):
 Clinical team: I. Minani; N. Geraldo; G. Ainan; C. Assogba; C. Gbenafa
 Lab team: M. Loembe; E. Goma; G. Ahotin; L. Djossou; N. Tata
 Sociology team: O. Azonnadou, J. Agonmounon, F. Mito-Yobo
 Field team: G. Batona et coll.
 Canada Team(CHU of Quebec) : M. Belleau, J. Leroux, J. Begin, L.
Pagé
 Other sites:
 Lusaka (Ouganda): F. Mirembe et al.
 Chennai (Inde): S. Solomon et al.
 Mudhol/Jhamkandi (Inde): M. Becker et al.
21
Aknowledgments (2)
 International Team:
 CONRAD (VA, USA): L. Van Damme (PI);
 FHI (NC, USA): J. Deese; D. Taylor;
 ITM (Antwerrp, Belgium) : T. Crucitti
 Sponsor: CONRAD (USA)
 Funders:
 USAID
 Fondation Bill Gates & Melinda
22
Thanks for your
kind attention