Nevirapine Mother-to-child Transmission Bibliography
Albrecht, S., K. Semrau, P. Kasonde, M. Sinkala, C. Kankasa, C. Vwalika, G. M.
Aldrovandi, D. M. Thea, and L. Kuhn. 2006. "Predictors of nonadherence to
single-dose nevirapine therapy for the prevention of mother-to-child HIV
transmission." J Acquir Immune Defic Syndr, 41(1):114-8.
BACKGROUND: Adequate adherence is required for prevention of mother-to-child transmission of HIV
(pMTCT) programs to be effective. We investigated predictors and extent of nonadherence to single-dose
nevirapine. METHODS: Data on nevirapine intake and possible predictors were collected among 760 HIVpositive women with liveborn babies enrolled in a study in Lusaka, Zambia. RESULTS: Most (94%) women
took nevirapine before delivery, and most (91%) newborns received it soon after delivery. Maternal
nonadherence was associated with home births (odds ratio [OR]: 3.2; 95% confidence interval [CI]: 1.3 to
7.4), no high school education (OR: 2.4; 95% CI: 1.1 to 5.3), and low newborn birth weight (OR: 4.6; 95% CI:
1.3 to 20.1). Disclosure of HIV status and couples counseling was only associated with adherence among
home births. Failure to administer nevirapine to the newborn was associated with birth at the tertiary hospital
(OR: 7.2; 95% CI: 3.7 to 13.8), lower 5-minute Apgar scores (OR: 0.5; 95% CI: 0.4 to 0.7), and neonatal
death (OR: 5.8; 95% CI: 2.0 to 16.3). CONCLUSIONS: Excellent adherence to single-dose nevirapine for
pMTCT can be achieved. Nonadherence seems to be affected by place of birth and by poor health status of
the newborn. Procedures to ensure that viable yet ill neonates receive nevirapine should be part of clinical
protocols and training within pMTCT programs.
Brentlinger, P. E., C. B. Behrens, and M. A. Micek. 2006. "Challenges in the concurrent
management of malaria and HIV in pregnancy in sub-Saharan Africa." Lancet
Infect Dis, 6(2):100-11.
Approximately one million pregnancies are complicated by both malaria and HIV infection in sub-Saharan
Africa annually. Both infections have been associated with maternal and infant morbidity and mortality.
Intermittent preventive treatment, usually with sulfadoxine-pyrimethamine, has been shown to prevent
pregnancy-related malaria and its complications. Several different regimens of antiretroviral therapy are now
available to prevent mother-to-child transmission of HIV and/or progression of maternal HIV infection during
pregnancy. However, no published studies have yet shown whether standard intermittent preventive
treatment and antiretroviral regimens are medically and operationally compatible in pregnancy. We reviewed
existing policies regarding prevention and treatment of HIV and malaria in pregnancy, as well as published
literature on adverse effects of antiretrovirals and antimalarials commonly used in pregnancy in developing
countries, and found that concurrent prescription of sulfadoxine-pyrimethamine, co-trimoxazole
(trimethoprim-sulfamethoxazole), and antiretroviral agents including nevirapine and zidovudine per existing
protocols for prevention of malaria and vertical HIV transmission may result in adverse drug interactions or
overlapping, diagnostically challenging drug toxicities. Insecticide-treated bednets should be provided for
HIV-infected pregnant women at risk for malaria. Sulfadoxine-pyrimethamine should be prescribed
cautiously in women concurrently receiving daily nevirapine and/or zidovudine, and should be avoided in
women on daily co-trimoxazole. Further research is urgently needed to define safe and effective protocols
for concurrent management of HIV and malaria in pregnancy, and to define appropriate interventions for
different populations subject to differing levels of malaria transmission and antimalarial drug resistance.
Chaix, M. L., D. K. Ekouevi, F. Rouet, B. Tonwe-Gold, I. Viho, L. Bequet, G. Peytavin,
H. Toure, H. Menan, V. Leroy, F. Dabis, and C. Rouzioux. 2006. "Low risk of
nevirapine resistance mutations in the prevention of mother-to-child transmission
of HIV-1: Agence Nationale de Recherches sur le SIDA Ditrame Plus, Abidjan,
Cote d'Ivoire." J Infect Dis, 193(4):482-7.
The frequency of resistance mutations was estimated in the cohort of Agence Nationale de Recherches sur
le SIDA Ditrame Plus, a study that evaluated the combination of short-course zidovudine (ZDV) plus
lamivudine (3TC) and single-dose nevirapine (SD-NVP) followed by 3 days of postpartum ZDV plus 3TC for
Page 1 of 56
the prevention of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1). The
frequency with which resistance mutations were detected in mothers at week 4 postpartum was 1.14% (95%
confidence interval [CI], 0.03%-6.17%) for NVP and 8.33% (95% CI, 3.66%-15.76%) for 3TC. In multivariate
analysis, 3TC resistance was associated with a longer duration of ZDV plus 3TC prepartum prophylaxis
(P=.009). This regimen, which is feasible in resource-limited settings, prevents most peripartum HIV-1
transmission and minimizes the development of NVP resistance.
Eley, B. 2006. "Addressing the paediatric HIV epidemic: a perspective from the Western
Cape Region of South Africa." Trans R Soc Trop Med Hyg, 100(1):19-23.
In the Western Cape province of South Africa, a prevention of mother-to-child-transmission (PMTCT)
intervention programme, based on short-course nevirapine, achieved universal coverage in 2003. Despite
this programme, an estimated 1,400-1,650 HIV-infected children were born in the province in that year.
These crude estimates suggest that there are many children in the province who need medical care. Several
strategies could collectively reduce the size of the paediatric epidemic and improve the outcome of HIVinfected children in the region, including intensification of the existing PMTCT programme and provision of
antiretroviral therapy (ART) for children with moderate or severe disease. Progress towards implementing
these interventions is discussed. Future challenges include understanding the factors that favour long-term
survival of children on highly active antiretroviral therapy in resource-limited settings, identifying appropriate
treatment for the metabolic complications of ART, and the provision of adolescent services for long-term
survivors. Developments over the next few years will determine whether these challenges can be met.
Eshleman, S. H., D. R. Hoover, S. E. Hudelson, S. Chen, S. A. Fiscus, E. PiwowarManning, J. B. Jackson, N. I. Kumwenda, and T. E. Taha. 2006. "Development of
nevirapine resistance in infants is reduced by use of infant-only single-dose
nevirapine plus zidovudine postexposure prophylaxis for the prevention of
mother-to-child transmission of HIV-1." J Infect Dis, 193(4):479-81.
We analyzed the development of nevirapine (NVP) resistance in human immunodeficiency virus type 1 (HIV1)-infected Malawian infants who received regimens containing single-dose NVP (SD-NVP) for the
prevention of mother-to-child transmission (MTCT) of HIV-1. All infants received SD-NVP, and some
randomly received zidovudine (ZDV) as well. Mothers did or did not receive SD-NVP on the basis of when
they arrived at the hospital for delivery. In infants 6-8 weeks of age, NVP resistance was less frequent when
infants had received SD-NVP plus ZDV and mothers had not received SD-NVP than when infants had
received SD-NVP alone and mothers had received SD-NVP (4/15 [27%] vs. 20/23 [87%]; P < .001). The risk
of MTCT of HIV-1 was comparable with these regimens. Infant-only prophylaxis also eliminates the
development of NVP resistance in mothers.
Loubser, S., P. Balfe, G. Sherman, S. Hammer, L. Kuhn, and L. Morris. 2006. "Decay of
K103N mutants in cellular DNA and plasma RNA after single-dose nevirapine to
reduce mother-to-child HIV transmission." Aids, 20(7):995-1002.
OBJECTIVES:: Single-dose nevirapine (sd-NVP) for prevention of mother-to-child HIV-1 transmission is
associated with selection of resistant viral variants, particularly the Lysine (K) to Asparagine (N) mutation at
codon 103 (K103N) of reverse transcriptase. As this may influence subsequent treatment responses, a
better understanding of the dynamics of decay and persistence of this variant is needed. DESIGN AND
METHODS:: We measured the frequency of K103N mutants among a cohort of HIV-1-infected pregnant
women recruited at an out-patient clinic in Johannesburg, South Africa. Samples taken 6 weeks, 3, 7 and 12
months after delivery from 67 HIV-1-infected women who received sd-NVP during labor to prevent
transmission were analyzed. Quantification of K103N mutants in maternal plasma viral RNA and cellular
DNA was done using an allele-specific real-time polymerase chain reaction assay capable of detecting
codons AAC and AAT if their frequency was > 0.002 of the total viral population. RESULTS:: Using the
allele-specific assay, 87.1% (27/31) of RNA samples and 52.3% (23/44) of DNA samples collected 6 weeks
after sd-NVP had detectable K103N variants. This declined to 65.4% (17/26), 38.9% (14/36), and 11.3%
(6/53) in RNA at 3, 7 and 12 months respectively, and to 4.2% (2/48) in DNA at 12 months.
CONCLUSIONS:: K103N resistant variants were present in almost all women at 6 weeks post-sd-NVP but
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declined rapidly over time. Resistant variants were detected less frequently in cellular DNA with persistence
in this compartment by 12 months post-sd-NVP among only a minority.
Malyuta, R., M. L. Newell, M. Ostergren, C. Thorne, and N. Zhilka. 2006. "Prevention of
mother-to-child transmission of HIV infection: Ukraine experience to date." Eur J
Public Health, 16(2):123-7.
BACKGROUND: Despite the availability of effective interventions for the prevention of mother-to-child
transmission (PMTCT), questions remain regarding implementation of programmes in settings with limited
resources. This article sets out to describe the first 2 years of the implementation of the national PMTCT
programme in Ukraine. METHODS: National data sources and data from a cohort of pregnant HIV-infected
women delivering in 13 centres in Ukraine since 2000 were analysed. RESULTS: Interventions for
prevention of MTCT have been implemented as a national programme within Ukraine's well developed
infrastructure for maternal and child health. Implementation of an 'opt-out' model of counselling and HIV
testing in antenatal clinics resulted in a 97% uptake of women who agreed to be HIV tested. In 2002,
approximately 91% of HIV-positive pregnant women received ARV prophylaxis (mainly single-dose
nevirapine or short-course zidovudine) for PMTCT. The MTCT rate has decreased from 30% in 2000 to 10%
in 2002. The need to scale-up prevention interventions in pregnant women with risky behaviour and late
access to medical services was identified in a review of the national programme in 2003. CONCLUSIONS:
Further implementation of a comprehensive approach for the prevention of HIV infection in infants, including
more extensive ART regimen, as recommended by WHO, would help Ukraine to achieve the strategic goal
of virtual elimination of HIV infection in infants by 2010.
McIntyre, J. 2006. "Strategies to prevent mother-to-child transmission of HIV." Curr Opin
Infect Dis, 19(1):33-8.
PURPOSE OF REVIEW: This review describes recent advances in the prevention of mother-to-child
transmission, focusing on the use of antiretroviral treatment strategies in pregnancy, and discusses the
emergence of viral resistance following the use of nevirapine to prevent mother-to-child transmission.
RECENT FINDINGS: Mother-to-child transmission has been dramatically reduced in developed countries by
the use of antiretroviral treatment and avoidance of breastfeeding. Highly active antiretroviral therapy use in
pregnancy is recommended for women who require ongoing treatment, and, where available, is also very
effective in reducing mother-to-child transmission in women with higher CD4 counts. The addition of a
maternal and infant nevirapine dose to antenatal zidovudine can reduce transmission to below 5%,
approximately half the transmission rate that can be achieved by single-dose nevirapine alone. The
emergence of resistant virus following nevirapine use is a concern, occurring in up to 60% of mothers and
50% of infants following a single dose. Addition of zidovudine and lamivudine for 4-7 days postpartum can
reduce the risk of resistance to 10%. SUMMARY: There is broad consensus on an approach to preventing
mother-to-child transmission, which provides antiretroviral treatment in pregnancy and beyond to those
women who need it, and an effective prophylactic regimen for those who do not yet need treatment, These
regimens include highly active antiretroviral therapy, where available, a zidovudine-plus-nevirapine regimen
in other settings, or nevirapine alone where this is all that is possible. More work is needed on the impact of
nevirapine resistance and on reducing breast-milk transmission.
McIntyre, J. A. 2006. "Controversies in the use of nevirapine for prevention of mother-tochild transmission of HIV." Expert Opin Pharmacother, 7(6):677-85.
The use of nevirapine to prevent mother-to-child transmission of HIV has been controversial. Claims of high
rates of toxicity have not been confirmed in clinical trials or extensive programme experience of use of the
regimen. Whilst single-dose nevirapine can reduce transmission rates to approximately 10-15%, this can be
halved by the addition of single-dose nevirapine to short-course regimens of zidovudine. The selection of
resistant virus is reported in 20-50% of mothers and 50% of infants following one dose of nevirapine,
although the impact of this on future treatment options is not fully understood. An increased risk of severe
hepatotoxicity has been reported with long-term nevirapine-containing triple-therapy treatment regimens in
women with CD4+ counts > 250 cells/mm3.
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Palmer, S., V. Boltz, N. Martinson, F. Maldarelli, G. Gray, J. McIntyre, J. Mellors, L.
Morris, and J. Coffin. 2006. "Persistence of nevirapine-resistant HIV-1 in women
after single-dose nevirapine therapy for prevention of maternal-to-fetal HIV-1
transmission." Proc Natl Acad Sci U S A.
Single-dose nevirapine (sdNVP) for prevention of mother-to-child transmission of HIV-1 can select
nevirapine (NVP)-resistant variants, but the frequency, duration, and clinical significance of this resistance is
not well defined. We used a sensitive allele-specific PCR assay to assess the emergence and persistence of
NVP-resistant variants in plasma samples from 22 women with HIV-1 subtype C infection who participated in
a study of sdNVP for prevention of mother-to-child transmission of HIV-1. The women were categorized into
three groups on the basis of detection of NVP resistance by standard genotype analysis. Group 1 (n = 6)
had NVP resistance detected at 2 and 6 mo after sdNVP, but not at 12 mo. Group 2 (n = 9) had NVP
resistance detected at 2 mo, but not 6 mo. Group 3 (n = 7) had no NVP resistance detected at any time
point. Allele-specific PCR analysis for the two most common NVP resistance mutations (K103N and Y181C)
detected NVP-resistant variants in most (16 of 21) samples that were negative for NVP resistance by
standard genotype, at levels ranging from 0.1% to 20% 1 yr after treatment. The frequency of NVP-resistant
mutations decreased over time, but persisted above predose levels for more than 1 yr in >/=23% of the
women. These findings highlight the urgent need for studies assessing the impact of sdNVP on the efficacy
of subsequent antiretroviral therapy containing NVP or other nonnucleoside reverse transcriptase inhibitors.
Reynolds, H. W., B. Janowitz, R. Homan, and L. Johnson. 2006. "The Value of
Contraception to Prevent Perinatal HIV Transmission." Sex Transm Dis, Publish
Ahead of Print.
OBJECTIVE:: The objective of this study was to highlight the value of preventing unintended pregnancies
among HIV-infected women as a strategy to prevent perinatal HIV transmission. GOAL:: The goal of this
study was to assess the cost-effectiveness of family planning programs to avert HIV-positive births with the
current programmatic emphasis: prenatal care services that provide and promote nevirapine for prevention
of mother-to-child transmission of HIV. STUDY DESIGN:: Cost-effectiveness analyses were conducted from
the health system perspective during 1 year with a hypothetical sub-Saharan African population. Expected
program costs were combined with number of HIV-positive births averted for each strategy. RESULTS:: At
the same level of expenditure, the contraceptive strategy averts 28.6% more HIV-positive births than
nevirapine for prevention of mother-to-child transmission of HIV. CONCLUSIONS:: Increasing contraceptive
use among nonusers of contraception who do not want to get pregnant is cost-effective and is an equally
important strategy to prevent perinatal transmission as prenatal care programs that provide and promote
nevirapine to HIV-infected mothers.
Schmitz, T., N. Kleinkauf, B. Klempa, H. Ringe, V. Varnholt, and I. Grosch-Worner.
2006. "Transmission of human immunodeficiency virus type 1 nevirapine
resistance mutation K103N from a treatment-naive mother to her child." Pediatr
Infect Dis J, 25(3):275-6.
Vertical infection of drug-resistant human immunodeficiency virus type 1 (HIV-1) has occasionally been
reported in children from pretreated mothers with HIV-1 infection. In this report, a treatment-naive mother
transmitted HIV-1 resistance mutation K103N against nevirapine to her child.
Simpore, J., V. Pietra, A. Savadogo, S. Pignatelli, J. B. Nikiema, W. M. Nadembega, J.
Yara, N. Zoungrana, D. Bakouan, V. Colizzi, F. Castelli, and S. Musumeci. 2006.
"Reduction of mother-to-child transmission of HIV at Saint Camille Medical
Centre in Burkina Faso." J Med Virol, 78(2):148-52.
One thousand three hundred and twenty-eight pregnant women with less than 32 weeks of amenorrhea
received voluntary counseling and testing at Saint Camille Medical Center from May 1, 2002 to December
30, 2004. Following informed consent and pre-test counseling, HIV screening was performed in 1,202
women. According to the prevention protocol, HIV-positive women received a single dose of Nevirapine (200
Page 4 of 56
mg) during their labor, while their newborn received a single dose of Nevirapine (2 mg/kg) within 72 hr from
birth. HIV seroprevalence (11.2%) was higher than in the overall population. One hundred and ninety-three
children were born at the end of December 2004; 53 children (27.5%) followed a short breastfeeding
protocol for 4 months, while 140 (72.5%) were fed artificially. All the children underwent RT-PCR test for HIV
5-6 months after their birth: 173 (89.6%) were HIV negative whilst 20 children (10.4%) were HIV positive.
Out of the 20 positive children 5/53 (9.4%) had received breast milk for 4 months, while the remaining
15/140 (10.7%) had been fed artificially (P = 0.814). Artificially fed babies (3/140 (2.1%)) and 1/53 (1.9%) of
those breast fed for 4 months deceased according to mortality rate of HIV-positive children. This shows that
there is no statistically significant difference (P = 0.648) between the mortality of artificially fed (3/140 or
2.1%) and breast-fed (1/53 or 1.9%) children. Artificially fed children (20/140 (14.3%)) and 5/53 (9.4%) of
breast-fed children died within 6-10 months. This figure indicates that there is no significant difference
between the mortality rate of artificially and that of breast-fed children (P = 0.427). Although the HIV
prevention program reduced significantly the vertical transmission of HIV at Saint Camille Medical Center,
the mortality of artificially fed children was still high due to gastrointestinal diseases. The HIV diagnosis by
RT-PCR technique was of great help in the early identification of HIV-infected children.
Smith, D. M. 2006. "The controversies of nevirapine for preventing mother-to-child HIV
transmission." Aids, 20(2):281-3.
Soorapanth, S., S. Sansom, M. Bulterys, M. Besser, G. Theron, and M. G. Fowler.
2006. "Cost-effectiveness of HIV Rescreening During Late Pregnancy to Prevent
Mother-to-child HIV Transmission in South Africa and Other Resource-limited
Settings." J Acquir Immune Defic Syndr.
SUMMARY:: A decision analysis model, from a health care system perspective, was used to assess the
cost-effectiveness of HIV rescreening during late pregnancy to prevent perinatal HIV transmission in South
Africa, a country with high HIV prevalence and incidence among pregnant women. Because new HIV
prenatal prophylactic and pediatric antiretroviral therapy (ART) regimens are becoming more widely
available, the study was carried out with different combinations of the two. With an estimated HIV incidence
during pregnancy of 2.3 per 100 person-years, HIV rescreening would prevent additional infant infections
and result in net savings when zidovudine plus single-dose nevirapine or single-dose nevirapine is used for
perinatal HIV prevention, and ART was available to treat perinatally HIV-infected children. The cost savings
were robust over a wide range of parameter values when ART was available to treat perinatally HIV-infected
children but were more sensitive to variations around the baseline when ART was not available. The
minimum time interval between the initial and repeat screens would be from 3 to 18 weeks, depending on
prophylactic and treatment regimens, for HIV rescreening to be cost saving. Overall, HIV rescreening late in
pregnancy in high-prevalence, resource-limited settings such as South Africa would be a cost-effective
strategy for reducing mother-to-child transmission.
Capparelli, E., N. Rakhmanina, and M. Mirochnick. 2005. "Pharmacotherapy of perinatal
HIV." Semin Fetal Neonatal Med, 10(2):161-75.
Continued spread of HIV infection among women has led to the use of antiretrovirals in pregnant women
and their newborns. Regional strategies to prevent mother-to-child transmission are evolving. Altered drug
disposition during pregnancy may require altered dosing or 'boosted' therapies to avoid treatment failure.
Maturing drug elimination pathways in newborns must also be considered for effective therapy. Potential
teratogenic effects and increased sensitivity to antiretroviral toxicities might be encountered in this
population. Use of highly active antiretroviral therapy (HAART) to suppress viral replication combined with
formula feeding can reduce the rate of mother-to-child HIV transmission to less than 2%. In resource-limited
settings, less intensive regimens including zidovudine, lamivudine and nevirapine still substantially reduce
mother-to-child transmission. Although difficult to perform, clinical trials to determine the safety,
pharmacokinetics and optimal dosing of antiretroviral in pregnant women and their newborns are urgently
needed.
Chersich, M. F. and G. E. Gray. 2005. "Progress and Emerging Challenges in
Preventing Mother-to-Child Transmission." Curr Infect Dis Rep, 7(5):393-400.
Page 5 of 56
There is a widening gulf between the effectiveness of interventions for preventing mother-to-child
transmission (PMTCT) of HIV in sub-Saharan Africa and other regions of the world. Compared with longcourse, triple antiretroviral regimens used in Brazil, Europe, and the United States, most countries in subSaharan Africa use a less effective regimen consisting of single-dose nevirapine (NVP). Furthermore, the
documentation of unacceptable levels of resistance following this regimen makes it prudent to review current
PMTCT strategies. Not only is it necessary to review the use of single-dose NVP for PMTCT, but efforts to
minimize breast milk transmission of HIV should be enhanced. This review summarizes the programmatic
and evidence-based reasons for adopting a standardized approach to long-course, triple-drug MTCT
prophylaxis in sub-Saharan Africa. Antiretroviral treatment programs in resource-constrained settings have
achieved similar levels of effectiveness as high-income countries, despite adopting standardized
approaches to antiretroviral treatment. Similarly, in resource-constrained settings with adequate
infrastructure and programmatic capacity, use of standardized, long-course, triple-drug regimens for MTCT
prevention are likely to achieve levels of effectiveness seen in Brazil, Europe, and the United States.
Chi, B. H., L. Wang, J. S. Read, M. Sheriff, S. Fiscus, E. R. Brown, T. E. Taha, M.
Valentine, and R. Goldenberg. 2005. "Timing of maternal and neonatal dosing of
nevirapine and the risk of mother-to-child transmission of HIV-1: HIVNET 024."
Aids, 19(16):1857-64.
OBJECTIVE: Despite a growing emphasis worldwide on complex and potent antiretroviral drug regimens for
the prevention of mother-to-child transmission of HIV-1 (MTCT), two-dose nevirapine (NVP) prophylaxis
remains an important choice in many settings. We analyzed data from a multicenter clinical trial to determine
whether timing of maternal or infant NVP was associated with MTCT between delivery and 6 weeks of age
(intrapartum/early postnatal transmission; I/EP). METHODS: HIVNET 024 was a placebo-controlled, doubleblind trial of empiric antibiotics to reduce chorioamnionitis-associated MTCT. This secondary analysis used
data collected in the original randomized trial. Enrolled women were instructed to self-administer NVP at
labor onset; infants were to receive a dose within 72 h of birth. RESULTS: Data regarding 1491 motherinfant pairs were analyzed. The overall I/EP HIV-1 transmission rate was 8.1% at 6 weeks. Almost all
women (93%) ingested NVP within 24 h of delivery; 90% of infants were given NVP within 48 h after
delivery. Variations in mother or infant dose timing did not influence transmission rates, even when the
combined pattern of both was taken into account through multivariate analysis. In the subset of women
ingesting NVP <or= 2 h before delivery, early NVP administration to the infant (< 4 h after birth) was not
associated with lower MTCT risk when compared with later administration (>or= 4 h). CONCLUSION:
Variations in the timing of maternal and infant NVP doses (within reasonable proximity to delivery) do not
appear to affect the risk of MTCT.
Chopra, M., T. Doherty, D. Jackson, and A. Ashworth. 2005. "Preventing HIV
transmission to children: quality of counselling of mothers in South Africa." Acta
Paediatr, 94(3):357-63.
AIM: To assess the quality of counselling provided to mothers through the programme to prevent mother-tochild transmission (PMTCT) of HIV in South Africa. METHODS: Structured observations of consultations
and exit interviews with 60 mothers attending clinics at three purposively selected PMTCT sites across
South Africa were conducted. RESULTS: Twenty-two counsellors were observed. The general quality of
communication skills was very good, and 73% of HIV-negative mothers were informed of the advantages of
exclusive breastfeeding (EBF). However, only one of 34 HIV-positive mothers was informed about the
possible side effects of nevirapine, and none was told what to do when it occurred. Only two HIV-positive
mothers were asked about essential conditions for safe formula feeding before a decision about an infant
feeding option was made. None of the 12 mothers choosing to breastfeed was shown how to position the
baby correctly on the breast or asked whether they thought EBF was feasible. Fewer than a quarter of
mothers expressed confidence in performing the actions required, and 85% could not define the term EBF.
CONCLUSION: The poor quality of counselling in the PMTCT programme will reduce the effectiveness of
these programmes. As they are being scaled up, there needs to be far more attention paid towards the
counselling of mothers, especially with regards to optimal infant feeding.
Page 6 of 56
Coetzee, D., K. Hilderbrand, A. Boulle, B. Draper, F. Abdullah, and E. Goemaere. 2005.
"Effectiveness of the first district-wide programme for the prevention of mother-tochild transmission of HIV in South Africa." Bull World Health Organ, 83(7):48994.
OBJECTIVE: The aim of this study was to estimate the field efficacy of the first routine programme for the
prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) initiated in
South Africa, in the subdistrict of Khayelitsha. METHODS: A consecutive sample of 658 mother-infant pairs,
identified from the PMTCT register from 1 March to 30 November 2003, were identified for enrolment in this
study. Details of the regimen received were established and HIV status of the infants at between 6 and 10
weeks of age was determined by qualitative DNA polymerase chain reaction. Zidovudine (AZT) was
provided antenatally from week 34 of gestation and during labour. Infant formula milk was-offered to mothers
who chose not to breastfeed. The protocol was amended in July 2003 such that women who had received <
2 weeks of treatment with AZT were given a single dose of nevirapine (NVP) at the onset of labour, and the
infant received a weight-adjusted dose of NVP within 72 h of delivery. RESULTS: Of the 535 mother-infant
pairs (81%) eventually included in the study, 410 (77%) received an effective PMTCT intervention according
to the protocol. The rate of transmission of HIV from mother to child was 8.8% (95% confidence interval (CI),
6.2-10.9). A maternal age of > 25 years was the only significant independent risk factor for transmission
(odds ratio, 2.12; 95% CI, 1.14-4.07). CONCLUSION: The results of this study demonstrate the feasibility
and effectiveness of a large-scale PMTCT programme in an urban public-sector setting.
Cressey, T. R., G. Jourdain, M. J. Lallemant, S. Kunkeaw, J. B. Jackson, P. Musoke, E.
Capparelli, and M. Mirochnick. 2005. "Persistence of nevirapine exposure during
the postpartum period after intrapartum single-dose nevirapine in addition to
zidovudine prophylaxis for the prevention of mother-to-child transmission of HIV1." J Acquir Immune Defic Syndr, 38(3):283-8.
OBJECTIVE: To determine nevirapine (NVP) plasma levels during the postpartum period after a single
intrapartum NVP dose for the prevention of mother-to-child transmission. METHODS: Plasma samples at
delivery and during days 8 to 45 postpartum were obtained from HIV-infected Thai women who received an
intrapartum NVP dose in the Perinatal HIV Prevention Clinical Trial-2 (PHPT-2) for the prevention of
perinatal HIV transmission. These data were combined with NVP concentration data from 2 phase 1 studies
of NVP for a population analysis. RESULTS: The median NVP level fell to 68 ng/mL (range: <50-228, n =
43) 8 to 14 days after dosing and to 51 ng/mL (range: <50-166, n = 25) between 15 and 21 days. During the
second and third weeks postpartum, NVP levels were below the limit of quantitation in 23% and 44% of
samples, respectively. Between 21 and 45 days, no sample had a quantifiable NVP concentration. A
simulation derived from the population analysis predicts that NVP concentration falls to less than 10 ng/mL
in 5% of women by 11 days, in 50% of women by 17.5 days, and in 95% of women by 28 days.
CONCLUSIONS: Significant NVP concentrations remained for up to 20 days in these Thai women. To
ensure that coverage is maintained until NVP concentrations fall to nonsuppressive levels, 1 month of
additional antiretroviral treatment after delivery should be considered to prevent the emergence of resistant
viruses.
Dabis, F., L. Bequet, D. K. Ekouevi, I. Viho, F. Rouet, A. Horo, C. Sakarovitch, R.
Becquet, P. Fassinou, L. Dequae-Merchadou, C. Welffens-Ekra, C. Rouzioux,
and V. Leroy. 2005. "Field efficacy of zidovudine, lamivudine and single-dose
nevirapine to prevent peripartum HIV transmission." Aids, 19(3):309-18.
OBJECTIVES: In Africa, single-dose nevirapine (NVPsd), short regimens of zidovudine (ZDV) or ZDV +
lamivudine (3TC) are recommended to prevent peripartum mother-to-child HIV transmission (PMTCT). We
evaluated the 6-week field efficacy of two more PMTCT drug combinations. DESIGN: An open-label
intervention cohort in Abidjan. METHODS: In 2001-2002, consenting women started oral ZDV 300 mg twice
daily (bid) at > or =36 weeks of gestation, with 600 mg of ZDV + 200 mg NVPsd orally at beginning of
labour. In 2002-2003, the antepartum regimen at > or =32 weeks comprised ZDV as previously + 3TC 150
mg bid; the labour dose comprised ZDV + NVPsd as previously + 300 mg 3TC orally. Neonates received
ZDV syrup (2 mg/kg per 6 h) for 7 days + NVPsd syrup (2 mg/kg) on day 2 in both periods. Each woman
Page 7 of 56
was assisted to either use breast milk substitutes or breastfeed exclusively. Paediatric HIV infection was
diagnosed by plasma HIV RNA viral load at 4 weeks, confirmed at 6 weeks. The reference group was a
cohort receiving a short regimen of ZDV > or = 36-38 weeks in 1995-2000 in the same population.
RESULTS: A total of 1144 HIV-infected pregnant women were included: 351 with ZDV, 420 with ZDV +
NVPsd and 373 with ZDV + 3TC + NVPsd; 1010 livebirths were eligible for analysis; 79 children were HIVinfected peripartum. Six-week transmission probability was 6.5% [95% confidence interval (CI), 3.9-9.1%)
with ZDV + NVPsd, a 72% reduction compared with ZDV alone (95% CI, 52-88%; P = 0.0002 adjusted on
maternal CD4, clinical stage and breastfeeding). It was 4.7% (95% CI, 2.4-7.0%) with ZDV + 3TC + NVPsd
(P = 0.34 compared with ZDV + NVPsd). CONCLUSIONS: A short-course of ZDV + NVPsd prevents most
peripartum HIV transmission in Africa. This regimen could be added to international guidelines.
Doherty, T. M., D. McCoy, and S. Donohue. 2005. "Health system constraints to optimal
coverage of the prevention of mother-to-child HIV transmission programme in
South Africa: lessons from the implementation of the national pilot programme."
Afr Health Sci, 5(3):213-8.
Background: It is three years since the government of South Africa began implementing a PMTCT
programme. Over this period of time attempts have been made to scale up this programme across all
provinces under routine health service conditions. Objectives: To report on the uptake and performance of
South Africa's national pilot programme for preventing mother to child HIV transmission (PMTCT) and to
identify health system constraints to optimal coverage. Methods: Routine programme data were collected
from antenatal records and delivery registers at the pilot sites and interviews were conducted with health
workers on site and with provincial programme managers. Results: Routine PMTCT programme data were
collected from all 18 pilot sites for the period January to December 2002. During this period, of 84406
women attending the sites for first antenatal visits, 47267 (56%) agreed to an HIV test. 14340 (30%) of the
women tested were HIV positive and of these 7853 (55%) were dispensed nevirapine. 7950 (99%) of infants
born to women identified as being HIV positive received nevirapine syrup. 58% (4196/7237) of HIV positive
women expressed an intention to exclusively formula feed, and 42% (3041/7237) intended to exclusively
breastfeed. 1907 infants were due for 12 month HIV testing between January and December 2002, of these
949 (50%) infants were tested. Conclusion: Programme effectiveness was limited by the low rate of HIV test
acceptance, poor delivery of nevirapine to mothers and inability to track mother-infant pairs postnatally for
12-month HIV testing of infants. Infant feeding intentions of mothers suggest inadequate counselling and
possible negative effects of the provision of free formula milk. The poor perfor-mance of the main
components of this programme will seriously reduce its operational effectiveness. There is a need for
greater integration of VCT within antenatal care, a review of the current policy of providing free formula milk
and an alternative model for mother-infant follow up.
Ekouevi, D. K., B. Tonwe-Gold, and F. Dabis. 2005. "Advances in the prevention of
mother-to-child transmission of HIV-1 infection in resource-limited settings." AIDS
Read, 15(9):479-80, 487-93.
Ten years after the first trials demonstrating the efficacy of zidovudine (ZDV) for the prevention of mother-tochild transmission (pMTCT) of HIV, different antiretroviral approaches have been validated in resourcelimited settings. Remarkable progress has been made in the last 4 years, with trials demonstrating the
efficacy of postexposure antiretroviral prophylaxis in Malawi, as well as studies in Thailand and Cote d'Ivoire
assessing the efficacy and viral resistance patterns of short-course regimens combining ZDV plus singledose nevirapine (sdNVP). The field efficacy of a short course of ZDV plus lamivudine (3TC), together with
sdNVP, has also been recently reported, with 6-week transmission rates below 5% for the first time in Africa
in a population in which 40% breast-feed. The introduction of HAART for pregnant women has begun on a
small scale in resource-limited settings and will hopefully further reduce transmission. What remains is the
crucial issue of viral resistance after antiretroviral therapy for pMTCT, especially in the context of the
growing availability and use of sdNVP in national pMTCT programs. Preliminary data from South Africa and
Cote d'Ivoire suggest that the maternal use of ZDV plus 3TC for at least 3 days postpartum may reduce the
occurrence of resistance mutations after maternal exposure to sdNVP. In the context of increasing
controversy surrounding the use of sdNVP for pMTCT, the World Health Organization has recently reiterate
its recommendations for its use for pMTCT in resource-constrained settings within a wide panel of
antiretroviral regimens, in order to allow greater and quicker population coverage. The field application of
pMTCT study results is a real challenge, and innovative approaches need to be designed an evaluated ot
Page 8 of 56
increase uptake of pMTCT programs in resource-poor settings. Research must continue to identify new
interventions and new antiretroviral drugs for pMTCT.
Eshleman, S. H., L. A. Guay, A. Mwatha, E. Brown, P. Musoke, F. Mmiro, and J. B.
Jackson. 2005. "Comparison of mother-to-child transmission rates in Ugandan
women with subtype A versus D HIV-1 who received single-dose nevirapine
prophylaxis: HIV Network For Prevention Trials 012." J Acquir Immune Defic
Syndr, 39(5):593-7.
OBJECTIVE: To compare the rate of mother-to-child transmission (MTCT) in women with subtype A versus
D HIV-1 who received single-dose nevirapine (NVP). METHODS: The MTCT rates were compared in
women with subtype A versus D at birth and at 8 weeks and 18 months of age of the infants. The rate of late
MTCT (after 8 weeks of age) was also analyzed. RESULTS: HIV-1 subtypes were determined for 300 of 306
women who received NVP in the HIV Network for Prevention Trials 012 study (158 women with subtype A
and 105 women with subtype D). Infant infection status was known for 297 women. The cumulative rate of
MTCT at 18 months was 13.2% for subtype A and 18.3% for subtype D (P=0.34). The rate of late
transmission was 3.8% for subtype A and 7.6% for subtype D (P=0.28). Maternal baseline viral load was a
significant predictor of MTCT, but maternal baseline CD4 cell count and subtype were not. CONCLUSIONS:
No significant difference was observed in the rate of MTCT in women with subtype A versus D. There was a
trend toward a higher rate of MTCT among women with subtype D, however, which was also apparent
among women whose infants were infected after 8 weeks of age.
Eshleman, S. H., L. A. Guay, J. Wang, A. Mwatha, E. R. Brown, P. Musoke, F. Mmiro,
and J. B. Jackson. 2005. "Distinct patterns of emergence and fading of K103N
and Y181C in women with subtype A vs. D after single-dose nevirapine: HIVNET
012." J Acquir Immune Defic Syndr, 40(1):24-9.
BACKGROUND: The HIVNET 012 trial in Uganda demonstrated that single-dose nevirapine (NVP) can
prevent HIV-1 mother-to-child transmission. NVP resistance (NVPR) mutations were detected in 25% of
women 6 to 8 weeks after NVP, with a higher rate of NVPR in women with subtype D than A. This study
examined emergence and fading of specific NVPR mutations in women with these subtypes. METHODS:
Plasma HIV-1 was analyzed with the ViroSeq genotyping system (Celera Diagnostics, Alameda, CA).
Genotypes were obtained from paired samples collected 7 days and 6 to 8 weeks after NVP from 140
women, 83 with subtype A and 57 with subtype D. RESULTS: The rate of NVPR was similar in women with
subtype A vs. D at 7 days but was higher in subtype D than A at 6 to 8 weeks. The higher rate of NVPR in
subtype D was explained by at least 2 factors: Y181C faded from detection at a greater rate in women with
subtype A (odds ratio = 3.06; 95% CI, 1.04, 8.90) and K103N accumulated at a greater rate in women with
subtype D (odds ratio = 1.74; 95% CI, 0.62, 4.87). CONCLUSIONS: HIV-1 subtype influences selection and
fading of HIV-1 variants with specific drug resistance mutations after antiretroviral drug exposure.
Eshleman, S. H., D. R. Hoover, S. Chen, S. E. Hudelson, L. A. Guay, A. Mwatha, S. A.
Fiscus, F. Mmiro, P. Musoke, J. B. Jackson, N. Kumwenda, and T. Taha. 2005.
"Resistance after single-dose nevirapine prophylaxis emerges in a high
proportion of Malawian newborns." Aids, 19(18):2167-9.
The administration of single-dose nevirapine to women in labor and their infants can prevent HIV-1 motherto-child transmission. We examined nevirapine resistance in infants who were HIV-1 infected despite singledose nevirapine prophylaxis, including 18 Ugandan infants (HIVNET 012 trial, nine subtype A and nine
subtype D) and 23 Malawian infants (NVAZ trial, all subtype C). Nevirapine resistance was more frequent in
infants with subtype C than with subtypes A and D (87 versus 50%, P = 0.016).
Gray, G. E., M. Urban, M. F. Chersich, C. Bolton, R. van Niekerk, A. Violari, W.
Stevens, and J. A. McIntyre. 2005. "A randomized trial of two postexposure
Page 9 of 56
prophylaxis regimens to reduce mother-to-child HIV-1 transmission in infants of
untreated mothers." Aids, 19(12):1289-97.
BACKGROUND: Single-dose nevirapine (NVP) prophylaxis to mother and infant is widely used in resourceconstrained settings for preventing mother-to-child transmission (MTCT) of HIV-1. Where women do not
access antenatal care or HIV testing, postexposure prophylaxis to the infant may be an important
preventative strategy. METHODS: This multicentre, randomized, open-label clinical trial (October 2000 to
September 2002) in South Africa compared single-dose NVP with 6 weeks of zidovudine (ZDV),
commenced within 24 h of delivery among 1051 infants whose mothers had no prior antiretroviral therapy.
HIV-1 infection rates were ascertained at birth, and at 6 and 12 weeks of age. Kaplan-Meier survival
methods were used to estimate HIV-1 infection rates in an intention-to-treat analysis. RESULTS: Overall, 6
week and 12 week MTCT probability was 12.8% [95% confidence interval (CI),10.5-15.0] and 16.3% (95%
CI,13.4-19.2), respectively. At 12 weeks, among infants who were not infected at birth, 24 (7.9%) infections
occurred in the NVP arm and 41 (13.1%) in the ZDV arm (log rank P = 0.06). Using multivariate analysis,
factors associated with infection following birth were ZDV use [odds ratio (OR), 1.8; 95% CI,1.1-3.2; P =
0.032), maternal CD4 cell count < 500 x 10(6) cells/l (OR, 2.5; 95% CI,1.3-5.0; P = 0.007), maternal viral
load > 50 000 copies/ml (OR, 3.6; 95% CI,2.0-6.2; P < 0.0001) and breastfeeding (OR, 2.2; 95% CI,1.3-3.8;
P = 0.006). CONCLUSION: A single-dose of NVP given to infants offers protection against HIV-1 infection
and should be a strategy used in infants of mothers with untreated HIV infection.
Hudson, C. P. 2005. "Zidovudine monotherapy and the prevention of mother-to-child
HIV-1 transmission." Lancet Infect Dis, 5(2):68.
James, J. S. 2005. "IOM: nevirapine study is reliable." AIDS Treat News, (411):6.
The Institute of Medicine re-analyzed the key study that first showed prevention of mother-to-child HIV
transmission by single-dose nevirapine. The IOM released a 150-page report concluding that the study was
properly conducted and its results are valid.
Jones, D., N. Parkin, S. E. Hudelson, L. A. Guay, P. Musoke, F. Mmiro, J. B. Jackson,
and S. H. Eshleman. 2005. "Genetic linkage of nevirapine resistance mutations in
HIV type 1 seven days after single-dose nevirapine." AIDS Res Hum
Retroviruses, 21(4):319-24.
The HIVNET 012 trial in Uganda demonstrated that a regimen of single-dose nevirapine (NVP) can prevent
HIV-1 mother-to-child transmission. Previous studies show that HIV-1 with one or more NVP resistance
(NVPR) mutations can be selected in many women as early as 7 days after single-dose NVP. We evaluated
the genetic linkage of NVPR mutations in plasma from women in HIVNET 012 collected 7 days after singledose NVP administration. The HIV-1 pol region was amplified and cloned from 20 plasma samples (16 with
NVPR mutations detected by population sequencing and 4 with no NVPR mutations detected), and 10
clones from each sample were sequenced. Up to five different NVPR mutations were detected in clones
from a single sample. K103N and Y181C were the most common mutations detected. Clones with two
genetically linked mutations were detected in four samples. Different combinations of NVPR mutations were
linked in individual clones, but none of the clones contained both K103N and Y181C. Further studies are
needed to evaluate whether selection of minority variants with one or more NVPR mutations after singledose NVP is clinically relevant.
Kagaayi, J., M. L. Dreyfuss, G. Kigozi, M. Z. Chen, F. Wabwire-Mangen, D. Serwadda,
M. J. Wawer, N. K. Sewankambo, F. Nalugoda, N. Kiwanuka, M. Kiddugavu, and
R. H. Gray. 2005. "Maternal self-medication and provision of nevirapine to
newborns by women in Rakai, Uganda." J Acquir Immune Defic Syndr,
39(1):121-4.
Page 10 of 56
To assess the effectiveness of maternal self-administration of nevirapine for prevention of mother-to-child
transmission (MTCT) of HIV, we conducted a program to provide maternal and newborn doses of nevirapine
to pregnant women in rural Uganda. Women provided blood for HIV testing and were offered voluntary
counseling and testing (VCT) during annual community HIV surveys. HIV-positive women who accepted
VCT were offered nevirapine tablets and syrup. Blood samples were collected postpartum from women and
their babies. Infants were tested for HIV by polymerase chain reaction (PCR), and a subsample of maternal
and infant blood was assayed for nevirapine. Among the 981 women tested for HIV, 900 (91.7%) accepted
VCT, of whom 105 (11.7%) were HIV-positive. Ninety-three women accepted nevirapine, of whom 81
(87.1%) were followed postpartum; 75 (92.6%) reported receipt of the drug, and 69 reported taking the
tablets (85.2%). There were 81 liveborn babies (3 sets of twins), and 67 (84.8%) received the syrup. In a
subsample of 25 mothers reporting receipt of the drug, nevirapine was detected in 22 (88.0%) and 24
(96.0%) babies tested. PCR of 67 infant blood samples identified 5 HIV-positive (MTCT rate = 7.5%, 95%
confidence interval [CI]: 0.3%-16.6%). Mothers can administer nevirapine to themselves and their newborns
and can achieve low rates of perinatal HIV infection.
Kresge, K. J. 2005. "New strides in protecting infants from HIV. Researchers continue
quest to give pregnant women better options to prevent mother-to-child
transmission." IAVI Rep, 9(2):9-12.
Leroy, V., C. Sakarovitch, M. Cortina-Borja, J. McIntyre, H. Coovadia, F. Dabis, M. L.
Newell, J. Saba, G. Gray, C. Ndugwa, C. Kilewo, A. Massawe, P. Kituuka, P.
Okong, A. Grulich, H. von Briesen, J. Goudsmit, G. Biberfeld, G. Haverkamp, G.
J. Weverling, and J. M. Lange. 2005. "Is there a difference in the efficacy of
peripartum antiretroviral regimens in reducing mother-to-child transmission of
HIV in Africa?" Aids, 19(16):1865-75.
BACKGROUND: Peripartum antiretroviral regimens have been shown to prevent mother-to-child
transmission of HIV (MTCT) in randomized clinical trials; however, direct comparison of published results is
impossible given methodological and population differences. OBJECTIVE: To directly compare the efficacy
of different antiretroviral regimens in reducing the risk of 6-week MTCT rate in African breastfeeding
populations. METHODS: Pooled analysis including all mother-infant pairs from any relevant trial: West
African ZDV-placebo trials, Petra ZDV+3TC [two regimens A (pre/intra/post-partum) and B (intra/postpartum), placebo from Uganda and Tanzania], SAINT (NVP and Petra arm B), HIVNET012 (NVP, ultra short
ZDV pp) and the Vitamin A trial (as placebo arm in South Africa). Peripartum HIV infection was any positive
RNA or DNA polymerase chain reaction test < day 60. The MTCT risk was estimated at 6 weeks for each
treatment arm and compared with placebo or single-dose NVP using logistic regression adjusting for
maternal CD4 cell count, breastfeeding and birthweight. RESULTS: Overall, 4125 singleton live-births were
included; 3629 (88%) were assessed for HIV status at 6 weeks of age. In comparison with placebo,
zidovudine + lamivudine (ZDV+3TC) arm A [adjusted odds ratio (AOR), 0.23; P < 0.0001], ZDV+3TC arm B
(AOR, 0.49; P < 0.001), antenatal ZDV short (AOR, 0.55; P = 0.006) and nevirapine (NVP) (AOR, 0.60; P =
0.0007) significantly reduced MTCT. In comparison with NVP, only the longest regimen of ZDV+3TC (AOR,
0.39, P < 0.0005) was significantly more effective. CONCLUSION: These results are in line with current
World Health Organisation guidelines suggesting equivalence of choice between single-dose NVP and
short-course ZDV, and confirm the greater efficacy of ZDV+3TC than with any single antiretroviral drug.
Maclean, C. C. and J. S. Stringer. 2005. "Potential cost-effectiveness of maternal and
infant antiretroviral interventions to prevent mother-to-child transmission during
breast-feeding." J Acquir Immune Defic Syndr, 38(5):570-7.
INTRODUCTION: One-third of maternal-to-child HIV transmission occurs during breast-feeding (BF).
Several trials are currently evaluating the efficacy of postpartum antiretrovirals to reduce BF transmission.
METHODS: This study used Markov modeling to define the circumstances under which the following
interventions would be cost-effective: BF for 6 months with daily infant nevirapine (NVP) prophylaxis;
maternal combination antiretroviral therapy (ART) during pregnancy and for 6 months of BF; and maternal
combination ART only for women who meet CD4 criteria. Each was compared to: BF for 12 months; BF for 6
Page 11 of 56
months; and formula feeding for 12 months. Strategies were evaluated for a hypothetical cohort of 40,000
pregnant women in sub-Saharan Africa, in the context of available voluntary counseling and testing in
antenatal care. Model estimates were derived from the literature and local sources. Sensitivity analyses
were performed on uncertain estimates. The perspective used was that of a government health district.
RESULTS: Using base case estimates, BF for 6 months was the economically preferred strategy: it cost
806,995 dollars and generated 446,208 quality-adjusted life-years (QALYs). Providing daily infant NVP cost
an additional 93,638 dollars and generated 1183 additional QALYs, but its incremental cost-effectiveness
ratio (ICER) of 79 dollars/QALY exceeded the standard willingness to pay (64 dollars/QALY) for most
resource-poor settings. Maternal combination ART was potentially very effective but too costly for most
resource-poor settings (ICER: 87 dollars/QALY). In order for daily infant NVP during BF to be preferred, it
must have >/=44% relative efficacy or cost </=5.00 dollars/mo. If NVP were donated, it would only have to
be minimally effective to be the economically preferred strategy. If ART cost </=34.50 dollars/mo, ART to all
mothers would become the preferred strategy under our assumption of 82% efficacy. CONCLUSIONS:
Providing antiretrovirals during BF represents a promising alternative, should their effectiveness, and
feasibility be proven.
Manzi, M., R. Zachariah, R. Teck, L. Buhendwa, J. Kazima, E. Bakali, P. Firmenich, and
P. Humblet. 2005. "High acceptability of voluntary counselling and HIV-testing
but unacceptable loss to follow up in a prevention of mother-to-child HIV
transmission programme in rural Malawi: scaling-up requires a different way of
acting." Trop Med Int Health, 10(12):1242-50.
SETTING: Thyolo District Hospital, rural Malawi. OBJECTIVES: In a prevention of mother-to-child HIV
transmission (PMTCT) programme, to determine: the acceptability of offering 'opt-out' voluntary counselling
and HIV-testing (VCT); the progressive loss to follow up of HIV-positive mothers during the antenatal period,
at delivery and to the 6-month postnatal visit; and the proportion of missed deliveries in the district. DESIGN:
Cohort study. METHODS: Review of routine antenatal, VCT and PMTCT registers. RESULTS: Of 3136 new
antenatal mothers, 2996 [96%, 95% confidence interval (CI): 95-97] were pre-test counselled, 2965 (95%,
CI: 94-96) underwent HIV-testing, all of whom were post-test counselled. Thirty-one (1%) mothers refused
HIV-testing. A total of 646 (22%) individuals were HIV-positive, and were included in the PMTCT
programme. Two hundred and eighty-eight (45%) mothers and 222 (34%) babies received nevirapine. The
cumulative loss to follow up (n=646) was 358 (55%, CI: 51-59) by the 36-week antenatal visit, 440 (68%, CI:
64-71) by delivery, 450 (70%, CI: 66-73) by the first postnatal visit and 524 (81%, CI: 78-84) by the 6-month
postnatal visit. This left just 122 (19%, CI: 16-22) of the initial cohort still in the programme. The great
majority (87%) of deliveries occurred at peripheral sites where PMTCT was not available. CONCLUSIONS:
In a rural district hospital setting, at least 9 out of every 10 mothers attending antenatal services accepted
VCT, of whom approximately one-quarter were HIV-positive and included in the PMTCT programme. The
progressive loss to follow up of more than three-quarters of this cohort by the 6-month postnatal visit
demands a 'different way of acting' if PMTCT is to be scaled up in our setting.
McIntyre, J. 2005. "Preventing mother-to-child transmission of HIV: successes and
challenges." Bjog, 112(9):1196-203.
Mother-to-child transmission of HIV continues to be a major cause of infant morbidity and mortality in
resource-poor settings. Intrapartum and postpartum nevirapine-based regimens have been introduced in
many settings. New research has shown that better efficacy can be achieved with the addition of single-dose
nevirapine to short course zidovudine regimens, and that selection of nevirapine-resistant virus can be
reduced with a short postpartum combination antiretroviral cover. Women who need antiretroviral therapy for
their own health should receive it in pregnancy, and access for pregnant women needs to be expanded
urgently. The reduction of transmission through breastfeeding remains a challenge.
—. 2005. "Prevention of mother-to-child transmission of HIV: treatment options." Expert
Rev Anti Infect Ther, 3(6):971-80.
Mother-to-child transmission of HIV-1 is responsible for 1800 new infections in children daily. The use of
antiretroviral therapy can significantly reduce the risk of transmission. In settings where highly active
antiretroviral therapy is available, mother-to-child transmission rates have been reduced to less than 2%, in
Page 12 of 56
the absence of breastfeeding. Women who require ongoing highly active antiretroviral therapy for their own
health should receive this in pregnancy, which is also very effective in preventing transmission. Where
resources allow, combination highly active antiretroviral therapy can also be used for preventing mother-tochild transmission in those women who do not yet need to receive ongoing treatment. The potential side
effects of highly active antiretroviral therapy must be considered in pregnant women and their infants. Where
highly active antiretroviral therapy is not possible, a dual combination regimen of antepartum zidovudine with
single-dose nevirapine to mother and baby can reduce transmission to below 5%. In many places, the only
available option is single-dose nevirapine to mother and baby, which is effective in halving transmission risk,
although the effectiveness in practice will be influenced by continued infection through breastfeeding, and by
program factors such as the uptake of HIV testing. Exposure to nevirapine for mother-to-child transmission
prevention can select for resistant virus in the majority of women. While the long-term implications of this are
not completely clear, this selection can be reduced by the addition of short courses of postpartum
zidovudine and lamivudine.
Moodley, J. and J. L. Wennberg. 2005. "HIV in pregnancy." Curr Opin Obstet Gynecol,
17(2):117-21.
PURPOSE OF REVIEW: This review discusses recent articles on various aspects of the prevention of
mother-to-child transmission during pregnancy and delivery. RECENT FINDINGS: Rapid human
immunodeficiency virus (HIV) testing of women in labour whose status is not known allows the prompt
treatment of mother and baby to reduce transmission risk. The feared clinical resistance in the mother after
treatment with a single dose of nevirapine has been confirmed. Strategies are required to minimize this
resistance and allow the use of nevirapine for treatment of the mother. There are new findings of
mitochondrial toxicity in babies who have been exposed to anti-retroviral medicines during pregnancy or
delivery, but the clinical implications are not clear. Long-term follow-up of exposed children is required.
Resource-poor countries are starting to use multiple drugs to further reduce transmission to the infant.
These efforts are reducing the rates of transmission to the level found in affluent countries. SUMMARY:
Improvements in treatment continue to reduce the risk of HIV transmission from mother to child in resourcepoor countries, but subsequent maternal resistance continues to be a problem since treatment for the
mother's health is now possible. The long-term effects on the infant are still not understood.
Mpairwe, H., L. Muhangi, P. B. Namujju, A. Kisitu, A. Tumusiime, M. Muwanga, J. A.
Whitworth, S. Onyango, B. Biryahwaho, and A. M. Elliott. 2005. "HIV risk
perception and prevalence in a program for prevention of mother-to-child HIV
transmission: comparison of women who accept voluntary counseling and testing
and those tested anonymously." J Acquir Immune Defic Syndr, 39(3):354-8.
OBJECTIVE: To determine whether data from voluntary counseling and testing (VCT)/prevention of motherto-child transmission (PMTCT) programs can be used for HIV surveillance. METHODS: Women attending
an antenatal clinic at the district hospital in Entebbe, Uganda, from May 2002 to April 2003 were offered
counseling and HIV testing with same-day results (VCT) and nevirapine for PMTCT was provided for HIVpositive women and their babies. Those who declined VCT were tested for HIV anonymously. RESULTS:
Overall, 2635 women accepted VCT; 883 were tested anonymously. HIV prevalence was higher in VCT than
in anonymously tested women in the first month of the program (20% vs. 11%, P=0.05) and in months with
<70% VCT uptake (17% vs. 8%, P<0.001) but was similar in months with high uptake. Uptake of VCT was
higher in women who had risk factors for HIV, especially those who believed themselves to have been
exposed (84% vs. 73%, P<0.001). CONCLUSION: There was a bias to accepting VCT in women with HIV,
or risk factors for HIV infection, the former most apparent when there was low coverage. Data from
VCT/PMTCT programs cannot replace anonymous surveillance for monitoring of HIV epidemic trends where
coverage is incomplete within clinics or communities.
Quian, J., A. Visconti, S. Gutierrez, A. Galli, M. Maturo, V. Galeano, M. Serra, and M.
Lioni. 2005. "[Detection of HIV infection in pregnant women by rapid testing: a
successful strategy to reduce its vertical transmission]." Rev Chilena Infectol,
22(4):321-6.
Page 13 of 56
A high percentage of Uruguayan pregnant women are not under medical control. As a consequence,
vertically transmission of HIV infection reaches to 50%. The aim of this study was to know the prevalence of
HIV infection in pregnant women who did not know their serological status and to decrease mother-to-child
transmission. PATIENTS AND METHODS: from January 2002 to January 2004 the HIV rapid test was
performed to every pregnant woman that assisted to a public Uruguayan hospital unaware of her condition.
The proper prophylactic decisions were adopted according to gestational age. The newborn infants were
classified according to CDC criteria. HIV infection prevalence in pregnant women and in their newborn
infants was calculated. RESULTS: there were 34,338 obstetric consultations and 4,599 rapid tests were
performed. Fifty-nine turned out positive in 58 women, 8 of them knew their serological status previously.
The HIV infection prevalence was 1.1% (IC95% 0.8-1.4). Five cases were discharged: 1 false positive and 3
miscarriages and 1 abortion. Ten women dropped out in the follow up. Twelve women received TARV during
pregnancy for over a week. Thirty-nine infants could be controlled: 33 seroreverted, 4 were exposed and 2
became infected. Mother-to-child transmission was 5.1%. If all patients who dropped out the follow up were
infected, the transmission rate should be of 20.4%; therefore the infection would have been prevented in 16
children. As many women and children were lost, other complementary actions as counseling and social
worker interview should be adopted in order to improve the yield of rapid test screening strategy.
Schwitzer, G., G. Mudur, D. Henry, A. Wilson, M. Goozner, M. Simbra, M. Sweet, and
K. A. Baverstock. 2005. "What are the roles and responsibilities of the media in
disseminating health information?" PLoS Med, 2(7):e215.
BACKGROUND TO THE DEBATE: In December 2004 three news stories in the popular press suggested
that the side effects of single-dose nevirapine, which has been proven to prevent mother-to-child
transmission of HIV, had been covered up. Many HIV experts believed that the stories were unwarranted
and that they would undermine use of the drug, leading to a rise in neonatal HIV infection. The controversy
surrounding these stories prompted the PLoS Medicine editors to ask health journalists, and others with an
interest in media reporting of health, to share their views on the roles and responsibilities of the media in
disseminating health information.
Semrau, K., L. Kuhn, C. Vwalika, P. Kasonde, M. Sinkala, C. Kankasa, E. Shutes, G.
Aldrovandi, and D. M. Thea. 2005. "Women in couples antenatal HIV counseling
and testing are not more likely to report adverse social events." Aids, 19(6):6039.
BACKGROUND: Couple counseling has been promoted as a strategy to improve uptake of interventions to
prevent mother-to-child HIV transmission (pMTCT) and to minimize adverse social outcomes associated
with disclosure of HIV status. OBJECTIVES: We tested whether women counseled antenatally as part of a
couple were more likely to accept HIV testing and nevirapine in a pMTCT program, and whether they would
be less likely to experience later adverse social events than women counseled alone. METHODS: A pMTCT
program that included active community education and outreach to encourage couple counseling and testing
was implemented in two antenatal clinics in Lusaka, Zambia. A subset of HIV-positive women was asked to
report their experience of adverse social events 6 months after delivery. Couple-counseled women were
compared with individual-counseled women stratified by whether or not they had disclosed their HIV status
to their partners. RESULTS: Nine percent (868) of 9409 women counseled antenatally were counseled with
their husband. Couple-counseled women were more likely to accept HIV testing (96%) than women
counseled alone (79%); however uptake of nevirapine was not improved. Six months after delivery, 28% of
324 HIV-positive women reported at least one adverse social event (including physical violence, verbal
abuse, divorce or separation). There were no significant differences in reported adverse social events
between couple- and individual-counseled women. CONCLUSIONS: Couple counseling did not increase the
risk of adverse social events associated with HIV disclosure. Support services and interventions to improve
social situations for people living with HIV need to be further evaluated.
Shapiro, R. L., T. Ndung'u, S. Lockman, L. M. Smeaton, I. Thior, C. Wester, L. Stevens,
G. Sebetso, S. Gaseitsiwe, T. Peter, and M. Essex. 2005. "Highly active
antiretroviral therapy started during pregnancy or postpartum suppresses HIV-1
RNA, but not DNA, in breast milk." J Infect Dis, 192(5):713-9.
Page 14 of 56
BACKGROUND: The ability of highly active antiretroviral therapy (HAART) to reduce human
immunodeficiency virus type 1 (HIV-1) RNA and DNA in breast milk has not been described. METHODS:
We compared breast-milk HIV-1 RNA and DNA loads of women in Botswana who received HAART
(nevirapine, lamivudine, and zidovudine) and women who did not receive HAART. RESULTS: Women in the
HAART group received treatment for a median of 98 days (range, 67-222 days) at the time of breast-milk
sampling; 23 (88%) of 26 had whole breast-milk HIV-1 RNA loads <50 copies/mL, compared with 9 (36%) of
25 women who did not receive HAART (P=.0001). This finding remained significant in a multivariate logisticregression model (P = .0006). The whole-milk HIV-1 DNA load was unaffected by HAART. Of women who
received HAART, 13 (50%) of 26 had HIV-1 DNA loads <10 copies/10(6) cells, compared with 15 (65%) of
23 who did not receive HAART (P = .39). CONCLUSIONS: HAART suppressed cell-free HIV-1 RNA in
breast milk and may therefore reduce mother-to-child transmission (MTCT) of HIV-1 via breast-feeding.
However, HAART initiated during pregnancy or early after delivery had no apparent effect on cell-associated
HIV-1 DNA loads in breast milk. Clinical trials to determine MTCT among breast-feeding women receiving
HAART are needed.
Sint, T. T., F. Dabis, C. Kamenga, N. Shaffer, and I. F. de Zoysa. 2005. "Should
nevirapine be used to prevent mother-to-child transmission of HIV among women
of unknown serostatus?" Bull World Health Organ, 83(3):224-8.
At present, HIV testing and counselling during pregnancy represent the key entry point for women to learn
their serostatus and for them to access, if they are HIV-positive, specific interventions to reduce mother-tochild transmission (MTCT) of HIV. However, the provision and uptake of testing and counselling services are
inadequate, and many pregnant women in countries most affected by the HIV/AIDS epidemic remain
unaware of their HIV status. The offer of single-dose nevirapine prophylaxis to women whose HIV status is
unknown at the time of delivery has been proposed to circumvent these problems in high-prevalence
settings. The potential advantages and disadvantages of three different programme approaches are
considered: targeted programmes in which antiretroviral drugs are offered only to women who are known to
be HIV-positive; combined programmes in which nevirapine prophylaxis is offered to women whose
serostatus remains unknown at the time of delivery despite targeted programme inputs; and universal
nevirapine prophylaxis programmes in which HIV testing and counselling are not available and all pregnant
women, regardless of their serostatus, are offered nevirapine prophylaxis.
Stringer, J. S., M. Sinkala, C. C. Maclean, J. Levy, C. Kankasa, A. Degroot, E. M.
Stringer, E. P. Acosta, R. L. Goldenberg, and S. H. Vermund. 2005.
"Effectiveness of a city-wide program to prevent mother-to-child HIV transmission
in Lusaka, Zambia." Aids, 19(12):1309-15.
OBJECTIVE: To determine the population effectiveness of a city-wide perinatal HIV prevention program.
DESIGN: An anonymous surveillance of newborn cord blood for HIV serology and nevirapine (NVP).
METHODS: All 10 public-sector delivery centers in Lusaka, Zambia participated. All mother-infant pairs
delivering during the 12-week surveillance period at the participating centers and who received antenatal
care at a public-sector facility in Lusaka were included in the study. The main outcome measure was
population NVP coverage, defined as the proportion of HIV-infected women and HIV-exposed infants in the
population that ingested NVP. RESULTS: Of 8787 women in the surveillance population, 7204 (82%) had
been offered antenatal HIV testing, of which 5149 (71%) had accepted, and of which 5129 (99%) had
received a result. Overall, 2257 of 8787 (26%) were cord seropositive. Of the 1246 (55%) cord blood
seropositive women who received an antenatal HIV test result, 1112 (89%) received a positive result; the
other 134 comprise seroconverters and clerical errors. Only 751 of 1112 (68%) women who received a
positive antenatal test result and a NVP tablet for ingestion at labor onset had NVP detected in the cord
blood (i.e., maternal non-adherence rate was 32%). A total of 675 infants born to 751 adherent mothers
(90%) received NVP before discharge. Thus, only 675 of 2257 (30%) seropositive mother-infant pairs in the
surveillance population received both a maternal and infant dose of NVP. CONCLUSIONS: Successful
perinatal HIV prevention requires each mother-infant pair to negotiate a cascade of events that begins with
offering HIV testing and continues through adherence to the prescribed regimen. This novel surveillance
demonstrates that failures occur at each step, resulting in reduced coverage and diminished program
effectiveness.
Page 15 of 56
Teerawattananon, Y., T. Vos, V. Tangcharoensathien, and M. Mugford. 2005. "Costeffectiveness of models for prevention of vertical HIV transmission - voluntary
counseling and testing and choices of drug regimen." Cost Eff Resour Alloc, 3:7.
OBJECTIVES: From a health care provider prospective, to assess the cost-effectiveness of four
Antiretroviral therapy (ART) regimens given in addition to voluntary counselling and testing (VCT) for
preventing mother-to-child transmission of HIV: a) Zidovudine (AZT); b) Nevirapine (NVP); c) a combination
of AZT for early antenatal attenders and NVP for late arrivals; and d) combined administration of AZT and
NVP and to assess the incremental cost-effectiveness of adding a second VCT session in late pregnancy.
DESIGN & SETTING: We examine a hypothetical cohort of 100,000 pregnancies as a decision model. Cost
and outcome parameters are estimated as they would apply under Thai routine health service conditions.
Effectiveness probabilities are based on best available evidence, from systematic reviews where possible.
The main outcome is the number of cases of paediatric HIV averted. RESULTS: The combining
administration of AZT and NVP is the most cost-effective drug option. One VCT session with AZT+NVP
averts 337 cases of infection at 556 USD per case averted, while two VCT with the same drug regimen
averts 16 additional cases at cost of 1,266 USD per infection averted. The incremental cost-effectiveness
ratio of moving from 1VCT, AZT+NVP to 2VCT, AZT+NVP is 16,000 USD per additional averted case, which
is much lower than the recommended threshold value for HIV infection averted in Thailand. Multivariate
uncertainty analysis supports the findings, showing that at a threshold of 35,000 USD, 2VCT, AZT+NVP is
preferable to other VCT and drug strategies. CONCLUSION: Interventions for preventing mother-to-child
transmission of HIV are cost-effective. Further costs and negative effects of drug resistance, are unlikely to
outweigh the social benefits of reduce transmission of HIV. This model suggests that the new drug regimen
is a cost-effective option in the Thai health system at currently accepted thresholds for adopting health
technologies.
Thorne, C. and M. L. Newell. 2005. "The safety of antiretroviral drugs in pregnancy."
Expert Opin Drug Saf, 4(2):323-35.
Advances in HIV therapy and mother-to-child transmission (MTCT) prophylaxis have led to increasing use of
antiretroviral drugs in pregnancy. Highly active antiretroviral therapy in pregnancy has been associated with
prematurity, pre-eclampsia and gestational diabetes. Women may be at increased risk of nevirapineassociated hepatotoxicity but whether or not pregnancy is an additional risk is uncertain. Although animal
studies suggest a possibility of congenital abnormalities with specific antiretrovirals, such as efavirenz,
results from registries and cohort studies do not support an excess of congenital malformations associated
with in utero antiretroviral exposure. Concerns regarding the health of uninfected, antiretroviral-exposed
children include the potential for cancers, mitochondrial disease and haematological abnormalities.
However, the absence of any excess mortality in large observational cohort studies of uninfected,
antiretroviral therapy-exposed children born to HIV-infected women is reassuring. Based on current
knowledge, the immense benefits of antiretroviral prophylaxis in reducing the risk of MTCT, far outweigh the
potential for adverse effects.
—. 2005. "Treatment options for the prevention of mother-to-child transmission of HIV."
Curr Opin Investig Drugs, 6(8):804-11.
Vertically acquired HIV infection has been virtually eliminated in developed countries through the use of
highly active antiretroviral therapy (HAART), reducing mother-to-child transmission rates to below 1 to 2%.
However, with the increasing use of HAART, particularly when initiated before or during early pregnancy,
safety and toxicity issues for both women and infants have gained significance. In less developed countries,
the effectiveness of simpler and less costly antiretroviral strategies has been shown to be acceptable;
however, the high prevalence of resistance associated with the use of monotherapy, in particular single dose
nevirapine, has meant increasing attention focused on the use of combination therapy in these countries.
Toni, T. D., B. Masquelier, E. Lazaro, M. Dore-Mbami, F. O. Ba-Gomis, Y. Tea-Diop, K.
Kouakou, J. Diby, E. Sia, S. Soppi, S. Essien, M. H. Schrive, P. Pinson, H.
Chenal, and H. J. Fleury. 2005. "Characterization of nevirapine (NVP) resistance
mutations and HIV type 1 subtype in women from Abidjan (Cote d'Ivoire) after
Page 16 of 56
NVP single-dose prophylaxis of HIV type 1 mother-to-child transmission." AIDS
Res Hum Retroviruses, 21(12):1031-4.
Nevirapine (NVP) single dose is widely used in developing countries to prevent HIV-1 mother-to-child
transmission. However, this regimen selects key drug resistance mutations that can impair further HAART
efficacy. We studied the HIV-1 reverse transcriptase genotype from 29 Ivoirian women 1 month after an
NVP single-dose prophylaxis. NVP resistance mutations were observed in six (20.7%) women. The majority
of the isolates were CRF02_AG. These results confirm previous studies and suggest the need for different
prophylaxis regimens in this setting.
van't Hoog, A. H., D. A. Mbori-Ngacha, L. H. Marum, J. A. Otieno, A. O. Misore, L. W.
Nganga, and K. M. Decock. 2005. "Preventing mother-to-child transmission of
HIV in Western Kenya: operational issues." J Acquir Immune Defic Syndr,
40(3):344-9.
OBJECTIVES: To improve uptake in a program to prevent mother-to-child HIV transmission and describe
lessons relevant for prevention of mother-to-child transmission programs in resource-poor settings.
METHODS: Implementation of a pilot project that evaluates approaches to increase program uptake at
health facility level at New Nyanza Provincial General Hospital, a public hospital in western Kenya, an area
with high HIV prevalence. Client flow was revised to integrate counseling, HIV testing, and dispensing of
single-dose nevirapine into routine antenatal services. The number of facilities providing PMCT services was
expanded to increase district-wide coverage. Main outcome measures were uptake of counseling, HIV
testing, nevirapine, and estimated program impact. RESULTS: Uptake of counseling and testing improved
from 55 to 68% (P < 0.001), nevirapine uptake from 57% to 70% (P < 0.001), and estimated program impact
from 15% to 23% (P = 0.03). Aggregate reports compare well with computer-entered data. CONCLUSION:
Addressing institutional factors can improve uptake, but expected program impact remains low for several
reasons, including relatively low efficacy of the intervention and missed opportunities in the labor room.
Vazquez, E. 2005. "12th Retrovirus Conference. Viramune to prevent mother-to-child
transmission. Moving from to consensus." Posit Aware, 16(3):28, 31.
Volmink, J. and U. Mahlat. 2005. "HIV: mother to child transmission." Clin Evid,
(13):823-33.
Welty, T. K., M. Bulterys, E. R. Welty, P. M. Tih, G. Ndikintum, G. Nkuoh, J. Nkfusai, J.
Kayita, J. N. Nkengasong, and C. M. Wilfert. 2005. "Integrating prevention of
mother-to-child HIV transmission into routine antenatal care: the key to program
expansion in Cameroon." J Acquir Immune Defic Syndr, 40(4):486-93.
With funds from Elizabeth Glaser Pediatric AIDS Foundation, the Cameroon Baptist Convention Health
Board implemented a program to prevent mother-to-child transmission of HIV-1 (PMTCT) as part of its
routine antenatal care, with single-dose maternal and infant peripartum nevirapine (NVP) prophylaxis of HIVpositive mothers and their babies. Nurses, midwives, nurse aides, and trained birth attendants counseled
pregnant women, obtained risk factor data, and offered free HIV testing with same-day results. From
February 2000 through December 2004, this program rapidly expanded to 115 facilities in 6 of Cameroon's
10 provinces, not only to large hospitals but to remote health centers staffed by trained birth attendants. We
trained 690 health workers in PMTCT and counseled 68,635 women, 91.9% of whom accepted HIV testing.
Of 63,094 women tested, 8.7% were HIV-1-positive. Independent risk factors for HIV-1 infection included
young age at first sexual intercourse, multiple sex partners, and positive syphilis serology (P < 0.001 for
each). We counseled 98.7% of positive and negative mothers on a posttest basis. Of 5550 HIV-positive
mothers, we counseled 5433 (97.9%) on single-dose NVP prophylaxis. Consistent training and
programmatic support contributed to rapid upscaling and high uptake and counseling rates.
Page 17 of 56
Adeothy-Koumakpai, S., C. N. Monnykosso, M. D'Almeida, J. Houansou, G. Batossi, I.
Hodonou, R. Agossou, I. Adeyanju, J. Testa, and J. L. Portal. 2004. "[Prevention
of HIV mother to child transmission in Cotonou: child follow-up]." Arch Pediatr,
11(12):1425-9.
The aim of this survey was to analyse the constraints of implementing on a larger scale the protocol of
prevention of HIV/AIDS from mother to child by Nevirapine intake. This survey takes stock of the
components of the children medical care follow-up. PATIENTS AND METHODOLOGY: Here is a straight
line survey on 231 newborns from 222 screened mothers during pregnancy in 36 Health Centres in Cotonou
and suburbia. Nevirapine has been administered in a single dose of 200 mg to mothers during labour and a
dosage of 7 mg to the infant at birth. These infants have been steadily followed-up from 13 June 2000 to 30
April 2002. Exclusively feeding either on artificial milk or breastfeeding and a premature weaning at four
months of age have been recommended. PCR screening has been conducted at one and six months of age
or one month after the effective weaning. Cotrimoxazole has been systematically administered at six weeks.
RESULTS: HIV/AIDS sero prevalence was globally evaluated at 4% in the screened pregnant women. One
hundred and ninety seven mothers and children have effectively benefited from nevirapine intakes and this
protocol has been adequately observed in 51% cases. The medical check-up rate was 18.5%. The average
age of children under medical care was 10.8 months at the end of the study. The mother to child
transmission rate was globally estimated at 20.4% and 7% in an optimal situation (the protocol was
observed and the rate of CD4 above 500). In case of breastfeeding exclusively followed by a premature
weaning in most cases, the average age of effective weaning was 8.3 months. Twenty-three children died
during medical care follow-up basically from dehydration brought about by diarrhea and vomiting during
weaning period. CONCLUSION: The survey confirms the potency of nevirapine in preventing HIV
transmission from mother to child in non immunosuppressed women and lays emphasis on real problems for
which appropriate solutions should be found before the implementation on a larger scale of this protocol.
Bajunirwe, F., I. Massaquoi, S. Asiimwe, M. R. Kamya, E. J. Arts, and C. C. Whalen.
2004. "Effectiveness of nevirapine and zidovudine in a pilot program for the
prevention of mother-to-child transmission of HIV-1 in Uganda." Afr Health Sci,
4(3):146-54.
BACKGROUND: Single dose nevirapine and a short course of zidovudine (AZT) are now administered in
most hospitals in Uganda to prevent mother-to-child transmission (MTCT) of HIV. The effectiveness of these
antiretroviral (ARV) regimens has been shown in the clinical trials but has not been demonstrated outside
the clinical trials setting in this country. OBJECTIVES: The study evaluated the effectiveness of short course
ARV regimens in a pilot program to prevent mother-to-child transmission of HIV and determined the risk
factors for perinatal transmission. METHODS: Cross-sectional study design was used to compare perinatal
transmission rates of HIV in two sets of mothers: ARV-treated mothers and ARV-untreated mothers.
RESULTS: 109 treated and 90 naive mother-infant pairs were recruited. HIV transmission rates were similar
in the nevirapine (10/61) and AZT (8/48) groups (16.4% vs. 16.7%) respectively but higher in the naive
group (43/90 48%, p= 0.0001). ARV therapy offers a protective effect against MTCT of HIV (Adjusted Odds
Ratio 0.22 95%CI 0.09, 0.54) but mothers in Stage 1 and 2 of disease were more likely to benefit from this
intervention than mothers in Stage 3 and 4. CONCLUSION: In this community-based observational study,
ARV reduces the risk of perinatal transmission of HIV but does not eliminate the risk completely. Early
screening of asymptomatic pregnant women will identify a group of mothers more likely to benefit from the
intervention.
Brusamolino, E. and G. Maffi. 2004. "Health cooperation in an hospital of a rural area of
Ivory Coast: analysis of the priorities and of the different levels at which
cooperation can take place." Crit Rev Oncol Hematol, 49(1):43-51.
This paper critically reviews an experience of health cooperation in an hospital of a rural area of Ivory Coast.
This particular situation is analysed in the more general frame of health problems in low-income countries
and may suggest priorities for international health cooperation. The analysis of the main causes of avoidable
death in poor countries does indicate targets and tools of intervention. In this case, the target was the
reduction of infant mortality from anaemia of different origin and from HIV-1 mother-to-infant transmission.
The major tool for intervention was the partnership between an Italian teaching and research hospital and
Page 18 of 56
the African hospital, with the catalyst of a non-governmental organisation. This paper analyses the different
levels at which cooperation developed in this project, from sheer economic support to the implementation of
disease-oriented twinning programs that can improve health care and strengthen research capacity on both
sides. Besides, medical, ethical and social implications of the ongoing cooperation program are discussed,
with particular reference to the problems of preventing mortality from severe anaemia (diet fortification in
children and pregnancy and transfusional guidelines in severe malaria) and of preventing mother-to-child
neonatal transmission of HIV-1 infection (counselling and testing pregnant women for HIV-1, nevirapine
administering to the mother and the baby and breast-feeding).
Chama, C. M., B. M. Audu, and O. Kyari. 2004. "Prevention of mother-to-child
transmission of HIV at Maiduguri, Nigeria." J Obstet Gynaecol, 24(3):266-9.
The human immunodeficiency virus (HIV) can be transmitted vertically through the placenta in utero, during
labour and delivery and through breast milk. In Nigeria, about 5.8% of women attending antenatal clinics
were HIV infected as of December 2002. It was projected that by the end of the year 2002, there were about
849,000 orphans resulting from AIDS and about 755,000 established paediatric AIDS in this country.
Interventions to prevent mother-to-child transmission of HIV include voluntary counselling and testing (VCT),
administration of antiretroviral drugs (ARV), modification of obstetric practices and infant feeding options in
HIV infection. Over the period July 2002-June 2003, 262 pregnant women received VCT at the antenatal
clinic of the University of Maiduguri Teaching Hospital, and 207 (79%) agreed to be tested. Thirty-one
(11.8%) were HIV positive. The majority of the HIV positive mothers received nevirapine in labour while 35%
had combination ARV drugs in pregnancy. All the infants received nevirapine suspension within 72 hours of
delivery. Expensive and slow testing facilities, insufficient and inconsistent counsellors, lack of ARV drugs
for both mother and baby as well as unaffordable caesarean delivery were some of the constraints being
faced at this centre. It is recommended that the governments at various levels should show more
commitment to the programme of preventing mother-to-child transmission of HIV.
Cunningham, C. K., R. Balasubramanian, I. Delke, R. Maupin, L. Mofenson, A.
Dorenbaum, J. L. Sullivan, A. Gonzalez-Garcia, E. Thorpe, M. Rathore, and R. D.
Gelber. 2004. "The impact of race/ethnicity on mother-to-child HIV transmission
in the United States in Pediatric AIDS Clinical Trials Group Protocol 316." J
Acquir Immune Defic Syndr, 36(3):800-7.
The present analysis was designed to determine whether race/ethnicity was independently associated with
mother-to-child HIV-1 transmission risk in subjects enrolled in a trial of 2-dose intra-partum nevirapine in
combination with standard antiretroviral therapy and to determine what factors, including race/ethnicity,
predicted maternal viral suppression at the time of delivery. Women enrolled in Pediatric AIDS Clinical Trials
Group (PACTG) 316 from sites in the United States and Puerto Rico were included. Distribution of selected
maternal disease and treatment characteristics was assessed by race/ethnicity category. Logistic regression
models were fit to evaluate possible association of factors with HIV transmission and with viral load at
delivery. Variables associated with the outcome at P < 0.05 level were retained in the final models. Of 1052
women randomized at PACTG sites, 891 were included in the present analysis: 572 (64%) were black; 206
(23%) were Hispanic; and 113 (13%) were white. All women who had infected infants were black or Hispanic
(11/572 and 3/206, respectively), whereas none of the women identified as white had an infected infant
(0/113). This difference was not statistically significant (P = 0.54). White women had higher entry CD4 cell
counts and lower HIV-1 RNA at delivery than women of other races/ethnicities. Black and Hispanic women
were more likely than white women to start therapy during their current pregnancy but did not initiate
prenatal care later. In bivariate models that included antiretroviral type and variables that had values of P <
or = 0.25 in univariate analysis, time of antiretroviral initiation, time of prenatal care initiation, and
race/ethnicity each retained significance in predicting viral suppression at delivery. Race/ethnicity remained
predictive of viral suppression at delivery in a multivariate model incorporating all of these variables (P =
0.01). Higher HIV-1 RNA and lower CD4 cell counts in women identified as black or Hispanic have
significant implications for the health of these women and their newborns. Race/ethnicity is significant in
predicting viral suppression at the time of delivery.
Page 19 of 56
Dubuisson, J. G., J. R. King, J. S. Stringer, M. L. Turner, C. Bennetto, and E. P. Acosta.
2004. "Detection of nevirapine in plasma using thin-layer chromatography." J
Acquir Immune Defic Syndr, 35(2):155-7.
BACKGROUND: Nevirapine (NVP) is widely prescribed in resource-poor settings to pregnant women for
treatment and prevention of HIV infection. High rates of misreported adherence, however, have compelled
clinicians to find alternative methods to ensure systemic drug exposure. This report describes a fast,
inexpensive thin-layer chromatography (TLC) method to detect the presence of NVP in human plasma.
METHODS: Human plasma was spiked with various concentrations of NVP. NVP was subsequently isolated
using solid-phase extraction and visualized with TLC. Clinical samples with NVP concentrations
predetermined by high-performance liquid chromatography were used to validate the TLC method.
RESULTS: NVP was detected at concentrations as low as 60 ng/mL. The lower limit of detection was set at
100 ng/mL due to the clear spot definition at this concentration. The turnaround time for assay results
averages several hours, and costs associated with the assay are considerably below standard drug
quantitation techniques. CONCLUSION: TLC provides a rapid, sensitive, and economical tool to qualitatively
measure NVP in plasma. This method offers clinicians in resource-poor settings an alternative approach for
measuring adherence, particularly in developing-world regions where NVP use is common and there is an
immediate need to prevent mother-to-child HIV transmission.
Ekouevi, D. K., F. Rouet, R. Becquet, A. Inwoley, I. Viho, B. Tonwe-Gold, L. Bequet, F.
Dabis, and V. Leroy. 2004. "Immune status and uptake of antiretroviral
interventions to prevent mother-to-child transmission of HIV-1 in Africa." J Acquir
Immune Defic Syndr, 36(2):755-7.
The aim of this study performed in Abidjan, Cote d'Ivoire, was to describe the distribution of CD4+ T-cell
lymphocytes (CD4) in HIV-1-infected (HIV+) pregnant women diagnosed during prenatal voluntary
counseling and testing and to assess whether HIV-related immunodeficiency influenced the acceptance of
an antiretroviral (ARV) package (zidovudine beginning at 36 weeks of amenorrhea plus intrapartum
nevirapine) to prevent mother-to-child transmission. Between April and June 2002, a CD4 count was
systematically performed in all HIV+ women (n=221) in 5 antenatal clinics carrying out voluntary counseling
and testing. No difference in CD4 count was found in HIV+ women who did not return for their test result
(n=50) and those who were informed of their positive serostatus (n=171) (median CD4 count: 389/mm3 vs.
420/mm3; P=0.19). We also found a lack of difference in CD4 count in those who accepted ARV (n=72) and
those who did not but knew their HIV status (n=99) (median CD4 count: 405/mm3 vs. 425/mm3; P=0.47).
The overall uptake of the intervention (31.9%) appeared to be independent of the maternal immune status.
Eshleman, S. H., L. A. Guay, A. Mwatha, S. P. Cunningham, E. R. Brown, P. Musoke,
F. Mmiro, and J. B. Jackson. 2004. "Comparison of nevirapine (NVP) resistance
in Ugandan women 7 days vs. 6-8 weeks after single-dose nvp prophylaxis:
HIVNET 012." AIDS Res Hum Retroviruses, 20(6):595-9.
We compared nevirapine (NVP) resistance (NVPR) mutations in maternal plasma 7 days vs. 6-8 weeks after
single-dose NVP prophylaxis. In the HIVNET 012 trial, Ugandan women received a single dose of NVP in
labor for prevention of HIV-1 mother-to-child transmission. NVPR mutations were detected in 70 (25%) of
279 women 6-8 weeks after NVP. Samples collected 7 days after NVP were analyzed from a subset of
those 279 women. Genotyping was performed with the ViroSeq HIV-1 Genotyping System. NVPR was
analyzed using paired samples from 7 days and 6-8 weeks after NVP. Sixty-five women had genotyping
results obtained for samples collected at both 7 days and 6-8 weeks post-NVP. Twenty-one (32%) of those
women had NVPR mutations detected in one or both samples. This included three women with NVPR at 7
days only, seven with NVPR at 6-8 weeks only, and 11 with NVPR at both time points. Eight women had >1
NVPR mutation detected 7 days after NVP. Y181C was the most common NVPR mutation detected at 7
days, whereas K103N was the most common NVPR mutation detected at 6-8 weeks. We conclude that
NVPR may be detected in women as early as 7 days after single-dose NVP. Complex patterns of NVPR are
detected in some women. The Y181C NVPR mutation often fades from detection by 6-8 weeks. In contrast,
the K103N mutation emerges more slowly, but often remains detectable 6-8 weeks after NVP.
Page 20 of 56
Goulder, P. J., N. Blanckenberg, and K. Dong. 2004. "Nevirapine plus zidovudine to
prevent mother-to-child transmission of HIV." N Engl J Med, 351(19):2013-5;
author reply 2013-5.
Harvey, K. M., J. P. Figueroa, J. Tomlinson, Y. Gebre, S. Forbes, T. Toyloy, T.
Thompson, and K. Thompson. 2004. "An assessment of mother-to-child HIV
transmission prevention in 16 pilot antenatal clinics in Jamaica." West Indian Med
J, 53(5):293-6.
OBJECTIVES: This study aims to determine the number and age distribution of pregnant women testing
positive for HIV at 16 selected clinics in Jamaica between 2001 and 2002; the utilization of therapeutic
interventions to minimize the risk of mother-to-child transmission (MTCT) and the current status of the HIVexposed infants and, finally, the number of children who received testing for detection of HIV and to
calculate the incidence of MTCT in these children. METHODS: A retrospective study was carried out at
sixteen pilot clinic sites by examining the patient records for all confirmed HIV-positive pregnant mothers and
the resultant infants at these facilities for the period January 2001 to December 2002. RESULTS: One
hundred and twenty-three of 8116 pregnant women newly tested positive during the period January 2001 to
December 2002; however, 176 HIV+ women delivered. Fifty-three (30%) knew their HIV status prior to
participating in the programme. Sixty-two (1.4%) and 61 (1.6%) tested positive in 2001 and 2002,
respectively. One hundred and ten (77%) and 113 (83%) mothers and infants, respectively, received ARV
therapy, (92% - nevirapine, 8% - zidovudine). Twenty-three per cent of pregnant women received no ARV
Forty-four (25.0%) of the 176 infants had a documented ELISA HIV test before eighteen months of age,
none had a PCR test. The health status of 40 (23%) of these children was known: 30 (75%) were alive and
well, five of whom did not receive any ARV, one (2.5%) was alive and ill and nine (22.5%) were reported
dead, five of whom received ARV; 28.6% of infants who did not receive ARV were reported as either dead or
ill compared to 13.8% of those receiving ARV CONCLUSION: Though the majority of pregnant women
discovered their HIV status during pregnancy, a significant number got pregnant knowing that they were
HIV+. The majority of mothers and infants received ARV but the follow-up and testing of infants was limited.
Nevirapine is clearly protective in the prevention of MTCT of HIV and should be made universally
accessible. All infants delivered to HIV+ mothers should be identified and tested for HIV.
Herzmann, C. and H. Karcher. 2004. "Nevirapine plus zidovudine to prevent mother-tochild transmission of HIV." N Engl J Med, 351(19):2013-5; author reply 2013-5.
Johnson, N., A. A. Mullings, K. M. Harvey, G. Alexander, D. McDonald, M. F. Smikle, E.
Williams, P. Palmer, S. Whorms, J. P. Figueroa, and C. D. Christie. 2004. "HIV
seroprevalence, uptake of interventions to reduce mother-to-child transmission
and birth outcomes in greater Kingston, Jamaica." West Indian Med J, 53(5):297302.
BACKGROUND: The seroprevalence of HIV among pregnant women in the Caribbean is 2-3% and
increasing. The Kingston Paediatric and Perinatal HIV Programme is developing and implementing a unified
programme to eliminate mother-to-child transmission (MTCT) of HIV in Kingston, Jamaica. METHODS:
Pregnant women presenting to Kingston Metropolitan Antenatal Clinics, Victoria Jubilee Hospital, Spanish
Town Hospital and the University Hospital of the West Indies had HIV serology performed by ELISA, or by
the new Determine Rapid Test after receiving group counselling. HIV-positive women were referred to High
Risk Antenatal Clinics. Antiretroviral prophylaxis with zidovudine (AZT), or nevirapine was given. Care was
administered using a standard protocol by a multi-disciplinary team of public and academic healthcare
personnel. RESULTS: In year one, 19,414 women delivered Among 14,054 women who started antenatal
care for this period, 5,558 (40%) received group counselling and 7,383 (53%) received HIV-testing. During
the fourth quarter of follow-up, these comparative rates were 66% (2049/3 118) and 72% (2260/3118)
respectively. HIV seroprevalence overall was 2.1% (152/7 383). One hundred and seven HIV+ women at
varying gestational ages were identified in the programme, 72 had so far received AZT and nine nevirapine
(76%). 0f 84 deliveries, birth outcomes were 75 live births (89%), six neonatal deaths and four maternal
Page 21 of 56
deaths (all from HIV/AIDS). Major challenges include repeat pregnancies of 36% despite prior knowledge of
HIV seropositivity and poor partner notification with only 30% (32) having a HIV-test. Although rates of HIV
testing in pregnant women in Greater Kingston are increasing, rates of testing overall remain sub-optimal.
On the labour ward, there was sub-optimal identification of the HIV+ pregnant woman and administration of
AZT chemoprophylaxis, along with issues of patient confidentiality and stigma. CONCLUSION: This
programme needs strengthening in order to reduce maternal-fetal transmission of HIV in Greater Kingston,
Jamaica "pMTCT-PLUS, or comprehensive family-centred care, is the next step".
Jourdain, G., N. Ngo-Giang-Huong, S. Le Coeur, C. Bowonwatanuwong, P. Kantipong,
P. Leechanachai, S. Ariyadej, P. Leenasirimakul, S. Hammer, and M. Lallemant.
2004. "Intrapartum exposure to nevirapine and subsequent maternal responses
to nevirapine-based antiretroviral therapy." N Engl J Med, 351(3):229-40.
BACKGROUND: A single intrapartum dose of nevirapine for the prevention of mother-to-child transmission
of human immunodeficiency virus (HIV) leads to the selection of resistance mutations. Whether there are
clinically significant consequences in mothers who are subsequently treated with a nevirapine-containing
regimen is unknown. METHODS: We randomly assigned 1844 women in Thailand who received zidovudine
during the third trimester of pregnancy to receive intrapartum nevirapine or placebo. In the postpartum
period, 269 of the women with a CD4 count below 250 cells per cubic millimeter began a nevirapinecontaining antiretroviral regimen. Plasma samples were obtained 10 days post partum and analyzed for
resistance mutations. Plasma HIV type 1 (HIV-1) RNA was measured before the initiation of therapy and
three and six months thereafter. RESULTS: After six months of therapy, the HIV-1 RNA level was less than
50 copies per milliliter in 49 percent of the women who had received intrapartum nevirapine, as compared
with 68 percent of the women who had not received intrapartum nevirapine (P=0.03). Resistance mutations
to nonnucleoside reverse-transcriptase inhibitors were detectable in blood samples obtained 10 days post
partum from 32 percent of the women who had received intrapartum nevirapine; the most frequent mutations
were K103N, G190A, and Y181C. Among the women who had received intrapartum nevirapine, viral
suppression was achieved at six months in 38 percent of those with resistance mutations and 52 percent of
those without resistance mutations (P=0.08). An HIV-1 RNA level at or above the median of 4.53 log10
copies per milliliter before therapy and intrapartum exposure to nevirapine were independently associated
with virologic failure. After six months of therapy, there was no significant difference between groups in the
CD4 count (P=0.65). CONCLUSIONS: Women who received intrapartum nevirapine were less likely to have
virologic suppression after six months of postpartum treatment with a nevirapine-containing regimen. Our
data suggest the need for strategies to maximize the benefits of both antiretroviral prophylaxis against
mother-to-child transmission of HIV and antiretroviral therapy for mothers.
Kapoor, A., A. Kapoor, and S. N. Vani. 2004. "Prevention of mother to child
transmission of HIV." Indian J Pediatr, 71(3):247-51.
Perinatal transmission is the most common cause of HIV infection in pediatric population below the age of
15 years. Much progress has been made to decrease the risk of transmission than just offering the option of
medical termination of pregnancy to the mother. Future research is needed not only to develop the simple
preventive program, but also to make it more cost effective, acceptable and accessible to the general
population. Following review article focuses on the factors affecting the transmission of HIV, strategies for
prevention of MTCT with special reference to use of nevirapine and breast-feeding practices in HIV positive
mother. The role of counseling and voluntary testing is also stressed upon.
Lallemant, M., G. Jourdain, S. Le Coeur, J. Y. Mary, N. Ngo-Giang-Huong, S.
Koetsawang, S. Kanshana, K. McIntosh, and V. Thaineua. 2004. "Single-dose
perinatal nevirapine plus standard zidovudine to prevent mother-to-child
transmission of HIV-1 in Thailand." N Engl J Med, 351(3):217-28.
BACKGROUND: Although zidovudine prophylaxis decreases the rate of transmission of the human
immunodeficiency virus (HIV) type 1 substantially, a large number of infants still become infected. We
hypothesized that the administration, in addition to zidovudine, of a single dose of oral nevirapine to mothers
during labor and to neonates would further reduce transmission of HIV. METHODS: We conducted a
randomized, double-blind trial of three treatment regimens in Thai women who were receiving zidovudine
Page 22 of 56
therapy during the third trimester of pregnancy. In one group, mothers and infants received a single dose of
nevirapine (nevirapine-nevirapine regimen); in another, mothers and infants received nevirapine and
placebo, respectively (nevirapine-placebo regimen); and in the last, mothers and infants received placebo
(placebo-placebo regimen). The infants also received one week of zidovudine therapy and were formula-fed.
The end point of the study was infection with HIV in the infants, established by virologic testing. RESULTS:
Between January 15, 2001, and February 28, 2003, a total of 1844 Thai women were enrolled. At the first
interim analysis, the independent data monitoring committee stopped enrollment in the placebo-placebo
group. Among women who delivered before the interim analysis, the as-randomized Kaplan-Meier estimates
of the transmission rates were 1.1 percent (95 percent confidence interval, 0.3 to 2.2) in the nevirapinenevirapine group and 6.3 percent (95 percent confidence interval, 3.8 to 8.9) in the placebo-placebo group
(P<0.001). The final per-protocol transmission rate in the nevirapine-nevirapine group, 1.9 percent (95
percent confidence interval, 0.9 to 3.0), was not significantly inferior to the rate in the nevirapine-placebo
group (2.8 percent; 95 percent confidence interval, 1.5 to 4.1). Nevirapine had an effect within subgroups
defined by known risk factors such as viral load and CD4 count. No serious adverse effects were associated
with nevirapine therapy. CONCLUSIONS: A single dose of nevirapine to the mother, with or without a dose
of nevirapine to the infant, added to oral zidovudine prophylaxis starting at 28 weeks' gestation, is highly
effective in reducing mother-to-child transmission of HIV.
Loutfy, M. R. and S. L. Walmsley. 2004. "Treatment of HIV infection in pregnant women:
antiretroviral management options." Drugs, 64(5):471-88.
Increasing rates of HIV infection in women worldwide, especially among those of childbearing age, reinforce
the importance of understanding the management of HIV in pregnancy. Over the past decade, significant
advances have been made in the prevention of vertical HIV transmission, including the use of single and
combination antiretroviral therapy, elective caesarean section as the preferred mode of delivery and the
elimination of breast feeding. Multiple clinical trials assessing antiretroviral therapy in pregnancy have been
carried out worldwide. The first pivotal clinical trial, the AIDS Clinical Trials Group (ACTG) 076 study, was
conducted in 1994 using a three-part zidovudine regimen. Despite the success of this regimen at decreasing
rates of vertical transmission, it is not affordable in many developing countries. Consequently, many
international clinical trials have concentrated on short-course antiretroviral regimens including zidovudine
alone, zidovudine and lamivudine, and nevirapine alone. In the developed world, the management of
nonpregnant HIV-infected individuals has also undergone significant advances and has implications for the
management of HIV in pregnancy. A number of countries have participated in the development of guidelines
for the management of HIV in pregnancy, which recommend that HIV-infected pregnant women should be
offered combination antiretroviral therapy based on viral load and CD4+ cell count cut-offs used for
individuals who are not pregnant, preferably with the inclusion of zidovudine. However, to maximise the
benefits to their offspring, therapy is recommended at lower viral load thresholds than for nonpregnant
adults. For antiretroviral-naive women, therapy is deferred until the second trimester because of the potential
and uncertain risk of teratogenesis and the low risk of transmission during this period. Research has also
found that maternal factors including viral load, immune status, chorioamnionitis, prematurely ruptured
membranes and, to a lesser extent, intravenous drug use and smoking are associated with increased
vertical transmission. These represent potentially modifiable risk factors that should be addressed before
and throughout pregnancy. Despite the benefits of antiretroviral therapy to reduce HIV vertical transmission,
its use can be complicated by known and unknown risks of toxicity to the mother, fetus or both as well as
carrying the risk of developing drug-resistant virus. The latter can potentially compromise future treatment
options for both the mother and child. Other important challenges include the use of antiretroviral drugs
during pregnancy when the mother does not meet criteria for them for her own health, and balancing the
relative risks and benefits of elective caesarean section at various degrees of viral load suppression.
Clinicians managing HIV in pregnancy need to keep up to date with all the literature to provide optimal care,
including counselling to allow mothers to balance the risks and benefits while deciding on treatment for both
themselves and their children.
Milinkovic, A. and E. Martinez. 2004. "Nevirapine in the treatment of HIV." Expert Rev
Anti Infect Ther, 2(3):367-73.
Nevirapine (Viramune, Boehringer Ingelheim Ltd) is the first marketed non-nucleoside reverse transcriptase
inhibitor. As with any antiretroviral drug, nevirapine should always be used as part of a fully suppressive
regimen. Clinical studies have shown that nevirapine-containing regimens may accomplish durable
virological and immunological responses in approximately half of all antiretroviral-naive patients. It can also
Page 23 of 56
be successfully used as a component of salvage therapies and as a part of a strategy to simplify protease
inhibitor-containing regimens. Nevirapine has a beneficial effect on the lipid profile in both treatment-naive
and -experienced patients. Nevirapine also has an important role in preventing mother-to-child transmission
of HIV. It is usually well-tolerated with rash and liver toxicity being the most frequently reported adverse
events. Nevirapine interacts with cytochrome P450 enzymes both as a substrate and as an inducer. For this
reason, therapeutic drug monitoring should be recommended whenever nevirapine is used with protease
inhibitors, methadone (Methadose, Rosemont Pharmaceuticals Ltd), oral contraceptives, rifampicin (Rifadin,
Aventis Pharma) and other potentially interacting drugs. Nevirapine-resistant mutations are common to the
non-nucleoside reverse transcriptase inhibitor family and they include K103N, V106A, Y181C, Y188C and
G190A. A better understanding of the nevirapine profile will certainly contribute to ensuring that its clinical
application becomes more effective and beneficial.
Mirochnick, M. and E. Capparelli. 2004. "Pharmacokinetics of antiretrovirals in pregnant
women." Clin Pharmacokinet, 43(15):1071-87.
Antiretroviral treatment of HIV-infected pregnant women is widely used to prevent mother-to-child HIV
transmission and as primary therapy of maternal HIV infection. The physiological changes associated with
pregnancy have a large impact on drug disposition, and changes in antiretroviral pharmacokinetics during
pregnancy must be understood for these drugs to be used safely and effectively in pregnant women.
Zidovudine and didanosine, two of the nucleoside reverse transcriptase inhibitors, demonstrate an increase
in clearance and decrease in area under the concentration-time curve during pregnancy. The clinical
significance of these changes is unknown due to the lack of a clear relationship between plasma
concentrations of nucleoside reverse transcriptase inhibitors and clinical effects. Pharmacokinetic
parameters of lamivudine, stavudine and abacavir are not significantly changed during pregnancy. There are
no data describing the effect of pregnancy on the pharmacokinetics of the other nucleoside/nucleotide
analogues (zalcitabine, emtricitabine and tenofovir). Pregnancy does not appear to have a significant effect
on the pharmacokinetics of the non-nucleoside reverse transcriptase inhibitor nevirapine and there are no
data describing the pharmacokinetics of the other non-nucleoside reverse transcriptase inhibitors (efavirenz
and delavirdine) during pregnancy. Reduced plasma concentrations during pregnancy have been described
for several of the protease inhibitors, including nelfinavir (with administration of 750 mg three times daily),
indinavir, saquinavir and Kaletra (a co-formulation of lopinavir and ritonavir). Plasma concentrations
equivalent to those in nonpregnant adults have been reported in pregnant women receiving nelfinavir at
doses of 1250 mg twice daily, and the addition of ritonavir to saquinavir greatly increases saquinavir
exposure to therapeutic concentrations in pregnant women. No pregnancy pharmacokinetic data are
available for the newer protease inhibitors atazanavir and fosamprenavir, or with other dual protease
inhibitor combinations that include low dose ritonavir to boost concentrations of the coadministered protease
inhibitor. Further investigations of antiretroviral pharmacology during pregnancy, including protein binding
studies, are urgently needed.
Musoke, P. 2004. "Recent advances in prevention of mother to child (PMTCT) of HIV."
Afr Health Sci, 4(3):144-5.
Mwapasa, V., S. J. Rogerson, M. E. Molyneux, E. T. Abrams, D. D. Kamwendo, V. M.
Lema, E. Tadesse, E. Chaluluka, P. E. Wilson, and S. R. Meshnick. 2004. "The
effect of Plasmodium falciparum malaria on peripheral and placental HIV-1 RNA
concentrations in pregnant Malawian women." Aids, 18(7):1051-9.
OBJECTIVE: To investigate the effect of placental Plasmodium falciparum malaria infection on peripheral
and/or placental HIV-1 viral load. DESIGN: A cross-sectional study of HIV-infected pregnant women, with
and without placental malaria, delivering at Queen Elizabeth Central Hospital in Malawi. METHODS:
Peripheral blood samples were collected from consenting women and tested for HIV. HIV-infected women
received nevirapine at the onset of labor. At delivery, placental blood and tissue specimens were collected.
HIV-1 RNA concentrations were measured in peripheral and placental plasma samples, and malaria
infection was determined by placental histopathology. RESULTS: Of the 480 HIV-infected women enrolled,
304 had placental histopathology performed, of whom 74 (24.3%) had placental malaria. Compared with
women without placental malaria, those with placental malaria had a 2.5-fold higher geometric mean
peripheral HIV-1 RNA concentration (62,359 versus 24 814 copies/ml; P = 0.0007) and a 2.4-fold higher
Page 24 of 56
geometric mean placental HIV-1 RNA concentration (11,733 versus 4919 copies/ml; P = 0.008). In
multivariate analyses, after adjusting for CD4 cell count and other covariates, placental malaria was
associated with a 1.7-fold increase in geometric mean peripheral HIV-1 RNA concentration (47,747 versus
27,317 copies/ml; P = 0.02) and a 2.0-fold increase in geometric mean placental HIV-1 RNA concentration
(9670 versus 4874 copies/ml; P = 0.03). CONCLUSION: Placental malaria infection is associated with an
increase in peripheral and placental HIV-1 viral load, which might increase the risk of mother-to-child
transmission of HIV.
Perez, F., T. Mukotekwa, A. Miller, J. Orne-Gliemann, M. Glenshaw, I. Chitsike, and F.
Dabis. 2004. "Implementing a rural programme of prevention of mother-to-child
transmission of HIV in Zimbabwe: first 18 months of experience." Trop Med Int
Health, 9(7):774-83.
OBJECTIVE: To report on activities and lessons learned during the first 18 months of a rural programme of
prevention of mother-to-child transmission of HIV (PMTCT) in Zimbabwe. METHODS: The PMTCT services
were introduced in Murambinda Mission Hospital (120 beds), Buhera, in 2001. Programme strategies
consisted in recruiting counselling staff, training health professionals, improving mother-child health (MCH)
facilities and conducting information, education and communication activities within the community to
address HIV/AIDS awareness and stigma. The following components were implemented within MCH
services: voluntary counselling and testing of HIV using rapid testing, nevirapine short regimen proposed to
all HIV-infected mothers identified and their newborns, support to exclusive breastfeeding for 6- and 18month mother-child follow-up. Routine monitoring data collected from August 2001 to February 2003 were
used to estimate programme uptake. RESULTS: Of 2471 pregnant women using antenatal services, 2298
were pre-test counselled, the acceptance of HIV testing reached 92.9%. Of the women who decided to take
an HIV test, 1588 (74.3%) returned to collect their result. Overall HIV prevalence was 20.4% (n = 437); 326
of the HIV-positive women were counselled and 104 (24%) received complete mother-child antiretroviral
prophylaxis. CONCLUSIONS: Acceptability of HIV testing after counselling has remained above 90% since
the onset of the programme. Collection of test results and mother-child follow-up are among the most
challenging activities of the programme. A district approach and community participation are critical to
develop PMTCT programmes in rural settings, even with reasonably good MCH services.
Perez, F., J. Orne-Gliemann, T. Mukotekwa, A. Miller, M. Glenshaw, A. Mahomva, and
F. Dabis. 2004. "Prevention of mother to child transmission of HIV: evaluation of
a pilot programme in a district hospital in rural Zimbabwe." Bmj, 329(7475):114750.
PROBLEM: Zimbabwe has one of the highest rates of HIV seroprevalence in the world. In 2001 only 4% of
women and children in need of services for prevention of mother to child transmission of HIV were receiving
them. DESIGN: Pilot implementation of the first programme for prevention of mother to child transmission of
HIV in rural Zimbabwe. SETTING: 120 bed district hospital in Buhera district (285,000 inhabitants),
Manicaland, Zimbabwe. KEY MEASURES FOR IMPROVEMENT: Programme uptake indicators monitored
for 18 months; impact of policy evaluated by assessing up-scaling of programme. STRATEGIES FOR
CHANGE: Voluntary counselling and testing services for HIV were provided in the hospital antenatal clinic.
Women identified as HIV positive and informed of their serostatus and their newborn were offered a single
dose antiretroviral treatment of nevirapine; mother-child pairs were followed up through routine health
services. Nursing staff and social workers were trained, and community mobilisation was conducted.
EFFECTS OF CHANGE: No services for prevention of mother to child transmission of HIV were available at
baseline. Within 18 months, 2298 pregnant women had received pretest counselling, and the acceptance of
HIV testing reached 93.0%. Of all 2137 women who had an HIV test, 1588 (74.3%) returned to collect their
result; 326 of the 437 HIV positive women diagnosed had post-test counselling, and 104 (24%) mother-child
pairs received nevirapine prophylaxis. LESSONS LEARNT: Minimum staffing, an enhanced training
programme, and involvement of district health authorities are needed for the implementation and successful
integration of services for prevention of mother to child transmission of HIV. Voluntary counselling and
testing services are important entry points for HIV prevention and care and for referral to community
networks and medical HIV care services. A district approach is critical to extend programmes for prevention
of mother to child transmission of HIV in rural settings. The lessons learnt from this pilot programme have
contributed to the design of the national expansion strategy for prevention of mother to child transmission of
HIV in Zimbabwe.
Page 25 of 56
Quaghebeur, A., L. Mutunga, F. Mwanyumba, K. Mandaliya, C. Verhofstede, and M.
Temmerman. 2004. "Low efficacy of nevirapine (HIVNET012) in preventing
perinatal HIV-1 transmission in a real-life situation." Aids, 18(13):1854-6.
Since 2001, the unrestricted use of HIVNET012 has been recommended for the prevention of mother-tochild transmission in low-resource settings, despite the lack of validated efficacy data outside research
settings. We implemented the nevirapine regimen in a real-life situation in Kenya. The perinatal HIV-1
transmission rate at 14 weeks was 18.1%, similar to the 21.7% before the intervention. These data call for
further evaluation of the simple nevirapine regimen in field conditions, and underline the need for alter-native
strategies.
Servais, J., C. Lambert, E. Karita, D. Vanhove, A. Fischer, T. Baurith, J. C. Schmit, F.
Schneider, R. Hemmer, and V. Arendt. 2004. "HIV type 1 pol gene diversity and
archived nevirapine resistance mutation in pregnant women in Rwanda." AIDS
Res Hum Retroviruses, 20(3):279-83.
This study aimed to find out whether genetic polymorphisms were present in positions potentially affecting
susceptibility to antiretrovirals in non-B subtypes from HIV-1-infected patients in Rwanda. Viral pol gene
diversity was investigated by direct sequencing in 43 treatment-naive women. In addition, 10 DNA
sequences from uncultured peripheral blood mononuclear cells were analyzed 6 weeks after a single dose
of nevirapine (prevention of mother-to-child transmission program). Phylogenetic analyses have shown 34
subtype A1, 6 subtype C, and 2 subtype D strains. In addition, an A/C recombinant between the protease
(PR) (subtype A1) and the reverse transcriptase (RT) (subtype C) was identified. In the PR coding region,
high numbers of polymorphisms were found, including substitutions in secondary PR resistance sites. PR
35D, 36I, and 37N were always present within subtype A as were PR 93L in subtype C strains. PR 10I/V,
20R, 33F, and 77V were found in subtype A whereas PR 36I was highly prevalent in subtype C strains. The
A/C recombinant displayed substitutions related to resistance (PR 10, 33, 36 and RT 118). One nevirapine
resistance mutation (RT 181Y/C) was found in proviral DNA after 6 weeks. In conclusion, subtypes A and C
are predominant in this cohort in Rwanda. Substitutions similar to secondary protease inhibitor resistance
mutations are common before treatment whereas major resistance mutation may be archived after a single
dose of nevirapine. Accordingly, the hypothesis of a genetic background effect in non-B strains has to be
further addressed in programs of introduction of antivirals in Africa.
Sherman, G. G., S. A. Jones, A. H. Coovadia, M. F. Urban, and K. D. Bolton. 2004.
"PMTCT from research to reality--results from a routine service." S Afr Med J,
94(4):289-92.
OBJECTIVES: Assessment of the efficacy of a prevention of mother-to-child transmission (PMTCT)
programme in a routine service setting in comparison to a research environment. DESIGN: Descriptive study
over a 13-month period utilising retrospective data obtained from hospital records complemented by
prospective data on a sample of patients enrolled in a study to determine an affordable HIV diagnostic
protocol for infants. SETTING: Routine PMTCT service at Coronation Women and Children's Hospital
(CWCH) situated in Johannesburg and affiliated to the University of the Witwatersrand. SUBJECTS:
Pregnant women known to be HIV infected who delivered at CWCH from 1 October 2001 to 31 October
2002. OUTCOME MEASURES: The HIV transmission rate to infants, which reflects nevirapine (NVP)
delivery and infant feeding practices, and follow-up rates of perinatally exposed children. RESULTS: Of the
8,221 deliveries, 1,234 (15%) occurred in women known to be HIV infected. HIV transmission rates of 8.7%
at 6 weeks and 8.9% at 3 months of age in the study population verifies the high rate of NVP administration
and the ability of women to formula-feed their babies and abstain from breast-feeding. More than one-third
of infants never return for follow-up and more than 70% are lost to follow-up by 4 months of age.
CONCLUSIONS: The low HIV transmission rate confirms the efficacy of this routine service PMTCT
programme. HIV-infected children are not being identified for medical management as part of PMTCT followup. It is imperative that record keeping is improved to facilitate ongoing monitoring.
Page 26 of 56
Smart, T. 2004. "Mother-to-child transmission. How will AZT and nevirapine use for
MTCT affect future treatment? Two studies provide clues." Beta, 16(2):32-3.
Steel-Duncan, J. C., R. Pierre, T. Evans-Gilbert, B. Rodriquez, M. F. Smikle, P. Palmer,
S. Whorms, I. Hambleton, J. P. Figueroa, and C. D. Christie. 2004. "Uptake of
interventions, outcomes and challenges in caring for HIV-exposed infants in
Kingston, Jamaica." West Indian Med J, 53(5):308-14.
BACKGROUND: In a few Caribbean islands, prevention of mother-to-child transmission (pMTCT) of HIV
with zidovudine prophylaxis has reduced transmission rates from 27 - 44% to 5.5 - 9 %. OBJECTIVES: To
highlight the uptake of interventions, preliminary outcomes and challenges in caring for HIV-exposed infants
in a pMTCT HIVprogramme in a resource-limited setting. METHOD: A cohort of HIV-infected pregnant
women were identified at the leading maternity centres in Greater Kingston through HIV counselling and
testing and enrolled in the Kingston Paediatric and Perinatal HIV/AIDS Programme. Antiretroviralprophylaxis
with zidovudine or nevirapine was given to the HIV-positive women and their newborns along with formula
feeding. Some infants were enrolled retrospectively and followed irrespective of whether they had or had not
received antiretroviral prophylaxis. A multidisciplinary team at the paediatric centres supervised protocoldriven management of the infants. Infants were followed for clinical progress and definitive HIV-infection
status was to be confirmed at 18 months of age by ELISA or the Determine Rapid Test. RESULTS: During
September 1, 2002 through August 31, 2003, 132 HIV-exposed infants were identified. For those infants
prospectively enrolled (78), 97% received antiretroviral prophylaxis and 90% were not breastfed For all HIVexposed children, 90% received cotrimoxazole prophylaxis and 88% continued follow-up care. Ninety-two
per cent of all the infants remained asymptomatic and five died; of these deaths one is possibly HIV-related
(severe sepsis at 11 weeks). This infant was retrospectively identified, had received no antiretroviral
prophylaxis and was breastfed The main programme challenges, which were overcome, included the impact
of stigma, compliance with antiretroviral chemoprophylaxis, breast-milk substitution and follow-up care.
Financial constraints and laboratory quality assurance issues limited early diagnosis of HIV infection.
CONCLUSION: Despite the challenges, the expected outcome is to prevent 50 new cases of HIV/AIDS in
children living in Greater Kingston per year (300 over six years).
Steel-Duncan, J. C., R. Pierre, L. Gabay, and C. D. Christie. 2004. "Nevirapineassociated rash in a Jamaican child with HIV/AIDS." West Indian Med J,
53(5):356-8.
Nevirapine is one of the first line antiretroviral agents used in the treatment of HIV/AIDS as well as for
prophylaxis against mother-to-child transmission of HIV As antiretroviral medication becomes more available
it is important for physicians to recognize the major clinical toxicities of these medications. We report a HIVinfected infant who developed a rash with systemic symptoms in association with nevirapine administration.
Stringer, J. S., M. Sinkala, R. L. Goldenberg, R. Kumwenda, E. P. Acosta, G. M.
Aldrovandi, J. P. Stout, and S. H. Vermund. 2004. "Universal nevirapine upon
presentation in labor to prevent mother-to-child HIV transmission in high
prevalence settings." Aids, 18(6):939-43.
OBJECTIVE: To assess the uptake of and adherence to nevirapine to prevent mother-to-child HIV
transmission among women of unknown HIV serostatus presenting in labor. We also assessed preliminary
efficacy of the approach. DESIGN: Women of unknown HIV serostatus presenting in labor were offered
single-dose nevirapine in a prospective cohort study. Two additional contemporaneous comparison
populations were also studied. METHODS: We measured uptake by counting the number of women that
accepted enrollment when offered. We measured adherence with cord blood nevirapine assay. We
measured preliminary efficacy with HIV DNA polymerase chain reaction of infant blood spots at 4-6 weeks of
life. RESULTS: Of 1591 women approached in labor, 634 (40%) took up the intervention and received
nevirapine, of whom 185 (29%) were HIV infected. Of 179 cord blood specimens from HIV-exposed infants
that could be evaluated, 178 (99.4%) had nevirapine detected. This was higher than the 73 of 98 (74%)
adherence rate observed in a comparison cohort in which women self-administered nevirapine before
Page 27 of 56
presenting to the labor ward (P < 0.001). Of 145 available infant specimens, 17 (11.7%) showed evidence of
infection at 4-6 weeks, compared with 12 of 60 (20%) infants born immediately prior to study
commencement whose HIV-infected mothers did not receive nevirapine (P < 0.05). CONCLUSIONS:
Nevirapine without HIV testing upon presentation in labor was accepted by two-fifths of women. Because
therapy is directly observed, adherence is nearly perfect. Labor ward dosing to enhance nevirapine
coverage should be considered as an adjunct to antenatal nevirapine administration for prevention of
mother-to-child transmission of HIV.
Sweat, M. D., K. R. O'Reilly, G. P. Schmid, J. Denison, and I. de Zoysa. 2004. "Costeffectiveness of nevirapine to prevent mother-to-child HIV transmission in eight
African countries." Aids, 18(12):1661-71.
BACKGROUND: A comprehensive approach to preventing HIV infection in infants has been recommended,
including: (a) preventing HIV in young women, (b) reducing unintended pregnancies among HIV-infected
women, (c) preventing vertical transmission (PMTCT), and (d) providing care, treatment, and support to HIVinfected women and their families. Most attention has been given to preventing vertical transmission based
on analysis showing nevirapine to be inexpensive and cost-effective. METHODS: The following were
determined using data from eight African countries: national program costs and impact on infant infections;
reductions in adult HIV prevalence and unintended pregnancies among HIV-infected women that would
have equivalent impact on infant HIV infections averted as the nevirapine intervention; and the cost
threshold for drugs with greater efficacy than nevirapine yielding an equivalent cost per DALY saved.
RESULTS: Average national annual program cost was 4.8 million dollars. There was, per country, an
average of 1898 averted infant HIV infections (2517 US dollars per HIV infection and 84 US dollars per
DALY averted). Lowering HIV prevalence among women by 1.25% or reducing unintended pregnancy
among HIV-infected women by 16% yielded an equivalent reduction in infant cases. An antiretroviral drug
with 70% efficacy could cost 152 US dollars and have the same cost per DALY averted as nevirapine at
47% efficacy. CONCLUSIONS: Cost-effectiveness of nevirapine prophylaxis is influenced by health system
costs, low client uptake, and poor effectiveness of nevirapine. Small reductions in maternal HIV prevalence
or unintended pregnancy by HIV-infected women have equivalent impacts on infant HIV incidence and
should be part of an overall strategy to lessen numbers of infant infections.
Taha, T. E., N. Kumwenda, G. Kafulafula, J. Kumwenda, R. Chitale, C. Nkhoma, P.
Katundu, J. Mukiibi, S. Chen, D. Hoover, and R. Broadhead. 2004.
"Haematological changes in African children who received short-term prophylaxis
with nevirapine and zidovudine at birth." Ann Trop Paediatr, 24(4):301-9.
We assessed the safety of short-term antiretroviral prophylaxis to prevent mother-to-child transmission
(MTCT) of HIV by monitoring haematological changes in children up to the age of 18 months. Babies of HIVinfected women were randomised at birth to receive a single dose of nevirapine (NVP) alone or with
zidovudine (ZDV) twice daily for a week. Based on the time of presentation to the labour ward, mothers of
these babies might or might not have received intrapartum NVP. Complete blood counts were performed at
birth and at 1.5, 3, 6, 9, 12, 15 and 18 months. Babies' HIV status was determined by HIV-1 RNA testing. A
total of 1755 babies were included in the study. Age-specific mean haemoglobin levels and prevalence of
anaemia (haemoglobin < 10 g/dL) were not significantly different in cases where only the babies received a
single dose of NVP and cases where NVP was given to mother/infant pairs or additional ZDV to the baby.
Among HIV-infected children compared with uninfected children, the age-specific frequency of anaemia was
significantly greater, anaemia started earlier and recovery to normal levels was slower and prolonged. A
reversible granulocytopenia was observed in all children between 1.5 and 3 months of age. HIV infection
significantly increased the children's risk of death. Antiretroviral prophylaxis appeared to protect against
anaemia and child death. Short regimens of antiretrovirals to prevent MTCT of HIV are not associated with
long-term adverse haematological changes.
Taha, T. E., N. I. Kumwenda, D. R. Hoover, S. A. Fiscus, G. Kafulafula, C. Nkhoma, S.
Nour, S. Chen, G. Liomba, P. G. Miotti, and R. L. Broadhead. 2004. "Nevirapine
and zidovudine at birth to reduce perinatal transmission of HIV in an African
setting: a randomized controlled trial." Jama, 292(2):202-9.
Page 28 of 56
CONTEXT: Antenatal counseling and human immunodeficiency virus (HIV) testing are not universal in
Africa; thus, women often present in labor with unknown HIV status without receiving the HIVNET 012
nevirapine (NVP) regimen (a single oral dose of NVP to the mother at the start of labor and to the infant
within 72 hours of birth). OBJECTIVE: To determine risk of mother-to-child transmission of HIV when either
standard use of NVP alone or in combination with zidovudine (ZDV) was administered to infants of women
tested at delivery. DESIGN, SETTING, AND PARTICIPANTS: A randomized, open-label, phase 3 trial
conducted between April 1, 2000, and March 15, 2003, at 6 clinics in Blantyre, Malawi, Africa. The trial
included all infants born to 894 women who were HIV positive, received NVP intrapartum, and were
previously antiretroviral treatment-naive. Infants were randomly assigned to NVP (n = 448) and NVP plus
ZDV (n = 446). Infants were enrolled at birth, observed at 6 to 8 weeks, and followed up through 3 to 18
months. The HIV status of 90% of all infants was established at 6 to 8 weeks. INTERVENTION: Mothers
received a 200-mg single oral dose of NVP intrapartum and infants received either 2-mg/kg oral dose of
NVP or NVP (same dose) plus 4 mg/kg of ZDV twice per day for a week. MAIN OUTCOME MEASURES:
HIV infection of infant at birth and 6 to 8 weeks, and adverse events. RESULTS: The mother-to-child
transmission of HIV at birth was 8.1% (36/445) in infants administered NVP only and 10.1% (45/444) in
those administered NVP plus ZDV (P =.30). A life table estimate of transmission at 6 to 8 weeks was 14.1%
(95% confidence interval [CI], 10.7%-17.4%) in infants who received NVP and 16.3% (95% CI, 12.7%19.8%) in those who received NVP plus ZDV (P =.36). For infants not infected at birth and retested at 6 to 8
weeks, transmission was 6.5% (23/353) in those who received NVP only and 6.9% (25/363) in those who
received NVP plus ZDV (P =.88). Almost all infants (99%-100%) were breastfed at 1 week and 6 to 8 weeks.
Grades 3 and 4 adverse events were comparable; 4.9% (22/448) and 5.4% (24/446) in infants receiving
NVP only and NVP plus ZDV, respectively (P =.76). CONCLUSIONS: The frequency of mother-to-child HIV
transmission at 6 to 8 weeks in our 2 study groups was comparable with that observed for other perinatal
HIV intervention studies among breastfeeding women in Africa. The safety of the regimen containing
neonatal ZDV was similar to that of a standard NVP regimen.
Tarwireyi, F. 2004. "Implementation of the prevention of mother-to-child transmission of
HIV programme in Zimbabwe: achievements and challenges." Cent Afr J Med,
50(9-10):95-100.
Recent scientific developments have led to feasible and effective interventions to reduce the risk of mother
to child transmission of HIV. Even in resource poor countries, PMTCT programmes are being articulated as
a priority in the national strategic frameworks. Thus PMTCT programmes are moving from being pilot
projects to national programmes comprehensively integrated into other reproductive health programmes or
HIV and AIDS prevention, care and support programmes. In Zimbabwe the prevention of mother-to-child
transmission (PMTCT) of HIV infection has become an important national task. The 2001 national survey of
HIV prevalence among women attending antenatal care revealed that 29.5% of the women were HIV
positive. While an effective PMTCT programme using nevirapine can reduce the rate of this transmission by
50%, the Zimbabwe PMTCT National Expansion Programme has had its share of achievements and
challenges since its launch in 2002.
Thea, D. M., C. Vwalika, P. Kasonde, C. Kankasa, M. Sinkala, K. Semrau, E. Shutes, C.
Ayash, W. Y. Tsai, G. Aldrovandi, and L. Kuhn. 2004. "Issues in the design of a
clinical trial with a behavioral intervention--the Zambia exclusive breast-feeding
study." Control Clin Trials, 25(4):353-65.
PURPOSE: We present the rationale and design of the Zambian Exclusive Breast-feeding Study (ZEBS), a
randomized trial evaluating the efficacy of short-duration exclusive breast-feeding (EBF) as a strategy to
reduce postnatal human immunodeficiency virus (HIV) transmission while preserving the other health
benefits of this important mode of infant feeding. METHODS: One thousand two hundred HIV-positive
pregnant women were recruited in Lusaka, Zambia, and followed with their infants for 24 months. In addition
to Nevirapine (NVP), all women received intensive and frequent clinic- and home-based counseling to
support exclusive breast-feeding. When the infant was 1 week of age, half of the women were randomly
assigned to a group encouraged to abruptly (<24 h) cease all breast-feeding at 4 months. The primary
outcome of the experimental (randomized) comparison is HIV-free survival at 24 months. The design is also
observational and will compare HIV transmission rates between those who do and do not adhere to the
counseling intervention promoting exclusive breast-feeding. CONCLUSION: Our study aims to quantify the
Page 29 of 56
benefit-risk ratio of early cessation of exclusive breast-feeding to interrupt mother-to-child transmission of
HIV with an intensive behavioral intervention and has both observational and experimental analytic
approaches. Our study design assesses efficacy and also has a prominent applied component that if the
intervention is effective, it will permit rapid and sustainable adoption within low-resource communities.
Tuaillon, E., M. Gueudin, V. Lemee, I. Gueit, P. Roques, G. E. Corrigan, J. C. Plantier,
F. Simon, and J. Braun. 2004. "Phenotypic susceptibility to nonnucleoside
inhibitors of virion-associated reverse transcriptase from different HIV types and
groups." J Acquir Immune Defic Syndr, 37(5):1543-9.
OBJECTIVES: To evaluate a phenotype assay based on plasma reverse transcriptase (RT) to assess HIV
susceptibility to nonnucleoside RT inhibitors (NNRTIs). To compare RT-based phenotype with recombinant
virus assay (RVA) phenotype- and genotype-based analysis. To assess group O and HIV-2 susceptibility to
NNRTIs in correlation with genotype polymorphisms. METHODS: RT activity was quantified and its
susceptibility to efavirenz, nevirapine, and delavirdine measured as drug concentration resulting in 50%
inhibition. RT phenotype was compared with genotype analysis. Eighteen plasma samples from 14 group Mand culture supernatants from 4 group M-, 9 group O-, and 7 HIV-2-infected patients were investigated. RTbased and RVA-based phenotypes were compared for identical plasma from 9 group M-infected patients.
RESULTS: RT-based and RVA-based phenotypes were in complete agreement. RT-based phenotype- and
genotype-predicted susceptibility were concordant for all but 1 group M samples. One plasma showed
susceptibility to 3 NNRTIs by phenotypes, despite the presence of 101E and 106I/V residues. The HIV-2
RTs were totally resistant to the NNRTIs tested. Among HIV-1 group O, 6 were totally resistant to NNRTIs
independently of the presence of the 181C mutation and 3 were susceptible to some NNRTIs.
CONCLUSION: Plasma RT-based phenotype could be useful as a simple alternative for monitoring
resistance to NNRTIs. This assay is suitable for highly divergent strains. It would be particularly useful for
large epidemiologic survey of the natural HIV polymorphism and the potential impact in emergence of drug
resistance, particularly to nevirapine, widely used to prevent mother-to-child transmission.
Urban, M. and M. Chersich. 2004. "Acceptability and utilisation of voluntary HIV testing
and nevirapine to reduce mother-to-child transmission of HIV-1 integrated into
routine clinical care." S Afr Med J, 94(5):362-6.
OBJECTIVES: Use of nevirapine for prevention of mother-to-child transmission (PMTCT) of HIV-1 has been
routine clinical care at Coronation Women and Children's Hospital since April 2000. We assessed the effect
of regular audit and targeted interventions on the utilisation of the PMTCT programme. METHODS: Review
of antenatal cards and hospital records of women discharged following delivery, in three time periods
between October 2000 and February 2002. Following the initial audit an intervention was implemented to
eliminate weaknesses in our PMTCT service. Following the second audit the hospital became a pilot site for
the Gauteng PMTCT programme. RESULTS: In the initial audit 53.2% of women (159/299) were tested for
HIV and received their results, while 56% (14/25) of identified HIV-infected women, and 16% (4/25) of their
infants, received nevirapine. By the third audit 74.3% of women (266/358) received their results, and 86%
(43/50) of HIV-positive women and 74% (37/50) of newborns were documented to have received nevirapine.
In all three audits over 90% of women initiating antenatal care at the hospital were tested for HIV, while
women who initiated care at district community clinics were less likely to receive testing. CONCLUSIONS:
Ongoing audit has been important for targeting obstacles to detection of HIV-infected women and
documented nevirapine uptake by women and infants. Rates of HIV testing and nevirapine use have
increased significantly. Voluntary counselling and testing for HIV and use of nevirapine are acceptable to
pregnant women in our setting. Roll-out of the pilot programme to district community clinics is essential for
further improvement.
Vermund, S. H. 2004. "Prevention of mother-to-child transmission of HIV in Africa." Top
HIV Med, 12(5):130-4.
HIV infection and mortality rates in African children are astoundingly high. Risk factors for mother-to-child
transmission of HIV include maternal plasma viral load and breastfeeding. With regard to the latter, current
data indicate that mixed feeding (breastfeeding with other oral foods and liquids) is associated with the
greatest risk of transmission. Studies are under way to determine if exclusive breastfeeding with rapid early
Page 30 of 56
weaning can reduce transmission rates in the absence of exclusive formula feeding for all infants. Perinatal
transmission rates have been dramatically reduced with the use of single-dose nevirapine, but this strategy
protects only approximately 50% of infants, and more than 75% of women receiving nevirapine develop a
major nevirapine resistance mutation. In developed areas of the world, antiretroviral therapy has reduced
perinatal transmission by more than 90% compared with 1993 rates. Improved HIV-related care for HIVinfected women in Africa is needed to reduce rates of HIV infection in children and to prevent maternal
mortality. This article summarizes a presentation by Sten H. Vermund, MD, PhD, at the International AIDS
Society-USA course in Chicago in May 2004.
2003. "Nevirapine reduced mother-to-child transmission better than AZT--at 70 times
less the cost." AIDS Treat News, (394):7.
A follow-up of a Uganda study shows that a single dose of nevirapine to the mother in labor and a single
dose to the infant shortly after birth continues to show excellent results when the infants reach 18 months-despite breast feeding for 99% of the infants, and some HIV transmission that occurred as a result.
Ayouba, A., E. Nerrienet, E. Menu, M. M. Lobe, J. Thonnon, R. J. Leke, F. BarreSinoussi, P. Martin, and P. Cunin. 2003. "Mother-to-child transmission of human
immunodeficiency virus type 1 in relation to the season in Yaounde, Cameroon."
Am J Trop Med Hyg, 69(4):447-9.
A public health program to prevent mother-to-child transmission (MTCT) of human immunodeficiency virus
type 1 (HIV-1) by treatment with nevirapine has been ongoing in Yaounde, Cameroon since January 2000.
After 24 months, plasma samples from 119 children born to HIV-1-positive mothers were tested for HIV-1
RNA between six and eight weeks after birth. Thirteen (10.9%) tested positive (95% confidence interval =
5.2-16.7%). Risk factors associated with MTCT in this study were maternal viral load (P < 0.05), low birth
weight (chi2 for trend = 8.78, P = 0.01), and birth during the second half of the year. A high correlation was
repeatedly observed between rainfall in a given month and the risk of MTCT of HIV-1 in children born three
months later (r = 0.634, P < 0.001). Although we cannot rule out other tropical infections related to the rainy
season, the role of malaria is highly suspected since the interval of three months we observed between the
peaks of rainfall and the rate of transmission is consistent with the Plasmodium life cycle.
Ayouba, A., G. Tene, P. Cunin, Y. Foupouapouognigni, E. Menu, A. Kfutwah, J.
Thonnon, G. Scarlatti, M. Monny-Lobe, N. Eteki, C. Kouanfack, M. Tardy, R.
Leke, M. Nkam, A. E. Nlend, F. Barre-Sinoussi, P. M. Martin, and E. Nerrienet.
2003. "Low rate of mother-to-child transmission of HIV-1 after nevirapine
intervention in a pilot public health program in Yaounde, Cameroon." J Acquir
Immune Defic Syndr, 34(3):274-80.
OBJECTIVE: To determine the percentage of infected children for whom nevirapine (NVP) was used to
prevent peripartum mother-to-child transmission (MTCT) of HIV in Yaounde, Cameroon. DESIGN: The study
was a prospective Public Health Pilot Program covering a 3-year period (January 2000-December 2002).
METHODS: Counseled and consenting HIV-1-positive pregnant women were given a single dose of NVP at
the onset of labor. Babies were given 2 mg/kg NVP syrup within the first 72 hours of life. NVP-treated
children were regularly followed up and examined for HIV-1 infection at 6-8 weeks and 5-6 months through
plasma viral load (VL) quantification with the bDNA system. RESULTS: One hundred twenty-three children
were diagnosed with perinatal HIV-1 infection at 6-8 weeks and 5-6 months. Thirteen children (10.6%
[13/123]; 95% confidence interval, 5.1-16) were infected and presented with high VLs, in general >500,000
copies/mL. Two children had intermediate VLs (between 50 and 3500 copies/mL) at both time points. One
hundred seven children (87%) were considered not infected at 6-8 weeks of age. CONCLUSIONS: Our
results indicate that the HIV-1 MTCT rate 6-8 weeks after NVP administration was not >13% (16/123), thus
demonstrating the effectiveness of NVP for lowering the risk of HIV-1 MTCT in real-life settings.
Page 31 of 56
Bertolli, J., D. J. Hu, P. Nieburg, A. Macalalad, and R. J. Simonds. 2003. "Decision
analysis to guide choice of interventions to reduce mother-to-child transmission
of HIV." Aids, 17(14):2089-98.
INTRODUCTION: Antiretroviral prophylaxis, avoidance of breastfeeding, and early weaning are candidates
to prevent mother-to-child transmission (MTCT) of HIV worldwide. METHODS: We developed a model to
help guide population-level decisions about MTCT intervention strategies. We estimated the numbers of
early childhood deaths prevented by (1) prenatal short-course zidovudine, (2) intrapartum and neonatal
short-course nevirapine, (3) avoidance of breastfeeding, and (4) early weaning (age 6 months); four
combinations of these; and one possible future strategy (postnatal antiretroviral prophylaxis) in a scenario
typical of a developing country. We evaluated the effectiveness of the interventions for a range of R, the
relative risk of mortality for children exposed to breastfeeding interventions compared with breastfed children
(independent of HIV infection). We also estimated the reduction in breastfeeding transmission needed for a
postnatal antiretroviral intervention to prevent more early childhood deaths than do currently available
interventions. RESULTS: Where R < or = 1.5, strategies combining antiretroviral prophylaxis with
breastfeeding interventions prevent the most early childhood deaths. However, strategies that include early
weaning and avoidance of breastfeeding, respectively, can result in more deaths than with no intervention
when R > 1.5 and R > 1.9, respectively. The relative effectiveness of a postnatal antiretroviral intervention
compared with avoidance of breastfeeding varies with R; such that an intervention would be more effective
than early weaning as a single intervention, at any R, if it reduced HIV transmission through breastfeeding
by 25%. CONCLUSION: This spreadsheet model is a simple, locally adaptable tool to allow decision-makers
to explore key questions about intervention strategies to prevent MTCT of HIV.
Bruun, J. N. 2003. "[Antiviral agents for reduction of mother-to-child transmission of HIV
infection]." Tidsskr Nor Laegeforen, 123(15):2041-2.
Fiore, S., C. Thorne, and M. L. Newell. 2003. "European participation in an international
perinatal trial." Med Wieku Rozwoj, 7(4 Pt 1):449-58.
OBJECTIVES: To identify factors affecting recruitment into a randomised trial involving HIV infected
pregnant women. To compare the population enrolled in a Phase III trial to that enrolled during the same
period in a parallel longitudinal cohort, and to assess the generalisability of the trial results. MATERIAL AND
METHODS: The PACTG 316 trial was initiated in the USA and subsequently extended to Europe. Based on
their involvement in an ongoing European cohort study, clinicians in 27 antenatal HIV reference centres in
Italy, Spain, Sweden, UK, Belgium, Germany, Switzerland, Netherlands and Denmark were asked to
participate. In centres with local, national and American approval, eligible women attending antenatal clinics
were offered the chance to take part in the trial, which aimed to evaluate the additional use of nevirapine
during labour and neonatally to reduce HIV mother-to-child transmission (MTCT). HIV-infected women who
did not enrol in the trial were enrolled in the European Collaborative Study (ECS). Reasons for nonrandomisation were recorded. Clinical and laboratory information on mother-child pairs were collected
according to a standard protocol. RESULTS: Between February 1999 and June 2000, 247 women were
enrolled in the ECS cohort and 118 were randomised in the 316 trial. Reasons for non-randomisation
included the presence of the placebo arm, randomisation procedures and delays in obtaining approval from
the various regulatory bodies. Women in the trial were younger, and their HIV disease was less advanced
than those included in the ECS. The MTCT rate in the ECS was higher than in the trial. CONCLUSIONS:
Differences between women who participated in the trial and those who did not had an effect on the
absolute vertical transmission rate, but not on the relative effectiveness of the intervention assessed within
the trial. Extrapolation of the trial MTCT rates to the general HIV infected population may be inappropriate.
Jackson, J. B., P. Musoke, T. Fleming, L. A. Guay, D. Bagenda, M. Allen, C. Nakabiito,
J. Sherman, P. Bakaki, M. Owor, C. Ducar, M. Deseyve, A. Mwatha, L. Emel, C.
Duefield, M. Mirochnick, M. G. Fowler, L. Mofenson, P. Miotti, M. Gigliotti, D.
Bray, and F. Mmiro. 2003. "Intrapartum and neonatal single-dose nevirapine
compared with zidovudine for prevention of mother-to-child transmission of HIV-1
Page 32 of 56
in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial."
Lancet, 362(9387):859-68.
BACKGROUND: In 1999, we reported safety and efficacy data for short-course nevirapine from a Ugandan
perinatal HIV-1 prevention trial when 496 babies were followed up to age 14-16 weeks. Safety and efficacy
data are now presented for all babies followed up to 18 months of age. METHODS: From November, 1997,
to April, 1999, HIV-1 infected pregnant women in Kampala, Uganda, were randomly assigned nevirapine
(200 mg at labour onset and 2mg/kg for babies within 72 h of birth; regimen A) or zidovudine (600 mg orally
at labour onset and 300 mg every 3 h until delivery, and 4 mg/kg orally twice daily for babies for 7 days,
regimenB). Infant HIV-1 testing was done at birth, age 6-8 and 14-16 weeks, and age 12 months by HIV-1
RNA PCR, and by HIV-1 antibody at 18 months. HIV-1 transmission and HIV-1-free survival were assessed
using Kaplan-Meier analysis. We recorded adverse experiences through 6-8 weeks postpartum for mothers,
and 18 months for babies. Efficacy analyses were by intention to treat. FINDINGS: We enrolled 645 mothers
to the study: 313 were assigned regimen A, 313 regimen B, and 19 placebo. Eight mothers were lost to
follow-up before delivery. 99% of babies were breastfed (median duration 9 months). Estimated risks of HIV1 transmission in the zidovudine and nevirapine groups were 10.3% and 8.1% at birth (p=0.35); 20.0% and
11.8% by age 6-8 weeks (p=0.0063); 22.1% and 13.5% by age 14-16 weeks (p=0.0064); and 25.8% and
15.7% by age 18 months (p=0.0023). Nevirapine was associated with a 41% (95% CI 16-59) reduction in
relative risk of transmission through to age 18 months. Both regimens were well-tolerated with few serious
side-effects. INTERPRETATION: Intrapartum/neonatal nevirapine significantly lowered HIV-1 transmission
risk in a breastfeeding population in Uganda compared with a short intrapartum/neonatal zidovudine
regimen. The absolute 8.2% reduction in transmission at 6-8 weeks was sustained at age 18 months (10.1%
[95% CI 3.5-16.6]). This simple, inexpensive, well-tolerated regimen has the potential to significantly
decrease HIV-1 perinatal transmission in less-developed countries.
Jaspan, H. B. and R. F. Garry. 2003. "Preventing neonatal HIV: a review." Curr HIV
Res, 1(3):321-7.
Mother-to-child transmission of human immunodeficiency virus type 1 has become rare in developed
countries, with the use of highly active antiretroviral treatment, elective cesarean section, and avoidance of
breastfeeding. In the developing world, however, these interventions are unfeasible, and cost-saving
methods for prevention of vertical transmission are vital. Prevention begins with voluntary counseling and
testing, improved maternal education and access to prenatal care. Various antiretroviral drugs administered
before, during, and for short periods after delivery have decreased vertical transmission. Where safe and
compliant formula feeding is difficult, avoidance of mixed feeding may improve infant outcomes. However,
post-natal transmission via breast milk remains a major challenge. As we continue to find cost-effective
answers to protect infants worldwide, the search for a HIV-1 vaccine continues.
Kapiriri, L., B. Robbestad, and O. Frithjof Norheim. 2003. "The relationship between
prevention of mother to child transmission of HIV and stakeholder decision
making in Uganda: implications for health policy." Health Policy, 66(2):199-211.
OBJECTIVES: To explore a selection of stakeholders' use of evidence and other reasons in the relative
ranking of the prevention of mother to child HIV transmission with nevirapine in a setting of extreme
resource scarcity. DESIGN: Group interviews using nominal group technique with provision of evidence.
SETTING: One rural and one urban district in Uganda. PARTICIPANTS: People living with HIV/AIDS,
people from the general population, planners, health workers and people with hypertension. MAIN
OUTCOME MEASURE: relative ranking of prevention of vertical HIV transmission with nevirapine compared
to nine other interventions for different conditions and evaluation of participants' use of evidence in the
ranking. RESULTS: In the overall final ranking, prevention of vertical HIV transmission with nevirapine was
ranked as number five compared to the other eight conditions. Treatment for childhood diseases and highly
active anti retroviral treatment (HAART) for HIV/AIDS were ranked higher. Group specific ranking followed
the same pattern, although the people living with HIV-group ranked HAART consistently as number one.
CONCLUSIONS: Stakeholders seem to rank prevention of vertical HIV transmission lower than treatment for
malaria, pneumonia and diarrhoea. Policies considering prevention of vertical transmission of HIV should
consider its implications. This study shows that stakeholders are open to considering evidence in assessing
the relative priority of different interventions competing for scarce resources. More research is needed to
Page 33 of 56
develop methods that can involve representative stakeholders, including the public, in good and legitimate
decisions on priorities.
Le Coeur, S., S. Kanshana, and G. Jourdain. 2003. "[HIV-1 transmission from mother to
child and its prevention]." Med Trop (Mars), 63(4-5):381-90.
Mother-to-child transmission of HIV-1 can occur during pregnancy, labor/delivery, or breastfeeding. Without
intervention HIV infection occurs in about 35% of infants born to HIV-infected women: 10% during
pregnancy, 15% during labor/delivery, and 10% during breastfeeding. As early as 1994, the PACTG 076ANRS 024 study documented the remarkable effectiveness of AZT in reducing mother-to-child HIV
transmission from 26% to 8% in women who did not breastfeed. Since then, AZT or multiple antiretroviral
therapies has been widely used in pregnant HIV-infected women in industrialized countries resulting in
decline of the transmission rate to less than 3%. In developing countries where most perinatal transmissions
occur, preventive treatment is more difficult to implement. Abbreviated treatment using AZT or nevirapine
(NVP) in a single dose to the mother during delivery and to the newborn reduces perinatal transmission but
to a lesser extent in comparison with standard treatment. Combination treatment using AZT + 3TC or AZT +
NVP is more effective. Elective cesarean section has also been proposed but is not recommended in
developing countries. To date the only alternative of proven efficacy for reducing transmission during
breastfeeding is formula feeding, but this method may be hazardous if sanitary conditions are poor. Studies
are currently under way to test the efficacy of antiretrovirals administered to the mother and/or infant in
reducing HIV transmission during breastfeeding.
Moodley, D., J. Moodley, H. Coovadia, G. Gray, J. McIntyre, J. Hofmyer, C. Nikodem,
D. Hall, M. Gigliotti, P. Robinson, L. Boshoff, and J. L. Sullivan. 2003. "A
multicenter randomized controlled trial of nevirapine versus a combination of
zidovudine and lamivudine to reduce intrapartum and early postpartum motherto-child transmission of human immunodeficiency virus type 1." J Infect Dis,
187(5):725-35.
To determine the efficacy and safety of 2 inexpensive and easily deliverable antiretroviral (ARV) regimens
for the prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) type 1
during labor and delivery, HIV-infected pregnant women were screened at 11 maternity health institutions in
South Africa and were enrolled in an open-label short course ARV regimen of either nevirapine (Nvp) or
multiple-dose zidovudine and lamivudine (Zdv/3TC). The overall estimated HIV-1 infection rates in 1307
infants by 8 weeks were 12.3% (95% confidence interval [CI], 9.7-15.0) for Nvp and 9.3% (95% CI, 7.0-11.6)
for Zdv/3TC (P=.11). Excluding infections detected within 72 h (intrauterine), new HIV-1 infections were
detected in 5.7% (95% CI, 3.7-7.8) and 3.6% (95% CI, 2.0-5.3) of infants in the Nvp and Zdv/3TC groups,
respectively, in the 8 weeks after birth. There were no drug-related maternal or pediatric serious adverse
events. Common complications were obstetrical for mothers (Nvp group, 24.3%; Zdv/3TC group, 26.3%)
and respiratory for infants (Nvp group, 16.1%; Zdv/3TC group, 17.0%). This study further confirms the
efficacy and safety of short-course ARV regimens in reducing MTCT rates in developing countries.
Morris, L., C. Pillay, C. Chezzi, P. Lupondwana, M. Ntsala, L. Levin, F. Venter, N.
Martinson, G. Gray, and J. McIntyre. 2003. "Low frequency of the V106M
mutation among HIV-1 subtype C-infected pregnant women exposed to
nevirapine." Aids, 17(11):1698-700.
Nevirapine used in single doses to prevent mother-to-child transmission has been shown to be associated
with the development of transient resistant mutations. Here we describe the presence of V106M in seven out
of 141 South African women (5%) 6 weeks after receiving nevirapine. V106M is a novel resistance mutation
found in subtype C viruses exposed to efavirenz. This mutation is thus also induced at a low frequency in
subtype C viruses exposed to single dose nevirapine.
Ngwena, C. 2003. "Access to health care services as a justiciable socio-economic right
under the South African constitution." Med Law Int, 6(1):13-23.
Page 34 of 56
This commentary describes and analyses the decision of the Constitutional Court of South Africa in Minister
of Health and Others v Treatment Action Campaign and Others where the South African government was
found to have violated the right of access to health care under the Constitution. Section 27(1) guarantees
everyone the right of access to health care services. Section 27(2) imposes on the state a duty to take
reasonable measures within its available resources to achieve the progressive realisation of this right. To the
extent that government was unreasonably delaying access to patently affordable life-saving therapy for the
prevention of mother-to-child transmission of HIV to a class of persons that was largely vulnerable and
indigent, it is submitted that the case was correctly decided. However, there is little doubt that the decision,
and in particular the prescriptive nature of the remedy granted by the Court and its budgetary implications,
do no sit easily with a traditional notion of separation of powers between the judiciary on the one hand, and
the executive and Parliament on the other. At the same time, it must be accepted that the remedy and its
budgetary implications are an inevitable consequence of the inclusion of justiciable socio-economic rights in
the Bill of Rights. The principles that were applied by the Court in determining the case were largely drawn
from jurisprudence developed by organs under treaty bodies, and in particular the Committee on Economic,
Social and Cultural Rights.
Ogundele, M. O. and J. B. Coulter. 2003. "HIV transmission through breastfeeding:
problems and prevention." Ann Trop Paediatr, 23(2):91-106.
The greatest burden of HIV infection in women and their children is disproportionately borne by the poorest
countries, especially in sub-Saharan Africa. Breastfeeding is a major health-promoting factor for infants and
children in developing countries but the risk of mother-to-child transmission (MTCT) of HIV by this route is
challenging traditional practices and health policies in low-resource countries. Maternal and infant factors
contributing to the risk of MTCT through breastfeeding are still poorly understood and not well researched.
Factors identified include: advanced clinical stages of infection in the mother; high maternal plasma HIV-1
load; presence of mastitis; and infant oral thrush. In many developing countries, international agencies are
providing support and recommendations for preventing MTCT of HIV-1 by breastfeeding. Preventive
strategies supported by WHO/UNICEF and charitable agencies in some sentinel centres in sub-Saharan
Africa include routine antenatal voluntary counselling and testing (VCT), PCR testing of infants of
seropositive mothers at 6 weeks of age, various combinations of a shortened period (3-6 mths) of exclusive
breastfeeding, perinatal administration of antiretrovirals (ARV) such as nevirapine and provision of
affordable and safe infant replacement feeds (presently given free by UNICEF in some centres). Many
problems, however, have hindered effective implementation of these interventions. In many poor
communities, even where VCT facilities are available, acceptance of HIV testing is low because there is fear
of stigmatisation by the spouse, family or community and compliance with complex drug regimens is
therefore poor. Other problems include the exorbitant cost of antiretroviral drugs, inadequately resourced
health care systems and unavailability or poor acceptance of safe breast-milk alternatives. The rate of mixed
feeding is high and so the risk of MTCT is increased. Continued promotion of exclusive breastfeeding for at
least 6 months, irrespective of HIV status, followed by a properly prepared, high energy, nutritious
complementary diet, with the possibility of early weaning to an animal milk formula, still appears to be the
most appropriate option for the poor in countries with high levels of MTCT not deriving any benefit from the
above strategies. While a longer period of breastfeeding would probably increase the risk of MTCT in
vulnerable communities, a shorter duration would certainly increase infant morbidity and mortality. Results of
investigations of the efficacy of ARV for protecting the infants of HIV-infected mothers during the
breastfeeding period are awaited.
Perez-Then, E., R. Pena, M. Tavarez-Rojas, C. Pena, S. Quinonez, M. Buttler, A.
Ammann, W. Hernandez, M. Goyanes, M. J. Miguez, and G. Shor-Posner. 2003.
"Preventing mother-to-child HIV transmission in a developing country: the
Dominican Republic experience." J Acquir Immune Defic Syndr, 34(5):506-11.
Transmission of HIV in the Dominican Republic occurs primarily through heterosexual contact. As part of a
continuing strategy to prevent and contain the spread of HIV infection, the Ministry of Health of the
Dominican Republic established an integrated package of interventions to reduce HIV mother-to-child
transmission that was initiated on May 15, 2000. The program was designed to be implemented in 3 phases.
The 1st phase included 4 mother and child hospitals; the 2nd phase included 8 mother and child health
institutions in Santo Domingo, the capital of the Dominican Republic, and 7 additional mother and child
Page 35 of 56
hospitals. The 3rd phase will include the remaining 12 mother and child health care institutions of the
Dominican Republic. Evaluation of the 1st year of this program, involving 8 hospitals and >40000 pregnant
women, identified specific benefits and limitations. Low numbers of voluntary counseling sessions
(6528/42666 = 28%) and inadequate number of HIV rapid tests (23067/42666 = 54%) were the 2 main
obstacles encountered. From the 23067 pregnant women tested, 581 (2.5%) were HIV positive.
Advantageous aspects included the successful administration of antiretroviral treatment to 89% (164/185) of
the mothers and 98% (183/186) of the children. Cesarean section was performed in 67% (124/185) of the
HIV-positive pregnant women, and infant formula was dispensed to 47% (87/186) of all cases. These
findings demonstrate the feasibility of implementing a large-scale program to prevent mother-to-child
transmission in a developing country.
Rely, K., S. M. Bertozzi, C. Avila-Figueroa, and M. T. Guijarro. 2003. "Costeffectiveness of strategies to reduce mother-to-child HIV transmission in Mexico,
a low-prevalence setting." Health Policy Plan, 18(3):290-8.
OBJECTIVE: To estimate and compare the cost-effectiveness of selected interventions to reduce mother-tochild transmission (MTCT) of HIV in Mexico. METHODS: A spreadsheet-based model was used to examine
five scenarios, each estimated using both zidovudine (ZDV) and nevirapine (NVP). Scenarios differ
according to coverage, type of voluntary counselling and testing (VCT), restriction to women at higher risk,
and whether rapid testing is offered at delivery. Averted adult infections due to VCT are also estimated, as
are savings due to averted treatment costs. Results are reported as cost per child infection prevented, net of
averted treatment costs (C/CIP). RESULTS: Among 958294 women attending public antenatal clinics,
increasing VCT coverage from 4% to 85% is estimated to prevent 102 paediatric and 8 adult infections at a
C/CIP of US dollars 42517 using ZDV. In the most restrictive scenario (III), 46 paediatric infections are
prevented with a C/CIP of US dollars 39220. Use of NVP increases C/CIP because the reduced drug cost is
more than offset by its reduced assumed effectiveness. The cost of detecting infected women
(approximately 90% of total) far exceeds treatment costs in such a low-prevalence setting. CONCLUSION:
Minimization of MTCT costs in low-prevalence settings should focus on VCT costs rather than drug costs.
Even the most cost-effective scenario modelled compares unfavourably with other, highly cost-effective
maternal/child interventions that still do not reach many Mexicans. However, it compares favourably against
several therapeutic maternal/child interventions available in the public sector's tertiary care hospitals.
Scotland, G. S., E. R. van Teijlingen, M. van der Pol, and W. C. Smith. 2003. "A review
of studies assessing the costs and consequences of interventions to reduce
mother-to-child HIV transmission in sub-Saharan Africa." Aids, 17(7):1045-52.
OBJECTIVE: To review the methods and findings of studies that assess the costs and consequences of
interventions to reduce mother-to-child HIV transmission in sub-Saharan Africa. DESIGN: Systematic
literature review. METHODS: A literature search was conducted to identify studies that assessed the costs
and consequences of interventions aimed at reducing mother-to-child HIV transmission in African
populations. The methodological quality of included studies was appraised using the British Medical Journal
Economic Evaluation Working Party checklist and data were extracted for comparison using a data
extraction template. RESULTS: Nine studies, all of which used modelling techniques to predict the costeffectiveness of anti-retroviral interventions, were identified for inclusion in the review. The quality of
reporting was found to be lacking in several key areas. In particular a lack of detail was given regarding
quantities of resources required for interventions, and the methods for valuing health outcomes and unit
costs. In general, the more recent evaluations report more favourable cost-effectiveness ratios than earlier
studies due to lower drug costs and in some cases the use of shorter drug regimens. CONCLUSIONS:
Comparisons between studies were hampered by variations in the values attached to model parameters and
by differences in the structure and design of models. The most encouraging findings have been reported for
the CDC short zidovudine regimen and the HIVNET012 single dose nevirapine regimen. The generalizability
of these findings is limited by the use of incremental costing, combined with uncertainty surrounding the
level of infrastructure required to implement the interventions. In low-income sub-Saharan countries, the
costs of strengthening the infrastructure to levels capable of providing such interventions, needs to be
assessed before an optimal policy for the prevention of mother-to-child HIV transmission in sub-Saharan
Africa can be established.
Page 36 of 56
Shetty, A. K., H. M. Coovadia, M. M. Mirochnick, Y. Maldonado, L. M. Mofenson, S. H.
Eshleman, T. Fleming, L. Emel, K. George, D. A. Katzenstein, J. Wells, C. C.
Maponga, A. Mwatha, S. A. Jones, S. S. Abdool Karim, and M. T. Bassett. 2003.
"Safety and trough concentrations of nevirapine prophylaxis given daily, twice
weekly, or weekly in breast-feeding infants from birth to 6 months." J Acquir
Immune Defic Syndr, 34(5):482-90.
Despite the success of antiretroviral prophylaxis in reducing mother-to-child HIV-1 transmission, postpartum
transmission through breast milk remains a problem. Antiretroviral administration to the infant during the
period of breast-feeding could protect against postnatal transmission. An open-label phase 1/2 study was
designed to assess the safety and trough concentrations of nevirapine (NVP) given once weekly (OW), twice
weekly (TW), or once daily (OD) to HIV-exposed breast-feeding infants for 24 weeks. Following maternal
dosing with 200 mg NVP orally at onset of labor, breast-feeding infants were randomized within 48 hours of
birth to 1 of 3 regimens: arm 1, NVP given OW (4 mg/kg from birth to 14 days, upward arrow to 8 mg/kg
from 15 days to 24 weeks), arm 2, NVP given TW (4 mg/kg from birth to 14 days, upward arrow to 8 mg/kg
from 15 days to 24 weeks), and arm 3, NVP given OD (2 mg/kg from birth to 14 days, upward arrow to 4
mg/kg from 15 days to 24 weeks). Trough NVP concentrations and clinical and laboratory abnormalities
were monitored. Of the 75 infants randomized (26 to OW, 25 to TW, and 24 to OD dosing), 63 completed
the 32-week follow-up visit. No severe skin, hepatic, or renal toxicity related to NVP was observed.
Neutropenia occurred in 8 infants. Trough NVP levels were lower than the therapeutic target (100 ng/mL) in
48 of 75 (64.0%) samples from infants in the OW arm, 3 of 65 (4.6%) samples in the TW arm, and 0 of 72
samples in the OD arm. Median (range) trough NVP concentrations were 64 ng/mL (range: <25-1519
ng/mL) with OW dosing; 459 (range: <25-1386 ng/mL) with TW dosing; and 1348 (range: 108-4843 ng/ml)
with OD dosing. Our data indicate that NVP prophylaxis for 6 months was safe and well tolerated in infants.
OD NVP dosing resulted in all infants with trough concentration greater than the therapeutic target and
maintenance of high drug concentrations. A phase 3 study is planned to assess the efficacy of OD infant
NVP regimen to prevent breast-feeding HIV-1 transmission.
Stringer, E. M., M. Sinkala, J. S. Stringer, E. Mzyece, I. Makuka, R. L. Goldenberg, P.
Kwape, M. Chilufya, and S. H. Vermund. 2003. "Prevention of mother-to-child
transmission of HIV in Africa: successes and challenges in scaling-up a
nevirapine-based program in Lusaka, Zambia." Aids, 17(9):1377-82.
BACKGROUND: Nearly half of perinatal HIV infection is preventable with nevirapine (NVP), which has
transformed the ability to confront this transmission route in resource-limited settings. METHODS: A NVPbased perinatal HIV prevention program initiated in Lusaka, Zambia in November 2001. RESULTS: The first
12 months cost US$221 000 and enabled 178 district health employees to be trained in voluntary counseling
and testing: 17 263 pregnant women were counseled for HIV, 12 438 (72%) were tested, and 2924 (24%)
were found to be infected with HIV. NVP has been taken by 1654 (57%) mothers and 1157 (40%) babies. It
is estimated that at least 190 infants have been spared HIV infection (11 per 1000 counseled women or 65
per 1000 identified HIV-infected women). CONCLUSIONS: Prevention of mother-to-child HIV transmission is
feasible and cost effective in resource-limited settings. In Lusaka, thousands of women have received
voluntary counseling and testing and NVP therapy under the present scheme. Patient attrition and nonadherence represented a major source of program inefficiency, which requires to be systematically
addressed.
Stringer, J. S., D. J. Rouse, M. Sinkala, E. A. Marseille, S. H. Vermund, E. M. Stringer,
and R. L. Goldenberg. 2003. "Nevirapine to prevent mother-to-child transmission
of HIV-1 among women of unknown serostatus." Lancet, 362(9398):1850-3.
Stringer, J. S., M. Sinkala, R. Goldenberg, S. Vermund, and E. Acosta. 2003.
"Monitoring nevirapine-based programmes for prevention of mother-to-child
transmission of HIV-1." Lancet, 362(9384):667.
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Sullivan, J. L. 2003. "Prevention of mother-to-child transmission of HIV--what next?" J
Acquir Immune Defic Syndr, 34 Suppl 1:S67-72.
Mother-to-child transmission (MTCT) of the human immunodeficiency virus (HIV) is a global problem. HIV
can be transmitted from mother-to-child at various stages of pregnancy including in utero, intrapartum and
during breastfeeding. A number of interventions have, therefore, been aimed at effectively providing
alternatives to breastfeeding and limiting the risk of newborn infection during delivery, by using caesarian
section as the mode of delivery and administering antiretroviral (ARV) drugs prepartum and peripartum.
However, these approaches are not always possible in developing countries and the use of ARV drugs, in
particular nevirapine, zidovudine and zidovudine/lamivudine, have been investigated in both developing
countries and developed countries. The studies have involved the administration of various ARV prophylaxis
regimens to HIV-infected pregnant women perinatally, either as monotherapy or in various combinations. In
some studies, infants have also received ARV prophylaxis. Although studies have enrolled different
populations and utilized various ARV drugs and regimens, encouraging reductions in the MTCT rates have
been reported. These interventions have raised concerns regarding the development of ARV-resistant HIV
strains. Mutations that confer resistance to nevirapine have been detected in pregnant women who received
this drug, but the emergence of these mutations was not associated with an increased risk of transmission of
HIV-1 to their infants. Studies are ongoing to determine if the presence of these mutations has implications
for the subsequent administration of nevirapine, either to prevent MTCT of HIV-1 or for the mother's own
health. Effective interventions that can reduce MTCT of HIV are now available worldwide. However, a
number of issues remain to be resolved, particularly methods to reduce the transmission of the virus during
breastfeeding and to deliver effective treatment for the mothers' own HIV infection.
Taha, T. E., N. I. Kumwenda, A. Gibbons, R. L. Broadhead, S. Fiscus, V. Lema, G.
Liomba, C. Nkhoma, P. G. Miotti, and D. R. Hoover. 2003. "Short postexposure
prophylaxis in newborn babies to reduce mother-to-child transmission of HIV-1:
NVAZ randomised clinical trial." Lancet, 362(9391):1171-7.
BACKGROUND: In sub-Saharan Africa, most women present late for delivery with unknown HIV status,
which limits the use of intrapartum nevirapine to prevent mother-to-child transmission of HIV. We aimed to
determine whether post-exposure prophylaxis of nevirapine plus zidovudine given to babies only reduced
transmission of HIV more than did a regimen of nevirapine alone. METHODS: We randomly assigned 1119
babies of Malawian women with HIV-1 who presented late (ie, within 2 h of expected delivery) to either
nevirapine alone or nevirapine and zidovudine. Both drugs were given immediately after birth: one dose of
nevirapine (2 mg/kg weight) was given as a single dose; babies in the nevirapine plus zidovudine group also
received zidovudine twice daily for 1 week (4 mg/kg weight). Infant HIV infection was determined at birth and
at 6-8 weeks. Primary outcome was HIV infection in babies at 6-8 weeks in those not infected at birth.
Analysis was by intention to treat. FINDINGS: The overall rate of mother-to-child transmission at 6-8 weeks
was 15.3% in 484 babies who received nevirapine and zidovudine and 20.9% in 468 babies who received
nevirapine only (p=0.03). At 6-8 weeks, in babies who were HIV negative at birth, 34 (7.7%) babies who had
nevirapine and zidovudine and 51 (12.1%) who received nevirapine only were infected (p=0.03)-a protective
efficacy of 36%. This finding remained after controlling for maternal viral load and other factors at baseline.
Adverse events were mild and of similar frequency in the two groups. INTERPRETATION: Postexposure
prophylaxis can offer protection against HIV infection to babies of women who missed opportunities to be
counselled and tested before or during pregnancy. The nevirapine and zidovudine regimen is safe and easy
to implement.
Temmerman, M., A. Quaghebeur, F. Mwanyumba, and K. Mandaliya. 2003. "Mother-tochild HIV transmission in resource poor settings: how to improve coverage?"
Aids, 17(8):1239-42.
OBJECTIVES: To review coverage of the current nevirapine prevention model in Coast Provincial General
Hospital (CPGH) in Mombasa, Kenya, and to reflect on alternative models to reduce mother-to-child
transmission (MTCT) of HIV. METHODS: At the antenatal clinic, health information is provided, followed by
pre-test HIV voluntary counselling and testing (VCT). Because many women deliver at home, HIV-infected
women are provided with a tablet of 200 mg nevirapine for themselves, and with 0.6 ml (6 mg) nevirapine in
Page 38 of 56
a luer lock syringe for the baby. Data on coverage are provided from antenatal records and delivery
registers. RESULTS: Out of 3564 first-visit pregnant women receiving health education, 2516 were
counselled (71%) and 2483 were tested (97%); 348 were HIV positive (14%), and 106 women took
nevirapine in labour, resulting in an overall coverage rate of 20%. In the same period, approximately 6000
women gave birth in CPGH, of whom 21% had attended a facility with VCT services. Assuming an overall
HIV prevalence of 14%, 840 mother-infant pairs could have received a preventative intervention with a
hospital policy of antepartum as well as intrapartum testing and treatment in place. CONCLUSION: The
coverage of perinatal MTCT was low as a result of a variety of programme elements requiring urgent
improvement at different levels. Alternative models, including intrapartum testing, should be considered as a
safety net for women without access to VCT before delivery, and recommendations for nevirapine should be
considered in the light of home deliveries.
Volmink, J. 2003. "HIV: mother to child transmission." Clin Evid, (9):785-94.
2002. "WHO and UNAIDS continue to support use of nevirapine for prevention of
mother-to-child HIV transmission." J Adv Nurs, 39(6):519.
Bhana, N., D. Ormrod, C. M. Perry, and D. P. Figgitt. 2002. "Zidovudine: a review of its
use in the management of vertically-acquired pediatric HIV infection." Paediatr
Drugs, 4(8):515-53.
Zidovudine is a thymidine analog that, after intracellular phosphorylation to zidovudine triphosphate
metabolite, inhibits HIV-specific reverse transcriptase and terminates proviral DNA. Zidovudine administered
to mildly symptomatic women with HIV infection in the antepartum (100mg orally 5 times/day), intrapartum (2
mg/kg intravenously over 1 hour then 1 mg/kg/h) and then to the neonate for 6 weeks (2 mg/kg), significantly
reduced the rate of vertical HIV transmission by about two thirds, in the absence of breast-feeding (The
Pediatric AIDS Clinical Trials Group 076 trial, standard protocol). Shorter zidovudine regimens, reduced the
risk of transmission of HIV by 50% in a non-breast-feeding population and by about 37% in breast-feeding
populations. Zidovudine (standard protocol) in combination with lamivudine was superior to zidovudine
alone. A short oral zidovudine regimen was not as effective as a two-dose oral nevirapine regime, although
the combination of short-course zidovudine plus lamivudine was as effective. Suppression of viral replication
in neonates, infants and children has been achieved with zidovudine when used in triple-therapy regimens
that include other antiviral drugs. Results from a trial of treatment-naive children indicate that the antiviral
efficacy of combinations of zidovudine and lamivudine or abacavir, given with the protease inhibitor
nelfinavir, is superior to treatment with this combination minus nelfinavir. When zidovudine was used in other
highly active antiretroviral therapy regimens significant improvements in surrogate markers were consistently
seen. Changing to ritonavir-containing regimens was superior to changing to treatment with two new
nucleoside reverse transcriptase inhibitors. Short- and long-term (up to 5.6 years) outcomes from clinical
trials showed that prenatal and neonatal exposure to zidovudine was generally well tolerated with the
exception of mild anemia that resolved spontaneously after treatment cessation. Zidovudine was generally
well tolerated as monotherapy in clinical trials of pediatric patients with HIV infection, and adverse events
were similar to those reported in adults, with anemia and neutropenia being the most common.
CONCLUSION: Zidovudine, as monotherapy or in combination with other antiretroviral agents, remains a
first-choice therapy for the prophylaxis of mother-to-child HIV transmission as shown by substantial
reductions in transmission rates. Where feasible, the optimal strategy to prevent vertical transmission is to
combine drug therapy with Cesarean section delivery and no breast-feeding. In addition, zidovudine in
combination with another nucleoside analogue and a protease inhibitor is a first- or second-choice therapy
for the treatment of pediatric HIV infection as significant and sustained reductions in viral load have been
shown in both plasma and cerebrospinal fluid.
Brocklehurst, P. 2002. "Interventions for reducing the risk of mother-to-child
transmission of HIV infection." Cochrane Database Syst Rev, (1):CD000102.
BACKGROUND: At the end of 1998 over 33 million people were infected with the human immunodeficiency
virus (HIV) and over one million children had been infected from their mothers. OBJECTIVES: The objective
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of this review was to assess what interventions may be effective in decreasing the risk of mother-to-child
transmission of HIV infection as well as their effect on neonatal and maternal mortality and morbidity.
SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register and the Cochrane
Controlled Trials Register were searched. SELECTION CRITERIA: Randomised trials comparing any
intervention aimed at decreasing the risk of mother-to-child transmission of HIV infection compared with
placebo or no treatment, or any two or more interventions aimed at decreasing the risk of mother-to-child
transmission of HIV infection. DATA COLLECTION AND ANALYSIS: Trial quality assessments and data
extraction were undertaken by the reviewer. MAIN RESULTS: Zidovudine Four trials comparing zidovudine
with placebo involving 1585 participants were included. Compared with placebo, there was a significant
reduction in the risk of mother-to-child transmission with any zidovudine (relative risk (RR) 0.54, 95%
confidence interval (CI) 0.42-0.69). There is no evidence that 'long course therapy' is superior to 'short
course therapy'. Nevirapine One trial compared intrapartum and postnatal nevirapine with intrapartum and
postnatal zidovudine in 626 women, the majority of whom breast fed their infants. Compared with
zidovudine, there was a significant reduction in the risk of mother-to-child transmission of HIV with
nevirapine (RR 0.58, 95% CI 0.40-0.83). No trials are available comparing nevirapine with placebo.
Caesarean section One trial comparing elective caesarean section with anticipation of vaginal delivery
involving 436 participants was included. Compared with vaginal delivery, there was a significant reduction in
the risk of mother-to-child transmission of HIV infection with caesarean section (RR 0.17, 95% CI 0.05-0.55).
Immunoglobulin One trial comparing hyperimmune immunoglobulin plus zidovudine with non-specific
immunoglobulin plus zidovudine involving 501 participants was included. The addition of hyperimmune
immunoglobulin to zidovudine does not appear to have any additional effect on the risk of mother-to-child
transmission (RR 0.67, 95% CI 0.29-1.55). REVIEWER'S CONCLUSIONS: Zidovudine, nevirapine and
delivery by elective caesarean section appear to be very effective in decreasing the risk of mother-to-child
transmission of HIV infection.
Brocklehurst, P. and J. Volmink. 2002. "Antiretrovirals for reducing the risk of mother-tochild transmission of HIV infection." Cochrane Database Syst Rev,
(1):CD003510.
BACKGROUND: At the end of 2000 it was estimated that over 36 million people were living with the human
immunodeficiency virus (HIV). This includes 1.4 million children less than 15 years of age. This is one of
several reviews assessing the available evidence for preventing mother-to-child transmission of HIV
infection. The other reviews will address other interventions, including Caesarean section, breast feeding,
vaginal lavage and vitamin A supplementation. OBJECTIVES: To assess which antiretroviral therapies may
be effective in decreasing the risk of mother-to-child transmission of HIV infection as well as their effect on
neonatal and maternal mortality and morbidity. SEARCH STRATEGY: We searched the Cochrane
Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. We also
searched conference abstracts from the International AIDS Conferences and Conference on Retroviruses
and Opportunistic Infections. SELECTION CRITERIA: Randomised trials comparing any antiretroviral
therapy aimed at decreasing the risk of mother-to-child transmission of HIV infection with placebo or no
treatment, or any two or more antiretroviral therapies or regimens aimed at decreasing the risk of mother-tochild transmission of HIV infection. DATA COLLECTION AND ANALYSIS: Two reviewers independently
extracted data and assessed trial quality. MAIN RESULTS: Zidovudine monotherapy Any zidovudine
regimen versus placebo significantly reduces the risk of mother-to-child transmission (Peto odds ratio (OR)
0.46, 95% confidence interval (CI) 0.35 to 0.60). Zidovudine also appears to decrease the risk of infant
death within the first year of birth (OR 0.57, 95% CI 0.38 to 0.85) and the risk of maternal death (OR 0.32,
95% CI 0.16 to 0.66). There is no evidence that zidovudine influences the incidence of premature delivery
(OR 0.86, 95% CI 0.57 to 1.29) or low birth weight (OR 0.74, 95% CI 0.53 to 1.04). The risk of transmission
using a 'short-short' course of zidovudine (from 35 weeks in pregnancy for the mother and for the baby until
3 days old) was higher than the risk using a 'long-long' course (from 28 weeks in pregnancy for the mother
and for the baby until 6 weeks old), (OR 2.55, 95% CI 1.26 to 5.18). However, the effectiveness of the 'longshort' course (from 28 weeks in pregnancy for the mother and for the baby until 3 days old) and the 'shortlong' course (from 35 weeks in pregnancy for the mother and for the baby until 6 weeks old) did not differ
from that of the 'long-long' course. Nevirapine One large randomised controlled trial demonstrates that
nevirapine given to mothers as a single dose at the onset of labour and to babies as a single dose within 72
hours of birth is more effective than an intrapartum and post-partum regimen of zidovudine (OR 0.51, 95%
CI 0.33 to 0.79). When nevirapine is given to mothers already receiving standard antiretroviral therapy,
however, there appears to be no additional advantage (OR 1.10, 95% CI 0.42 to 2.86). Combination
Therapy Preliminary findings of the effect of combination therapy using zidovudine and lamivudine (3TC)
suggest a decrease in the risk of transmission when the combination is given during the antenatal and
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intrapartum period or during the intrapartum and postpartum period compared with placebo. There is no
evidence that intrapartum zidovudine and lamivudine alone are sufficient to decrease the risk of
transmission compared with placebo. REVIEWER'S CONCLUSIONS: Implications for practice The
randomised trials included in this review provide evidence that short course zidovudine and single-dose
nevirapine are effective therapies for reducing mother-to-child transmission of HIV. The challenge for low
and middle income countries will be to institute this therapy in practice. In industrialised countries practice
has already moved on from the current evidence and combination antiretroviral therapy aimed primarily at
preventing disease progression in the mother is the standard of care. Implications for research The potential
value of nevirapine used for longer durations in breastfeeding populations should be considered as it may
further reduce the risk of mother-to-child transmission, particularly if combined with early weaning. On-going
evaluation of combination antiretroviral therapy is essential and will have an immediate benefit for countries
with the resources to adopt such treatment. The search for effective, affordable, safe and acceptable
alternatives to antiretroviral therapy for reducing mother-to-child transmission in resource poor countries
should remain on the research agenda.
—. 2002. "Antiretrovirals for reducing the risk of mother-to-child transmission of HIV
infection." Cochrane Database Syst Rev, (2):CD003510.
BACKGROUND: At the end of 2000 it was estimated that over 36 million people were living with the human
immunodeficiency virus (HIV). This includes 1.4 million children less than 15 years of age. This is one of
several reviews assessing the available evidence for preventing mother-to-child transmission of HIV
infection. The other reviews will address other interventions, including Caesarean section, breast feeding,
vaginal lavage and vitamin A supplementation. OBJECTIVES: To assess which antiretroviral therapies may
be effective in decreasing the risk of mother-to-child transmission of HIV infection as well as their effect on
neonatal and maternal mortality and morbidity. SEARCH STRATEGY: We searched the Cochrane
Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. We also
searched conference abstracts from the International AIDS Conferences and Conference on Retroviruses
and Opportunistic Infections. SELECTION CRITERIA: Randomised trials comparing any antiretroviral
therapy aimed at decreasing the risk of mother-to-child transmission of HIV infection with placebo or no
treatment, or any two or more antiretroviral therapies or regimens aimed at decreasing the risk of mother-tochild transmission of HIV infection. DATA COLLECTION AND ANALYSIS: Two reviewers independently
extracted data and assessed trial quality. MAIN RESULTS: Zidovudine monotherapy Based on four trials
any zidovudine regimen versus placebo significantly reduces the risk of mother-to-child transmission (Peto
odds ratio (OR) 0.46, 95% confidence interval (CI) 0.35 to 0.60). Zidovudine also appears to decrease the
risk of infant death within the first year of birth (OR 0.57, 95% CI 0.38 to 0.85) and the risk of maternal death
(OR 0.32, 95% CI 0.16 to 0.66). There is no evidence that zidovudine influences the incidence of premature
delivery (OR 0.86, 95% CI 0.57 to 1.29) or low birth weight (OR 0.74, 95% CI 0.53 to 1.04). The risk of
transmission using a 'short-short' course of zidovudine (from 35 weeks in pregnancy for the mother and for
the baby until 3 days old) was higher than the risk using a 'long-long' course (from 28 weeks in pregnancy
for the mother and for the baby until 6 weeks old), (OR 2.33, 95% CI 1.16 to 4.68). However, the
effectiveness of the 'long-short' course (from 28 weeks in pregnancy for the mother and for the baby until 3
days old) and the 'short-long' course (from 35 weeks in pregnancy for the mother and for the baby until 6
weeks old) did not differ from that of the 'long-long' course. Nevirapine One large randomised controlled trial
demonstrates that nevirapine given to mothers as a single dose at the onset of labour and to babies as a
single dose within 72 hours of birth is more effective than an intrapartum and post-partum regimen of
zidovudine (OR 0.51, 95% CI 0.33 to 0.79). When nevirapine is given to mothers already receiving standard
antiretroviral therapy, however, there appears to be no additional advantage (OR 1.10, 95% CI 0.42 to 2.86).
Combination Therapy Preliminary findings of the effect of combination therapy using zidovudine and
lamivudine (3TC) suggest a decrease in the risk of transmission when the combination is given during the
antenatal and intrapartum period or during the intrapartum and postpartum period compared with placebo.
There is no evidence that intrapartum zidovudine and lamivudine alone are sufficient to decrease the risk of
transmission compared with placebo. REVIEWER'S CONCLUSIONS: Implications for practice The
randomised trials included in this review provide evidence that short course zidovudine and single-dose
nevirapine are effective therapies for reducing mother-to-child transmission of HIV. The challenge for low
and middle income countries will be to institute this therapy in practice. In industrialised countries practice
has already moved on from the current evidence and combination antiretroviral therapy aimed primarily at
preventing disease progression in the mother is the standard of care. Implications for research The potential
value of nevirapine used for longer durations in breastfeeding populations should be considered as it may
further reduce the risk of mother-to-child transmission, particularly if combined with early weaning. On-going
evaluation of combination antiretroviral therapy is essential and will have an immediate benefit for countries
with the resources to adopt such treatment. The search for effective, affordable, safe and acceptable
Page 41 of 56
alternatives to antiretroviral therapy for reducing mother-to-child transmission in resource poor countries
should remain on the research agenda.
Creese, A., K. Floyd, A. Alban, and L. Guinness. 2002. "Cost-effectiveness of HIV/AIDS
interventions in Africa: a systematic review of the evidence." Lancet,
359(9318):1635-43.
BACKGROUND: Evidence for cost-effectiveness of interventions for HIV/AIDS in Africa is fragmentary.
Cost-effectiveness is, however, highly relevant. African governments face difficult choices in striking the right
balance between prevention, treatment, and care, all of which are necessary to deal comprehensively with
the epidemic. Reductions in drug prices have raised the priority of treatment, though treatment access is
restricted. We assessed the existing cost-effectiveness data and its implications for value-for-money
strategies to combat HIV/AIDS in Africa. METHODS: We undertook a systematic review using databases
and consultations with experts. We identified over 60 reports that measured both the cost and effectiveness
of HIV/AIDS interventions in Africa. 24 studies met our inclusion criteria and were used to calculate
standardised estimates of the cost (US$ for year 2000) per HIV infection prevented and per disabilityadjusted life-year (DALY) gained for 31 interventions. FINDINGS: Cost-effectiveness varied greatly between
interventions. A case of HIV/AIDS can be prevented for $11, and a DALY gained for $1, by selective blood
safety measures, and by targeted condom distribution with treatment of sexually transmitted diseases.
Single-dose nevirapine and short-course zidovudine for prevention of mother-to-child transmission, voluntary
counselling and testing, and tuberculosis treatment, cost under $75 per DALY gained. Other interventions,
such as formula feeding for infants, home care programmes, and antiretroviral therapy for adults, cost
several thousand dollars per infection prevented, or several hundreds of dollars per DALY gained.
INTERPRETATION: A strong economic case exists for prioritisation of preventive interventions and
tuberculosis treatment. Where potentially exclusive alternatives exist, cost-effectiveness analysis points to
an intervention that offers the best value for money. Cost-effectiveness analysis is an essential component
of informed debate about priority setting for HIV/AIDS.
Eshleman, S. H., L. A. Guay, T. Fleming, A. Mwatha, M. Mracna, G. Becker-Pergola, P.
Musoke, F. Mmiro, and J. B. Jackson. 2002. "Survival of Ugandan infants with
subtype A and D HIV-1 infection (HIVNET 012)." J Acquir Immune Defic Syndr,
31(3):327-30.
Virologic factors may influence survival of HIV-1-infected infants. We compared survival of Ugandan infants
with subtype A and subtype D HIV-1 infection. This study was performed in the context of the Ugandan
clinical trial HIVNET 012, which compared the efficacy of single-dose nevirapine (NVP) and short-course
zidovudine (AZT) for prevention of HIV-1 mother-to-child transmission. HIV-1 subtypes were determined by
phylogenetic analysis of HIV-1 protease and reverse transcriptase sequences from 32 women in the NVP
arm and 54 women in the AZT arm of HIVNET 012 whose infants were HIV-1 infected by 6 to 8 weeks of
age. We found no association between HIV-1 subtype (A vs. D) and infant survival in this cohort. Further
studies are needed to evaluate whether HIV-1 subtype influences clinical outcome in pediatric HIV-1
infection.
Eshleman, S. H. and J. B. Jackson. 2002. "Nevirapine resistance after single dose
prophylaxis." AIDS Rev, 4(2):59-63.
Nevirapine (NVP) is a potent non-nucleoside inhibitor of HIV-1 reverse transcriptase. In 1999, the HIVNET
012 trial in Uganda demonstrated that a simple regimen of NVP prophylaxis can dramatically reduce the rate
of HIV-1 mother-to-child transmission (MTCT). In the HIVNET 012 regimen, women received a single dose
of NVP in labor, and infants received a single dose of NVP within 72 h of birth. The simplicity, efficacy, and
low cost of the HIVNET 012 regimen are attractive for prevention of MTCT in resource-poor settings. Plans
are underway to implement this regimen in several resource-poor countries. Single mutations in HIV-1 RT
can cause high level NVP-resistance and are likely to exist in most HIV-1 infected patients at low levels prior
to antiretroviral drug exposure. This favors emergence of NVP-resistant HIV-1 following NVP exposure.
NVP-resistant HIV-1 has been shown to emerge in some women and infants following single dose NVP.
Emergence of NVP-resistant HIV-1 in this setting is more common among women with high baseline viral
loads and low baseline CD4 cell counts. The rate of NVP-resistance in women receiving single dose NVP
Page 42 of 56
prophylaxis may also be influenced by HIV-1 subtype. The NVP-resistant HIV-1 typically fades from
detection in women and infants over time. We review studies examining the emergence and fading of NVPresistant HIV-1 in women and infants who received single dose NVP prophylaxis, and discuss the potential
clinical relevance of NVP-resistance in this setting.
Gerntholtz, L. 2002. "South Africa: highest court orders government to provide
antiretrovirals to prevent mother-to-child transmission." Can HIV AIDS Policy Law
Rev, 7(2-3):50-2.
On 5 July 2002, South African treatment activists won a significant victory when the Constitutional Court
ordered the South African government to make the antiretroviral drug nevirapine available in public hospitals
and clinics for the purposes of preventing mother-to-child transmission of HIV. The Court also ruled the
government has a constitutional obligation to implement a program to realize the right of pregnant women
and their newborn children to access health services to prevent transmission.
—. 2002. "Preventing mother-to-child transmission: landmark decision by South African
court." Can HIV AIDS Policy Law Rev, 6(3):1, 20-4.
On 14 December 2001, the High Court of South Africa delivered its judgment in Treatment Action Campaign
et al v Minister of Health et al, ruling that the government was in breach of its constitutional obligations and
must promptly develop and implement a comprehensive national program to prevent mother-to-child
transmission of HIV, including making antiretroviral drugs available for this purpose. This article summarizes
the legal arguments and the outcome of a case that is of global significance in holding governments
accountable for their obligations to progressively realize the human right to health.
Hashimoto, H., S. H. Kapiga, and Y. Murata. 2002. "Mass treatment with nevirapine to
prevent mother-to-child transmission of HIV/AIDS in sub-Saharan African
countries." J Obstet Gynaecol Res, 28(6):313-9.
OBJECTIVE: In 2001, an estimated 800000 children were newly infected with HIV, almost all through
mother-to-child transmission (MCTC), and 90% of these children were born in Africa. In such resource-poor
settings, cheaper and more easily administered antiretroviral drugs should be available for use. Mass
treatment of an intrapartum and neonatal single dose of nevirapine regimen has been suggested as an
effective strategy to prevent MCTC, yet this strategy has never been conducted in clinical trials. By
discussing the advantages and disadvantages of it, we analyze the possibility of implementing this regimen.
METHODS: We reviewed public health strategies to prevent MCTC in resource-poor settings, and discuss
whether or not mass treatment of an intrapartum and neonatal single dose of nevirapine regimen can be
recommended as one therapy in sub-Saharan Africa due to its simplicity of distribution and use, long-term
efficacy, and cost-effectiveness. RESULT: Recent studies in Uganda showed the high efficacy and costeffectiveness of a single dose of nevirapine only to HIV/AIDS-positive pregnant women. The characteristics
of nevirapine also meet the requirements of mass treatment. Mass treatment of nevirapine would increase
access to antiretroviral drugs among pregnant women because they can access nevirapine without
volunteer counseling and testing, which 31% of pregnant women in developing countries refused to accept
due to the fear of stigmatization. No serious adverse effects or drug resistance to this regimen were reported
through the studies in Uganda. CONCLUSION: Mass treatment of a single-dose nevirapine can be
recommended as one alternative therapy, and further research is recommended to obtain more information
about the efficacy, side-effects, drug resistance, and compliance of this strategy.
Hudson, C. P., J. Moodley, and A. N. Smith. 2002. "Stage of the epidemic and viral
phenotype should influence recommendations regarding mother-to-child
transmission of HIV-1." Lancet Infect Dis, 2(2):115-9.
This article argues for a new approach to use of nevirapine in the prevention of vertical transmission of HIV1. Existing antenatal surveillance should be strengthened to plan geographical allocation, and subsequent
evaluation, of a "nevirapine plus" programme. As the epidemic evolves the programme should also and,
ideally, care should be tailored to individual women. Underpinning this approach is evidence that a more
Page 43 of 56
virulent viral phenotype appears in many patients with advanced HIV-1 infection. This phenotype will
become more common at the population level as the epidemic progresses. As efficacy of zidovudine
correlates with viral phenotype, and use of the drug may alter phenotype, there is an urgent need for a
replacement that is safe to use with nevirapine.
Kahn, J. G. and E. Marseille. 2002. "A saga in international HIV policy modeling:
preventing mother-to-child HIV transmission." J Policy Anal Manage, 21(3):499505.
Kingston, M. and E. Carlin. 2002. "Treatment of sexually transmitted infections with
single-dose therapy: a double-edged sword." Drugs, 62(6):871-8.
Since the advent of the antimicrobial era, single-dose therapy has been a valuable tool in the management
of genital infection. Most of the common sexually transmitted infections (STIs) such as gonorrhoea, syphilis,
trichomoniasis and chancroid can be treated in this way, as can genital infections which are not sexually
transmitted such as bacterial vaginosis and genital tract candidiasis. Until recently, treatment for Chlamydia
trachomatis infection required a multi-dose regimen, but single-dose azithromycin has now been shown to
be an effective and acceptable alternative to this. Unfortunately, eradicative therapy has proven to be
elusive for the viral STIs such as genital herpes simplex infection, human papilloma virus infection and
human immunodeficiency virus (HIV) infection. The main advantage of single-dose therapy lies in its
convenience and in its ability to ensure virtually 100% compliance. This addresses the problems of reduced
clinical efficacy and the difficulties in assessing the response to therapy which complicates poor treatment
compliance. However, some single-dose regimens for STIs do have drawbacks, particularly in certain
situations. This may be with respect to efficacy, for example in syphilis with single-dose benzathine penicillin
therapy, particularly for pregnant women and individuals infected with HI. Alternatively, it may involve
toxicity, for example with single-dose metronidazole therapy for trichomoniasis or bacterial vaginosis where
a higher rate of gastrointestinal adverse effects may be expected than if a lower multi-dose regimen is used.
In addition, single-dose therapy, for example with nevirapine, given to the mother in labour and to the baby
after delivery significantly reduces the risk of mother to child HIV transmission, but resistance mutations are
frequently detected in the viral genome after the brief exposure to the drug, which could jeopardise its future
use. Single-dose therapy clearly has both advantages and disadvantages. We have reviewed a range of
these in a variety of situations, focussing on their applications, effectiveness, compliance and toxicity,
highlighting how single-dose therapy may be a double-edged sword.
Pillay, C., H. Bredell, J. McIntyre, G. Gray, and L. Morris. 2002. "HIV-1 subtype C
reverse transcriptase sequences from drug-naive pregnant women in South
Africa." AIDS Res Hum Retroviruses, 18(8):605-10.
The HIV-1 reverse transcriptase genes from 37 HIV-1-positive pregnant women attending an antenatal
clinical in Soweto, South Africa were sequenced and analyzed for the presence of drug resistance
mutations. All women were antiretroviral drug naive, but were being screened as potential participants in
clinical trials of antiretroviral drugs aimed at preventing mother-to-child transmission. Sequence analysis
revealed that all belonged to HIV-1 subtype C, the predominant subtype among heterosexual populations in
South Africa. Twenty-three amino acid loci associated with resistance to zidovudine, lamivudine, didanosine,
stavudine, and nevirapine were examined and found not to encode mutations that would confer resistance to
these drugs. Polymorphisms at these loci occurred infrequently, with three patients harboring the A98S and
V179I polymorphisms. An additional three patients harbored V118I, which can function as an accessory
resistance mutation, but in this context is also likely to be a polymorphism. These data show that pregnant
women who are candidates for receiving antiretroviral drug therapies do not contain naturally occurring or
preexisting drug resistance mutations and that such drug therapies are likely to be highly effective in this
setting.
Skordis, J. and N. Nattrass. 2002. "Paying to waste lives: the affordability of reducing
mother-to-child transmission of HIV in South Africa." J Health Econ, 21(3):40521.
Page 44 of 56
It is estimated that each HIV-positive child in South Africa costs the government more in terms of health and
welfare expenses than it does to reduce mother-to-child transmission (MTCT) of HIV through the use of
antiretroviral regimens (where the mother continues to breast-feed). Programmes to reduce MTCT of
HIV/AIDS are, thus, clearly affordable. Using Nevirapine (according to the HIVNET 012 Protocol) saves
more lives and [corrected] is more cost-effective than using Zidovudine (CDC 2 weeks regime).
Volmink, J. 2002. "Mother to child transmission of HIV." Clin Evid, (7):709-16.
—. 2002. "Mother to child transmission of HIV." Clin Evid, (8):780-7.
Woods, D. 2002. "An interim plan to reduce mother-to-child HIV infection in South
Africa." S Afr Med J, 92(6):394.
2001. "Rwanda to receive cheaper anti-HIV drugs for chronic treatment and free
viramune to prevent viral transmission from mother to child." Sadj, 56(4):210.
2001. "Giving away HIV drugs is not as easy as it seems." AIDS Alert, 16(11):143-4,
137.
When officials with Boehringer ingelheim announced in July 2000 that the company would make its HIV
antiretroviral drug nevirapine (Viramune) available to any pregnant women in sub-Saharan Africa who need
it for the prevention of mother-to-child transmission of HIV, they thought their biggest problem would be to
meet the flood of demand. They were wrong. Why has demand been so low?
2001. "Nevirapine warning on post-exposure prophylaxis." AIDS Treat News, (358):6-8.
Nevirapine should not be used to prevent infection after HIV exposure, except in unusual circumstances,
due to the risk of side effects. This warning does not affect its use in HIV treatment, or in prevention of
mother to child transmission.
Dovie Akue, J. P., P. Babaki, F. Barre-Sinoussi, N. Charpak, G. de The, M. Ferreira
Rea, C. Huraux, B. Ndiaye, H. Pratomo, N. M. Samuel, C. Wilfert, and R.
Zetterstrom. 2001. "Further views by the Erice working group on mother-to-child
transmission of HIV type 1." Acta Paediatr, 90(1):102-3.
Eshleman, S. H., G. Becker-Pergola, M. Deseyve, L. A. Guay, M. Mracna, T. Fleming,
S. Cunningham, P. Musoke, F. Mmiro, and J. B. Jackson. 2001. "Impact of
human immunodeficiency virus type 1 (hiv-1) subtype on women receiving
single-dose nevirapine prophylaxis to prevent hiv-1 vertical transmission (hiv
network for prevention trials 012 study)." J Infect Dis, 184(7):914-7.
In Uganda, the HIV Network for Prevention Trials (HIVNET) 012 study recently demonstrated that singledose nevirapine (Nvp) prophylaxis is effective for preventing mother-to-child transmission (MTCT) of human
immunodeficiency virus type 1 (HIV-1). This exploratory study examines the relationship between HIV-1
subtype, MTCT, and the development of Nvp resistance (Nvp(R)) in women enrolled in HIVNET 012. For
102 women (32 whose infants were HIV-1 infected by age 6-8 weeks and 70 whose infants were
Page 45 of 56
uninfected), HIV-1 subtypes included 50 (49%) subtype A, 35 (34%) subtype D, 4 (4%) subtype C, 12 (12%)
recombinant subtype, and 1 unclassified. There was no apparent difference in the rate of MTCT among
women with subtype A versus D (adjusted odds ratio [OR], 1.24; 95% confidence interval [CI], 0.45-3.43).
Nvp(R) mutations were detected more frequently at 6-8 weeks postpartum in women with subtype D than in
women with subtype A (adjusted OR, 4.94; 95% CI, 1.21-20.22). Additional studies are needed to further
define the relationship between HIV-1 subtype and Nvp(R) among women receiving Nvp prophylaxis.
Hayashi, T. 2001. "[U.S. warns on some use of anti-AIDS drug]." Yakugaku Zasshi,
121(9):679-82.
The new way with nevirapine was reported to prevent mother-to-child transmission of the AIDS virus (HIV)
that also is less costly and markedly more effective than the standard therapy with AZT in the third world.
The more practical therapy comes from substituting one marketed drug, nevirapine, for the standard drug,
AZT. It was proposed that widescale use of nevirapine in developing countries could potentially prevent
300,000 to 400,000 newborns each year from beginning life infected with HIV. But in September, 2000, the
Center for Disease Control and Prevention (CDC) received reports of life-threatening hepatotoxicity (liver
damage) among health care workers taking nevirapine for post-exposure prophylaxis (PEP) after
occupational exposure to HIV. Furthermore, persons taking nevirapine regimens for PEP after HIV exposure
also are at risk for serious and adverse events. The federal Food and Drug Administration (FDA) had
identified 22 cases of severe liver, skin and muscle damage related to nevirapine taken after possible
exposure to HIV from March 1997 through September 2000. Nevirapin has not been recommended for PEP
use, and has previously been associated with instances of serious skin or muscle conditions, liver damage,
and death when used for treating HIV-infected individuals. In most circumstances, the risks associated with
nevirapine as part of an occupational PEP regimen might outweigh the anticipated benefits.
Maddocks, S. and D. Dwyer. 2001. "The role of non-nucleoside reverse transcriptase
inhibitors in children with HIV-1 infection." Paediatr Drugs, 3(9):681-702.
Over 1.4 million of the worlds' children are infected with HIV-1, mostly acquired in the perinatal period.
Antiviral therapeutic options for children with HIV-1 infection have lagged behind those for infected adults.
However, we now know that prevention of perinatal HIV-1 transmission to children is possible and that
combination therapy for the management of infected children is efficacious. Non-nucleoside reverse
transcriptase inhibitors (NNRTIs) are developing a more prominent role in combination therapy regimens,
particularly as alternatives to protease inhibitors. They also have a role in preventing perinatal transmission,
where it has been shown that only 2 doses of the NNRTI nevirapine can significantly reduce mother-to-child
transmission of HIV-1. This has major therapeutic implications, particularly in areas where combination
therapy is not readily available. Palatable paediatric formulations of NNRTIs are available or are being
developed. Whilst pharmacokinetic data regarding the use of antiretrovirals in children remain scarce,
published clinical trials have demonstrated the efficacy of NNRTIs when used as part of combination
regimens in the management of HIV-1 infected children. The toxicity profile of NNRTIs is relatively
favourable; however, severe skin rash, hepatotoxicity and central nervous system adverse effects with
various NNRTIs can lead to treatment cessation. The development of class resistance with single step
mutations in the reverse transcriptase gene remains a major therapeutic problem with this class of
antiretrovirals. Novel NNRTIs under development are of interest either because of improved
pharmacodynamics, reduced toxicity profiles or because of action against NNRTI-mutation containing
resistant virus. There are no data available yet on the use of these drugs in the paediatric population.
Morris, L., C. Pillay, G. Gray, and J. McIntyre. 2001. "HIV-1 drug resistance and motherto-child transmission." Sadj, 56(12):614-6.
The use of antiretroviral drug therapies in HIV-1 infected pregnant women and their infants has resulted in
significant reductions in the rates of mother-to-child transmission of HIV-1. A number of drugs that target the
reverse transcriptase enzyme have been tested either alone or in combination in short-course regimens
tailored for use in developing countries. The drug of choice is nevirapine, which is cheap, easy to administer
and highly effective even following a single dose to mother and child. However, this regimen is associated
with the selection of mutations associated with drug resistance. While these mutations do not compromise
the ability of nevirapine to prevent mother-to-child transmission there is some concern that they may
compromise future treatment options. Here we review the current data on HIV-1 drug resistance mutations
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and what they might mean in terms of efficacy of antiretroviral therapies to prevent mother-to-child
transmission.
Newell, M. L. 2001. "Prevention of mother-to-child transmission of HIV: challenges for
the current decade." Bull World Health Organ, 79(12):1138-44.
In June 2001 the United Nations Special Assembly on HIV/AIDS set reduction targets of 20% and 50% for
the numbers of children newly infected with HIV by 2005 and 2010 respectively. Are these targets
achievable? Antiretroviral monotherapy during pregnancy, delivery, and the neonatal period can reduce the
rate of mother-to-child transmission of HIV-1 by two-thirds in non-breastfeeding populations. Shorter and
simpler regimens of monotherapy have been associated with a reduction of 50% in such transmission
among non-breastfeeding populations and of up to 40% in breastfeeding populations. Delivery by elective
caesarean section is associated with a halving of the risk of mother-to-child transmission. However,
breastfeeding poses a substantial additional risk of acquisition of HIV, and if prolonged it more than doubles
the overall rate of transmission. Rates below 2% are being reported from settings where combination
therapy is applied during pregnancy and delivery, delivery is by elective caesarean section, and
breastfeeding does not take place. In breastfeeding populations where elective caesarean delivery is not an
option but peripartum antiretroviral therapy is used, rates at six weeks are about 10% but can be 25% or
more after 18 months of breastfeeding. More widely applicable interventions are being developed, such as
cleansing of the birth canal and antiretroviral therapy during the breastfeeding period.
Podzamczer, D. and E. Fumero. 2001. "The role of nevirapine in the treatment of HIV-1
disease." Expert Opin Pharmacother, 2(12):2065-78.
Nevirapine (Viramune, Boehringer Ingelheim) is a non-nucleoside reverse transcriptase (RT) inhibitor
(NNRTI) effective in the treatment of HIV-1 infected antiretroviral-naive and -experienced patients. Some
recent studies have suggested that nevirapine-based regimens may have an efficacy similar to protease
inhibitor (PI)-based regimens, at least in naive patients with CD4+ > 200 microl, while it lacks the drawbacks
inherent in PI-containing regimens, such as lipodystrophy and metabolic alterations. Switching from a PIcontaining regimen to a nevirapine-containing regimen seems to retain the virological response to therapy
and it may also limit or reverse the development of some metabolic disorders induced by PIs. Nevirapine is
also effective in preventing mother-to-child transmission of HIV-1 disease and in the treatment of HIV-1
infected children. Nevirapine is well-tolerated, rash being the most common severe adverse effect observed.
Hepatotoxicity may also appear with nevirapine, mainly in patients with chronic hepatitis C and/or altered
liver function tests. This side effect may occasionally be life-threatening but it can be safely managed in
most patients.
Walley, J., S. Witter, and A. Nicoll. 2001. "Simplified antiviral prophylaxis with or and
without artificial feeding to reduce mother-to-child transmission of HIV in low and
middle income countries: modelling positive and negative impact on child
survival." Med Sci Monit, 7(5):1043-51.
BACKGROUND: Antiviral prophylaxis is recommended for HIV positive mothers to prevent mother-to-child
transmission of HIV. To date UNAIDS and WHO policy has been based on a study in Thailand which
showed a reduction in transmission by half with short course AZT (Zidovudine) treatment together with
artificial feeding. We modelled the possible positive and negative effects on child deaths in low and middle
resource developing country settings of two interventions to reduce mother to child transmission (MTCT) of
HIV: antenatal testing, short-course antivirals (zidovudine or nevirapine), firstly with and then without artificial
feeding. MATERIAL AND METHODS: Estimates are made of child lives likely to be saved by the
programme by age ten years, balanced against increases in deaths due to more uninfected mothers
choosing to use artificial feeds where these are part of the intervention. Mid-point values for variables
affecting the balance of mortality gains and losses are taken from recent published data for low and middle
income developing countries and a sensitivity analysis is undertaken. RESULTS: In low income settings the
use of antivirals alone would result in an estimated gain in child survival of around 0.36%, representing 360
deaths avoided from a birth cohort of 100,000 by age 10 years. Adding artificial feeding could reduce the
gain to 0.03% (30 deaths avoided). In middle income settings the gain from antivirals alone would be 0.26%
but as 'spill-over' of artificial feeding to uninfected women was more likely it could result in a net increase of
Page 47 of 56
child deaths of up to 1.08% (1,080 additional deaths). A sensitivity analysis emphasised this potential for
regimens using artificial feeding if progamme participation was low, and under most circumstances in middle
income settings. CONCLUSIONS: HIV testing and use of antivirals by infected mothers, if well implemented,
will be effective at a population level in reducing MTCT. However the addition of artificial feeding is
potentially be a high risk strategy, especially in middle income countries.
2000. "Prevention of mother-child HIV transmission: progress and problems." Prescrire
Int, 9(47):92-5.
(1) Since 1994, zidovudine administration to pregnant women and their newborns has been the reference
prophylaxis for mother-child HIV transmission. (2) Three trials done in Thailand and Africa show that
zidovudine therapy during the last few weeks of pregnancy reduces the risk of transmission, especially when
breast-feeding is avoided. (3) A retrospective study done in the United States suggests that even very late
zidovudine administration may benefit the mother and/or her child. (4) A trial done in Uganda suggests that a
single dose of nevirapine has better preventive activity than a very short course of zidovudine in women who
breastfeed. (5) There are very few data on the risk-benefit ratio of multidrug antiretroviral regimens in
pregnant women. (6) Eight cases of mitochondrial involvement have been diagnosed in France in children
exposed to zidovudine or to the zidovudine + lamivudine combination. These cases call for long-term close
monitoring of children exposed to antiretroviral drugs in utero. To limit the duration of fetal exposure, the
third trimester of pregnancy is now recommended as the safest time to start antiretroviral prophylaxis. (7)
Despite a randomised trial and a meta-analysis suggesting that elective caesarean section prevents motherchild HIV transmission, the value of such surgery remains controversial.
2000. "Inexpensive AIDS drug still reduces HIV transmission from mother to child after 1
year." AIDS Read, 10(9):522.
Ades, A. E., J. Ratcliffe, D. M. Gibb, and M. J. Sculpher. 2000. "Economic issues in the
prevention of vertical transmission of HIV." Pharmacoeconomics, 18(1):9-22.
In the absence of interventions, 20% of infants born to women infected with HIV acquire infection from their
mother at or before delivery. A further 15% are infected through breast feeding. Prenatal testing for HIV
allows infected women to be reliably identified so that they can receive antiretroviral therapy and, in
countries with safe water supplies, be advised not to breast feed. These and other interventions can reduce
the risk of transmission to 5% or less. Economic evaluations of prenatal testing for HIV are reviewed and
compared in this article, and future research priorities outlined. These studies set the costs of testing and
intervention against the averted lifetime costs of paediatric infection, and generate estimates of the HIV
prevalence threshold above which there would be a net cost saving, or calculate the cost per life-year saved
given a particular prevalence. In the developed world, prenatal testing has been adopted in many countries,
and recent economic analyses broadly support this. Future research is likely to focus on the incremental
benefits of different antiretroviral regimens in lowering transmission rates still further, with or without elective
caesarean section, and the possibility that some may lead to adverse effects in uninfected infants exposed
to them in utero. Some earlier assessments in resource-poor settings concluded that prenatal testing was
unaffordable or of doubtful cost effectiveness. This negative conclusion appears to be the result of very low
estimates of the lifetime costs of paediatric HIV infection, together with developed world conceptions of pretest counselling. The demonstration that nevirapine reduces transmission risk at a low cost has transformed
the outlook, and there is hope that antiretrovirals can act prophylactically to prevent infection of the breastfed child. However, to achieve a sustained reduction in vertical transmission there may be a need to
evaluate the need for a strengthened infrastructure to deliver prenatal HIV testing and treatment, as well as
programmes to reduce HIV incidence in adults.
Akue, J. P., P. Babaki, F. Barre-Sinoussi, N. Charpak, G. de The, M. F. Rea, C. Huraux,
B. Ndiaye, H. Pratomo, N. M. Samuel, C. Wilfert, and R. Zetterstrom. 2000.
"Human immunodeficiency virus type-1: mother-to-child transmission. Meeting of
World Federation of Scientists in Erice, Italy, August 2000. Joint report of
Page 48 of 56
AIDS/Infectious Diseases PMP and Mother and Child PMP." Acta Paediatr,
89(11):1385-6.
Baleta, A. 2000. "AIDS activists take South African government to court." Lancet,
356(9231):746.
Bohlin, A. B., S. Lindgren, K. Lidman, and A. Sonnerborg. 2000. "[Mother-to-child
transmission of HIV infections. Antiviral agents and Cesarean section reduce the
risk of transmission]." Lakartidningen, 97(28-29):3275-9.
There has been a substantial decrease in maternal-infant transmission of HIV in many European and North
American countries during the past five years, from 15-25 per cent to approximately 5%. Reasons include
the prophylactic administration of zidovudine to mother and child, more effective treatment strategies leading
to decreased viral load during pregnancy, and increased use of elective Caesarean section. In developing
countries however, the vertical transmission rate of HIV is still high at 25-40 per cent. Simpler and less
expensive prophylactic regimens, such as nevirapine to mother and child at delivery and after birth,
respectively, have raised hope. Drug resistance and the risk of adverse effects of antiretroviral drugs on the
child are threats to the prevention of mother-to-infant transmission of HIV.
Brocklehurst, P. 2000. "Interventions aimed at decreasing the risk of mother-to-child
transmission of HIV infection." Cochrane Database Syst Rev, (2):CD000102.
BACKGROUND: At the end of 1998 over 33 million people were infected with the human immunodeficiency
virus (HIV) and over one million children had been infected from their mothers. OBJECTIVES: The objective
of this review was to assess what interventions may be effective in decreasing the risk of mother-to-child
transmission of HIV infection as well as their effect on neonatal and maternal mortality and morbidity.
SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register and the Cochrane
Controlled Trials Register were searched. SELECTION CRITERIA: Randomised trials comparing any
intervention aimed at decreasing the risk of mother-to-child transmission of HIV infection compared with
placebo or no treatment, or any two or more interventions aimed at decreasing the risk of mother-to-child
transmission of HIV infection. DATA COLLECTION AND ANALYSIS: Trial quality assessments and data
extraction were undertaken by the reviewer. MAIN RESULTS: Zidovudine Four trials comparing zidovudine
with placebo involving 1585 participants were included. Compared with placebo, there was a significant
reduction in the risk of mother-to-child transmission with any zidovudine (relative risk (RR) 0.54, 95%
confidence interval (CI) 0.42-0.69). There is no evidence that 'long course therapy' is superior to 'short
course therapy'. Nevirapine One trial compared intrapartum and postnatal nevirapine with intrapartum and
postnatal zidovudine in 626 women, the majority of whom breast fed their infants. Compared with
zidovudine, there was a significant reduction in the risk of mother-to-child transmission of HIV with
nevirapine (RR 0.58, 95% CI 0.40-0.83). No trials are available comparing nevirapine with placebo.
Caesarean section One trial comparing elective caesarean section with anticipation of vaginal delivery
involving 436 participants was included. Compared with vaginal delivery, there was a significant reduction in
the risk of mother-to-child transmission of HIV infection with caesarean section (RR 0.17, 95% CI 0.05-0.55).
Immunoglobulin One trial comparing hyperimmune immunoglobulin plus zidovudine with non-specific
immunoglobulin plus zidovudine involving 501 participants was included. The addition of hyperimmune
immunoglobulin to zidovudine does not appear to have any additional effect on the risk of mother-to-child
transmission (RR 0.67, 95% CI 0.29-1.55). REVIEWER'S CONCLUSIONS: Zidovudine, nevirapine and
delivery by elective caesarean section appear to be very effective in decreasing the risk of mother-to-child
transmission of HIV infection.
Castetbon, K., V. Leroy, R. Spira, and F. Dabis. 2000. "[Preventing the transmission of
HIV-1 from mother to child in Africa in the year 2000]." Sante, 10(2):103-13.
African women of childbearing age are particularly vulnerable to HIV infection, and this has led to an
increase in the number of pediatric HIV infections reported due to the risk of mother-to-child transmission
Page 49 of 56
(MTCT) of HIV during pregnancy, delivery and breastfeeding. Various approaches to preventing MTCT have
been, or are being, evaluated in developing countries, especially in Africa. New data from these trials are
becoming available and have implications for population-based intervention programs that require urgent
consideration. We performed a critical review of 18 randomized trials and other relevant studies from
developing and industrialized countries, to assess public health perspectives and to identify new research
issues. Most African results relate to trials of antiretroviral drugs (ARVs) given to mothers during the last
month of pregnancy, and for up to one week after delivery, and to the neonate during the first week of life, or
simpler and shorter regimens. They indicate that zidovudine treatment, with or without lamivudine, and
nevirapine treatment given alone, reduce transmission during the first six months of life by 30 % to 50%.
Preliminary results suggest that zidovudine treatment is effective in the long term. One randomized study
showed that the replacement of breast feeding with breast milk substitutes was effective at reducing the
overall risk of MTCT. Antiseptic disinfection and micronutrient supplementation have been shown to reduce
maternal and infant mortality and morbidity, but not the MTCT of HIV. Voluntary, confidential HIV counseling
and testing for pregnant women, a short course of peripartum ARVs and alternatives to breast feeding such
as early weaning and breast milk substitutes from birth, are currently the best means of reducing the MTCT
of HIV in Africa. Pilot programs based on these findings are currently being implemented in several African
countries. Prevention of the MTCT of HIV should also be considered as part of the wider management of
maternal and infant health during prenatal, delivery and postnatal care. Several complementary issues
require further investigation. Some results, such as the long-term efficacy of a short course of ARVs once
the mother has finished breast feeding, and the long-term safety of these treatments, require confirmation.
Further studies are required into the prevention of postnatal transmission, particularly in light of the unknown
consequences of different feeding options and the possibility of post-perinatal prophylaxis with ARVs. The
reduction of MTCT of HIV in Africa is a true challenge in efforts to control the HIV pandemic, but recent
progress in the identification of effective treatments provides some hope. Large-scale implementation of
these new treatments is required, and should provide practical information and perhaps identify more potent,
and possibly cheaper, strategies.
Clark, S. 2000. "Hope for prevention of mother-to-child transmission of HIV." Lancet,
356(9226):316.
Dabis, F. and V. Leroy. 2000. "Preventing mother-to-child transmission of HIV: practical
strategies for developing countries." AIDS Read, 10(4):241-4.
The HIV pandemic has greatly affected women of childbearing age in developing countries and, thus, their
offspring, through mother-to-child transmission (MTCT) of the virus. Scientific advances, most of them
established by randomized clinical trials, have recently led to the development of practical strategies aiming
to reduce the public health burden of MTCT of HIV. These advances came first in non-breast-feeding
populations, for example, in Thailand and, more recently, in African populations, where breast-feeding
remains the predominant mode of infant feeding. This article reviews major accomplishments in this area,
outlines practical issues for program implementation, and suggests future research needs. Short-course
zidovudine and short-course nevirapine in the peripartum period currently represent 2 valid options to
reduce MTCT of HIV in developing countries if appropriate prenatal, obstetrical, and postnatal care is
provided and if alternatives to breast-feeding are considered according to the local situation and the
mother's individual decision.
Dabis, F., V. Leroy, K. Castetbon, R. Spira, M. L. Newell, and R. Salamon. 2000.
"Preventing mother-to-child transmission of HIV-1 in Africa in the year 2000."
Aids, 14(8):1017-26.
OBJECTIVES: Various approaches to preventing mother-to-child transmission (MTCT) of HIV have recently
been, or are being, evaluated in developing countries, especially in Africa. New findings from these trials are
now becoming available, the implications of which, for population-based intervention programmes, need
urgent consideration. METHOD: A critical review of 18 randomized trials and other relevant studies from
developing and industrialized countries. RESULTS: Most African results relate to trials of antiretroviral
agents (ARV). They demonstrate efficacy in reducing transmission in the first 6 months of life with short
regimens of zidovudine (ZDV), with or without lamivudine (3TC), and nevirapine (NVP) alone. Preliminary
results suggest the long-term efficacy of zidovudine. Antiseptic and nutritional interventions have been
Page 50 of 56
shown to reduce maternal and infant mortality and morbidity but not MTCT of HIV. HIV confidential voluntary
counselling and testing for pregnant women, a short regimen of peripartum ARV with alternatives to
breastfeeding such as early weaning or breast milk substitutes from birth currently represent the best option
to reduce MTCTof HIV in Africa. However, the prevention of postnatal transmission requires further
research, particularly in view of the consequences of different feeding options and the possibility of postperinatal exposure prophylaxis of newborns with ARV. Issues relating to the implementation of currently
validated strategies are discussed.
Edgeworth, R. L. and K. E. Ugen. 2000. "Immunopathological factors for vertical
transmission of HIV-1." Pathobiology, 68(2):53-67.
With the global rise in human immunodeficiency virus-1 (HIV-1) infection in women of childbearing age,
there has also been an alarming rise in the number of mother-to-child transmissions of HIV-1. Although drug
therapies such as zidovudine as well as nevirapine have been demonstrated to significantly decrease the
incidence of vertical transmission of HIV-1, these therapeutic regimens are still not widely available in some
developing countries where maternal-to-child transmission of HIV-1 continues to occur at an alarming rate.
Therefore, the continued studies of mechanisms and correlates of vertical transmission of HIV-1 are
warranted. The current status of immunological and virological correlates of vertical transmission are
summarized in this review. In addition, information concerning recent therapeutic agents for the prevention
of HIV-1 vertical transmission is presented.
Fernandez, A. D. and D. F. McNeeley. 2000. "Management of the infant born to a
mother infected with human immunodeficiency virus type 1 (HIV-1): current
concepts." Am J Perinatol, 17(8):429-36.
Despite the use of highly active antiretroviral therapy (HAART) and the success of protocol PACTG-076 in
decreasing perinatal transmission of HIV infection in many industrialized countries, a total of 5,600,000 new
cases of HIV infection were diagnosed worldwide in 1999. Of those cases, more than 10% are children
under 15 years of age. The vast majority of pediatric HIV infection is due to perinatal transmission. More
than 95% of HIV-infected people live in the developing world. Different studies are currently being conducted
with modifications of the original PACTG-076, especially shorter courses of zidovudine (ZDV), combinations
of antiretrovirals (ZDV and 3TC), or comparison of a modified version of the standard ZDV course vs. a
single dose of nevirapine for the mother intrapartum and also for the newborn. The results of these studies
may provide more affordable, alternative regimens to prevent maternal-to-child HIV-1 transmission for
developing countries than the PACTG-076 protocol. It is very important that physicians and physician
extenders (nurse practitioners and physician assistants) caring for infants born to HIV-infected mothers have
an understanding of the pathophysiology of vertical HIV-1 infection transmission. They should be familiar
with the conditions associated with an increased risk of transmission, interventions available to decrease this
risk, current medications, and laboratory resources.
Hankins, C. 2000. "Preventing mother-to-child transmission of HIV in developing
countries: recent developments and ethical implications." Reprod Health Matters,
8(15):87-92.
Various regimens of antiretroviral (ARV) therapy during pregnancy and labour have been found to be
effective in reducing the risk of mother-to-child transmission of HIV. Cost and late identification of women
with HIV infection during pregnancy in many developing countries have been the impetus to study
inexpensive, short-course ARV regimens. Recently, it was shown that a single dose of nevirapine given
orally once during labour to the mother and once to the infant greatly reduces the risk of HIV transmission.
As a result, it has been proposed that in high HIV prevalence areas, this drug regimen be offered routinely to
all pregnant women and their infants, without the need for an HIV test. This is seen as a cost-effective
alternative to trying to make voluntary HIV testing and counselling universally available to pregnant women,
which would require improved antenatal uptake and care, high uptake of HIV testing and high rates of return
to learn results before women could make decisions regarding ARV prophylaxis. The ethical dilemmas
arising from both these options are currently under debate, against a backdrop of concerns about
breastfeeding and breastmilk substitutes, what to do about the increasing numbers of AIDS orphans and
how to prevent HIV transmission to women in the first place.
Page 51 of 56
Hayashi, T. 2000. "[New therapy reduces AIDS passed to fetuses and costs less]."
Yakugaku Zasshi, 120(8):683-7.
The AIDS clinical group protocol of zidovudine (AZT) prophylaxis regimen for HIV-1-infected pregnant
women and their babies has been associated with a decrease in vertical HIV-1 transmission in nonbreastfeeding women in developmental countries. However, scientists furthermore compared the safety and
efficacy of short-course nevirapine or AZT during labour and the first week of life. In an advancement that
promises to significantly reduce the incidence of AIDS in children in developing countries, scientists have
found a simple new way with nevirapine to prevent mother-to-child transmission of the AIDS virus that also
is less costly and markedly more effective than the standard therapy with AZT in the third world. The more
practical therapy comes from substituting one marketed drug, nevirapine, for the standard drug, AZT. The
cost for the two doses of nevirapine was $4, compared with $268 for AZT regimen now used in developing
countries and $815 for the much longer and more complicated course used in the U.S. and other developing
countries. It is proposed that wide-scale use of nevirapine in developing countries could potentially prevent
300,000 to 400,000 newborns each year from beginning life infected with HIV.
Mirochnick, M., D. F. Clarke, and A. Dorenbaum. 2000. "Nevirapine: pharmacokinetic
considerations in children and pregnant women." Clin Pharmacokinet, 39(4):28193.
Nevirapine is a potent non-nucleoside inhibitor of HIV-1 reverse transcriptase. It is effective when used as
part of combination therapy to treat HIV-1-infected individuals and as monotherapy for prevention of motherto-child HIV-1 transmission. Nevirapine pharmacokinetics are characterised by rapid absorption and
distribution, followed by prolonged elimination. Nevirapine is generally well tolerated. The most common
toxicity is rash, which is usually mild and self-limiting. The primary route of nevirapine elimination is through
metabolism by the cytochrome P450 enzyme system. Nevirapine elimination accelerates during long term
administration because of autoinduction of the enzymes involved in its elimination pathway. The
recommended regimen for adults is nevirapine 200mg once daily for 2 weeks, followed by 200mg twice
daily. Nevirapine elimination is prolonged in pregnant women during labour and in newborns. A regimen of a
single 200mg oral dose administered to the mother during labour and a single 2 mg/kg dose administered to
the newborn at 48 to 72 hours after birth maintains serum nevirapine concentrations above 100 microg/L (10
times the in vitro 50% inhibitory concentration against wild-type HIV-1) throughout the first week of life. This
limited regimen has been shown to be extremely well tolerated and to reduce mother-to-child transmission
by nearly 50% in mothers and infants receiving no other antiretrovirals. There are few data describing the
safety and pharmacokinetics of nevirapine during long term use in pregnancy. In children, nevirapine
elimination accelerates during the first years of life, reaching a maximum at around 2 years of age, followed
by a gradual decline during the rest of childhood. Children should receive 4 mg/kg once daily for the first 2
weeks of therapy, followed by 7 mg/kg doses twice daily if below the age of 8 years or 4 mg/kg twice daily if
older than 8 years. Alternatively, children may receive 150 mg/m2 across all ages, once daily for the first 2
weeks of therapy followed by the same dose twice daily.
Thorne, C. and M. L. Newell. 2000. "Epidemiology of HIV infection in the newborn."
Early Hum Dev, 58(1):1-16.
Vertical transmission of HIV infection can take place in utero, during delivery and postnatally through
breastfeeding, with about three-quarters of infections occurring around the time of delivery in nonbreastfeeding populations. In Europe, in the absence of specific interventions, the vertical transmission rate
was 15-20%. High maternal load is the major risk factor for both intra-uterine and intra-partum mother-tochild transmission. Prematurity is the most common adverse neonatal outcome associated with maternal
HIV infection. Earlier diagnosis of paediatric HIV infection than previously available is now possible with
virological tests, particularly HIV DNA polymerase chain reaction. An estimated one fifth of infected children
will have been diagnosed with AIDS or have died by 12 months of age, rising to a third by 6 years of age.
Surgical and therapeutic interventions are effective in reducing vertical transmission risk, in addition to the
avoidance of breastfeeding. Caesarean section delivery before labour and before rupture of membranes
approximately halves the risk of transmission, while prophylactic zidovudine therapy according to the
ACTG076 regimen reduces transmission by up to two-thirds, transmission is reduced even further with both
interventions. Trials of short-course zidovudine regimens show their effectiveness in reducing vertical
Page 52 of 56
transmission, in breastfeeding and non-breastfeeding populations. Nevirapine has been shown to be
significantly more effective than short course zidovudine regimens in breastfeeding populations, but is still
under evaluation in non-breastfeeding populations additionally receiving routine anti-retroviral prophylaxis.
Reports of a small number of serious adverse events in uninfected children exposed in utero or neonatally to
antiretroviral therapy need further investigation. Trials of vitamin A supplementation to reduce vertical
transmission have had negative results, while the effectiveness of vaginal lavage and passive immune
therapy in reducing vertical transmission remains uncertain.
1999. "Study offers hope for Africa's next generation." World, (No 101):4-5.
1999. "There's no excuse for babies to be born today infected with HIV." AIDS Alert,
14(11):121-3.
1999. "Perinatal transmission." AIDS Policy Law, 14(14):12.
1999. "Simpler regimens for preventing mother-to-child HIV transmission." Proj Inf
Perspect, (28):20.
Guay, L. A., P. Musoke, T. Fleming, D. Bagenda, M. Allen, C. Nakabiito, J. Sherman, P.
Bakaki, C. Ducar, M. Deseyve, L. Emel, M. Mirochnick, M. G. Fowler, L.
Mofenson, P. Miotti, K. Dransfield, D. Bray, F. Mmiro, and J. B. Jackson. 1999.
"Intrapartum and neonatal single-dose nevirapine compared with zidovudine for
prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda:
HIVNET 012 randomised trial." Lancet, 354(9181):795-802.
BACKGROUND: The AIDS Clinical Trials Group protocol 076 zidovudine prophylaxis regimen for HIV-1infected pregnant women and their babies has been associated with a significant decrease in vertical HIV-1
transmission in non-breastfeeding women in developed countries. We compared the safety and efficacy of
short-course nevirapine or zidovudine during labour and the first week of life. METHODS: From November,
1997, to April, 1999, we enrolled 626 HIV-1-infected pregnant women at Mulago Hospital in Kampala,
Uganda. We randomly assigned mothers nevirapine 200 mg orally at onset of labour and 2 mg/kg to babies
within 72 h of birth, or zidovudine 600 mg orally to the mother at onset of labour and 300 mg every 3 h until
delivery, and 4 mg/kg orally twice daily to babies for 7 days after birth. We tested babies for HIV-1 infection
at birth, 6-8 weeks, and 14-16 weeks by HIV-1 RNA PCR. We assessed HIV-1 transmission and HIV-1-free
survival with Kaplan-Meier analysis. FINDINGS: Nearly all babies (98.8%) were breastfed, and 95.6% were
still breastfeeding at age 14-16 weeks. The estimated risks of HIV-1 transmission in the zidovudine and
nevirapine groups were: 10.4% and 8.2% at birth (p=0.354); 21.3% and 11.9% by age 6-8 weeks
(p=0.0027); and 25.1% and 13.1% by age 14-16 weeks (p=0.0006). The efficacy of nevirapine compared
with zidovudine was 47% (95% CI 20-64) up to age 14-16 weeks. The two regimens were well tolerated and
adverse events were similar in the two groups. INTERPRETATION: Nevirapine lowered the risk of HIV-1
transmission during the first 14-16 weeks of life by nearly 50% in a breastfeeding population. This simple
and inexpensive regimen could decrease mother-to-child HIV-1 transmission in less-developed countries.
Henry, K. 1999. "Affordable drug offers hope for preventing mother-to-child transmission
of HIV." Impact HIV, 1(2):15-21.
Kasper, T. 1999. "Unequal care sustains vertical transmission rate." GMHC Treat
Issues, 13(2):11-2.
Page 53 of 56
Leroy, V. and F. Dabis. 1999. "[Reduction of mother-child transmission of HIV infection
in Africa: from clinical research to public health programs]." Med Trop (Mars),
59(4 Pt 2):456-64.
More and more African women are infected by HIV. As a result the mother-to-child transmission (MCT) rate
is rising. Various prevention techniques have been assessed in randomized clinical trials in Africa but results
need to be discussed to understand the full implications for prevention programs. To gain insight into this
issue, we reviewed 11 randomized trials conducted in Africa and several other studies from developed
countries. Trials using antiretroviral (ARV) drugs demonstrated good results for prevention of MCT in the first
six months of life using abbreviated regimens involving either zidovudine (with or without lamivudine) or
nevirapine alone. Preliminary results suggest long-term effectiveness of zidovudine. Antiseptic and
nutritional interventions have demonstrated some efficacy in reducing maternal and newborn morbidity and
mortality but have no effect on MCT rate. Confidential, voluntary HIV screening and counseling of pregnant
women and short-course ARV treatment during the perinatal period associated with alternatives to breastfeeding such as early weaning or replacement of breast milk at birth are now the best methods to reduce
MCT. Prevention of postnatal transmission will require further study in particular with regard to effects of
different methods of feeding and post-exposure prophylaxis using ARV drugs in newborns. Management of
HIV-infected children must remain a high priority. Implementation of currently available strategies is now
under discussion.
MacDougall, D. S. 1999. "Global strategies for the prevention of HIV transmission from
mothers to infants: the second conference." J Int Assoc Physicians AIDS Care,
5(12):52-7, 62.
Okereke, C. S. 1999. "Management of HIV-infected pregnant patients in malariaendemic areas: therapeutic and safety considerations in concomitant use of
antiretroviral and antimalarial agents." Clin Ther, 21(9):1456-96; discussion 14278.
Chemotherapy in pregnancy is an intricate process requiring prudent use of pharmacologic agents. Malarial
infection during pregnancy is often fatal, and prophylaxis against the causative parasite necessitates rational
therapeutic intervention. Various agents have been used for prophylaxis against malaria during pregnancy,
including chloroquine, mefloquine, proguanil, pyrimethamine, and pyrimethamine-sulfadoxine. Use of these
agents has been based on a risk-benefit criterion, without appropriate toxicologic or teratologic evaluation.
Some of the aforementioned prophylactic agents have been shown to alter glutathione levels and may
exacerbate the oxidation-reduction imbalance attendant on HIV infection. HIV-infected patients traveling to
or residing in malaria-endemic areas require protection from malarial infection to avoid placing themselves in
double jeopardy. Zidovudine (AZT) is recommended for the prevention of vertical transmission of HIV-1 from
mother to child. Other agents, such as lamivudine alone or in combination with AZT, nevirapine, or the HIV-1
protease inhibitors, are either being considered or are currently undergoing trials for use in preventing
vertical transmission of HIV-1 or managing HIV infection in infants and children. Although the potential for
antimalarial agents to cause congenital malformations is low when they are used alone, their ability to cause
problems when combined with antiretroviral drugs needs to be evaluated. In developing countries that have
high birth rates, a high endemicity of malaria, and alarming rates of new cases of HIV, prophylaxis against
both diseases with combination agents during pregnancy is a challenge.
Piot, P. and A. Coll-Seck. 1999. "Preventing mother-to-child transmission of HIV in
Africa." Bull World Health Organ, 77(11):869-70.
Vazquez, E. 1998. "Mother-to-child transmission." Posit Aware, 9(1):15.
Page 54 of 56
Cadman, J. 1997. "Rapid advances in preventing vertical transmission." GMHC Treat
Issues, 11(7-8):25-31.
de Jong, M. D., R. J. de Boer, F. de Wolf, N. A. Foudraine, C. A. Boucher, J. Goudsmit,
and J. M. Lange. 1997. "Overshoot of HIV-1 viraemia after early discontinuation
of antiretroviral treatment." Aids, 11(11):F79-84.
OBJECTIVE: To determine whether, as predicted by predator-prey dynamics, early withdrawal of
antiretroviral therapy, i.e. when the number of CD4+ lymphocytes is still elevated, results in an overshoot of
HIV-1 viraemia due to infection of increased numbers of available target cells at that time. DESIGN AND
METHODS: Five HIV-1-infected individuals were identified who discontinued antiretroviral therapy for
various reasons after 8-19 days, and from whom stored serum samples obtained before, during, and shortly
after treatment were available for measurement of HIV-1 RNA load. A mathematical model was designed to
assess whether increased target cell availability could quantitatively explain the clinical observations.
RESULTS: After therapy withdrawal, increases in the HIV-1 RNA load to levels exceeding pretreatment
values by log10 0.6-1.5 copies/ml were observed after 2-17 days in all four of the individuals who had
treatment-induced increases in CD4+ cell counts at the time of therapy withdrawal. Increases in viraemia
were maximal within a few days, and subsequently seemed to wane until the pretreatment equilibrium
between virus and its target cells was attained. Mathematical modelling confirms that these transient
increases in viraemia can be explained by increased availability of target cells at the time of therapy
withdrawal. CONCLUSIONS: Transient rises in HIV-1 viraemia do occur following early therapy withdrawal.
These rises especially warrant consideration in short-term antiretroviral regimens for prevention of motherto-child transmission, as are being studied in developing countries, since they could result in an increased
transmission risk during the post-partum period through breast-feeding. This possibility needs to be
investigated urgently.
James, J. S. 1997. "Pregnant women eligible for single-dose nevirapine study." AIDS
Treat News, (No 280):4.
1996. "Researcher predicts dramatic drop in infections in babies." AIDS Policy Law,
11(13):4.
Benson, M. and M. Shannon. 1995. "Nevirapine: ethical dilemmas and care for HIVinfected mothers." Focus, 10(7):5-6.
Hoernle, E. H. and T. E. Reid. 1995. "Human immunodeficiency virus infection in
children." Am J Health Syst Pharm, 52(9):961-79.
The transmission, diagnosis, and clinical manifestations of human immunodeficiency virus (HIV) infection in
children up to 13 years of age are reviewed, and maintenance and prophylactic drug therapies for these
patients are discussed. HIV can be transmitted from mother to infant in utero, during delivery, or through
breast milk. Perinatal transmission accounts for almost 90% of all pediatric HIV infections. HIV infection can
be diagnosed with HIV culturing, polymerase chain reaction testing, the enzyme-linked immunosorbent
assay, the Western blot antibody assay, or the p24 core-antigen assay. Testing should begin as soon as
possible after the at-risk child reaches one month of age. CD4+ lymphocyte counts are also used in
diagnosis and monitoring. The median age at diagnosis of AIDS in children with perinatally acquired HIV
infection is 12-24 months. Among the many possible clinical features are Pneumocystis carinii pneumonia
(PCP), cytomegalovirus infection, failure to thrive, encephalopathy, recurrent bacterial infection, thrush,
lymphoid interstitial pneumonitis, lymphadenopathy, pancreatis, hepatitis, anemia, and thrombocytopenia.
Zidovudine is considered the drug of choice for initial therapy in HIV-infected children and is indicated for
asymptomatic infection, early symptomatic disease, and advanced disease. However, new research is
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questioning the role of zidovudine monotherapy. Didanosine is the only agent with FDA-approved labeling
for use as second-line therapy in children who do not respond to or become resistant to zidovudine. Agents
under investigation for pediatric use are zalcitabine, stavudine, lamivudine, and nevirapine. Drug
combinations, such as zidovudine plus didanosine, are also being examined. Zidovudine appears to reduce
the rate of maternal transmission of HIV. Agents used prophylactically against PCP in children are
trimethoprim-sulfamethoxazole, dapsone, and inhaled or i.v. pentamidine. HIV-infected children should also
received prophylaxis against recurrent bacterial infections. The standard pediatric immunization schedule is
used, but inactivated injectable poliovirus vaccine must be given instead of the live oral vaccine. Zidovudine
remains the first-line agent for treating HIV infection in children. Alternatives are available for those who do
not respond to zidovudine.
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