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Antiretroviral treatment and prevention of peripartum and postnatal HIV transmission in West Africa: evaluation of a two-tiered approach
Global Health Sciences Literature Digest
Published November 5, 2007
Journal Article

Tonwe-Gold B, Ekouevi DK, Viho I, Amani-Bosse C, Toure S, Coffie PA, et al. Antiretroviral treatment and prevention of peripartum and postnatal HIV transmission in West Africa: evaluation of a two-tiered approach. PLoS Med 2007 Aug 21;4(8):e257.


To evaluate the short-term and long-term effectiveness of a two-tiered prevention of mother-to-child HIV transmission (PMTCT) strategy. Depending on their CD4 T cell count and World Health Organization (WHO) stage, women were given either highly active antiretroviral therapy (HAART) or short-course antiretroviral (scARV) regimens for PMTCT.

Study Design

Observational cohort study.


Two antenatal clinics in two low-income urban districts of Abidjan, C�te d'Ivoire that were participating in the MTCT-Plus Initiative care and treatment program.


The study population included all HIV-infected pregnant women and their live-born infants enrolled in the MTCT-Plus Initiative between August 2003 and April 2005. They were followed until a final pediatric HIV status could be determined.


The MTCT-Plus Initiative is a multi-country, comprehensive HIV care and treatment program for pregnant and postpartum women and their families and built on existing PMTCT services, which includes the provision of HAART to the woman, her partner, and her children. Upon enrollment to this study, all participants were screened for HAART eligibility based on WHO clinical stage (accounting for the changes in the 2005 WHO PMTCT guidelines), CD4 count, medical contraindications, and major barriers to adherence. Pregnant women who were not eligible for HAART received validated scARV prophylactic regimens. All infants received zidovudine (ZDV) syrup for seven days and single-dose nevirapine (sdNVP) syrup on day three of life, irrespective of the maternal drug regimen. Women either used breast milk substitutes, if feasible and affordable following WHO guidelines, or were encouraged to practice exclusive breastfeeding for a maximum of six months, and initiate early weaning from four months onward. Cesarean section was only performed for emergencies. Participants were seen at baseline, weekly for eight weeks, and monthly thereafter. CD4 counts and percentages were determined by flow cytometry at enrollment and every six months after the initiation of treatment. Plasma HIV-RNA viral load (VL) testing for the early diagnosis of pediatric HIV infection was performed using quantitative real-time polymerase chain reaction. All infants were tested at four weeks of age, and if positive, confirmed with repeat VL testing at six weeks (termed peripartum infection). Infants with a negative VL test at four weeks of age were subsequently tested at 12 months by rapid antibody testing. If this antibody test was positive, a second test was performed at 15 months for confirmation (termed postnatal infection). The HIV status of the children who stopped follow-up just after being tested HIV antibody-positive at 12 months or who had ceased breastfeeding under the age of two months was confirmed by VL testing.

Primary Outcomes

Rates of HIV transmission and HIV-free survival at four weeks and 12 months; maternal and infant adverse events.


Study population characteristics: A total of 261 pregnant women with confirmed HIV-1 infection were enrolled in the study. The overall median maternal age was 27 years (interquartile range [IQR] 24-31 years), and the median gestational age at the time of enrollment was 30 weeks (IQR 25-33 weeks). The median CD4 count was 338 cells/mm3 (IQR 206-488 cells/mm3) and 44 (17.6%) were classified as WHO clinical stage 3 or 4. Three of the original 261 women were lost to follow-up, and eight delivered before an ARV regimen could be initiated. The remaining 250 women were prescribed ARVs before and/or during delivery: 107 (43%) received a HAART regimen and 143 (57%) received scARVs. Of the women on HAART, 102 received ZDV, lamivudine (3TC), and NVP. Five women were prescribed stavudine (d4T), 3TC, and NVP. HAART was initiated at a median of 30 weeks gestation (IQR 27-33 weeks), and the median duration on HAART until delivery was 74 days (48-91 days). Of the 93 women treated with HAART > 1 month before delivery, 91% reported complete adherence in the previous seven days. Among the women who received scARV for PMTCT, the median gestational age at prophylaxis initiation was 34 weeks (IQR 32-36 weeks), and the median number of days on scARV was 46 days (IQR 31-65 days); 103 women received sc(ZDC+3TC) with sdNVP during labor, 26 scZDV with sdNVP, and 14 sdNVP alone. Pregnancy outcomes were not available for nine women due to spontaneous abortion (three in the HAART group and one in the scARV for PMTCT group) and loss to follow-up. Among the 241 women who had pregnancy outcomes for the analysis, 172 (71.3%) initiated breastfeeding at birth (62 in the HAART group and 110 in the scARV for PMTCT group). The overall median duration of breastfeeding was 5.4 months (IQR 4.0-6.8 months) and was slightly longer in the scARV for PMTCT group than in the HAART group (5.8 vs. 4.6 months; p=0.01). Effectiveness of ARV regimens: Excluding the second child of five multiple births, there were 241 pregnancy outcomes for analysis. Four neonates in the HAART group and six in the scARV for PMTCT group were stillborn, and three infants died in each group in the first week of life before HIV testing could be done. A total of 12 infants were diagnosed as HIV-infected during the study: five by the age of four weeks, three more by the age of three months, and the remaining four by the age of 12 months. Overall, the rate of peripartum HIV transmission was 2.2% (95% confidence interval [CI] 0.3%-4.2%): 1.0% (95% CI 0.0%-3.1%) in the HAART group and 3.1% (95% CI 0.1%-6.1%) in the scARV for PMTCT group. The cumulative rate at 12 months was 5.7% (95% CI 2.5%-9.0%): 3.3% (95% CI 0.0%-6.9%) in the HAART group and 7.5% (95% CI 2.8%-12.3%) in the scARV for PMTCT group (p=0.18). No statistically significant difference was found according to the infant-feeding practice (p=0.48). Only low birth weight (<2,500g) was associated with HIV acquisition (adjusted hazard ratio [HR] 5.63, 95% CI 1.62-19.49, p=0.006). Postnatal transmission: Subsequent diagnosis was not possible for 11 children lost to follow-up and 10 who died (six in the HAART group and four in the scARV for PMTCT group). Definitive diagnoses could not be made for five children who were antibody negative but still breastfeeding by 12 months. A total of 191 infants (87 in the HAART group and 104 in the scARV for PMTCT group) were analyzed for postnatal transmission, of whom 138 were breastfed (52 in the HAART group and 96 in the scARV for PMTCT group). The median duration on HAART in breastfeeding women was 14.9 months (IQR 14.5-16.2 months) when the final pediatric HIV status was ascertained. Overall, four infants had a confirmed postnatal infection (2.3% [95% CI 0.8%-7.3%]: 1/52 infants (1.9% [95% CI 0.04%-10.2%]) breastfed for a median of 4.7 months (IQR 3.3-6.3 months) in the HAART group, and 3/86 infants (3.5% [95% CI 0.7%-9.9%]) breastfed for a median of 5.7 months (IQR 4.3-7.1 months) in the scARV for PMTCT group. Twelve-month HIV-free survival and death by maternal ARV regimen: The overall probability of infant death or infection with HIV was 4.3% (95% CI 1.7%-7.0%) at age four weeks and 11.7% (95% CI 7.5%-15.9%) at 12 months; 11.2% (95% CI 5.0%-17.4%) among infants born to HAART-treated women, and 12.1% (95% CI 6.4%-17.9%) among infants born to mothers treated with scARV for PMTCT (p=0.90). Low birth weight (adjusted HR=3.71 [95% CI 1.53-9.03], p=0.004) and female sex (adjusted HR=0.35 [95% CI 0.14-0.88], p=0.035) were associated with the occurrence of HIV infection or death. A total of 18 infant deaths were reported: 10/99 in the HAART group (10.1%) and 8/132 (6.0%) in the scARV for PMTCT group. Adverse events: Nine (8.4%) of the 107 women receiving HAART developed adverse events significant enough to change ARVs, and all resolved with drug change. No women receiving scARV for PMTCT required drug changes. The frequency of perinatal deaths was comparable in the HAART and scARV for PMTCT groups (6.7% vs. 5.6%, p=0.80). The only significant difference between the infants in the two groups was a higher proportion of low birth weight in neonates whose mothers received HAART (26.3% vs. 12.4%, p<0.001).


The authors conclude that a two-tiered approach to PMTCT was safe during pregnancy and highly effective for the prevention of peripartum and postnatal transmission in a resource-constrained African setting. They also note a further benefit of access to HAART for pregnant women who need treatment for their own health. While further investigations in other larger or pooled studies are needed to further explore the balance of benefits and risks related to HAART in breast-feeding mothers, these results provide evidence supporting the most recent WHO PMTCT guidelines.(2)

Quality Rating

According to the Newcastle-Ottawa quality assessment scale for cohort studies, this study would receive a rating of high quality. Notably, retention and adherence rates are high. The authors mention a main limitation of small sample size, thus affecting the precision of some MTCT rates and the power to fully perform statistical comparisons between groups. This study was not designed to compare HAART to scARV directly, because the women who received HAART had more advanced HIV infection. Comparisons between groups should, therefore, be interpreted with caution.

In Context

The rate of peripartum MTCT was very low (1.0%) and similar to rates reported from industrialized countries,(3,4) despite a later identification of HIV infection during pregnancy and a relatively short duration of HAART prior to delivery. A similar rate of 1.2% was also seen in the DREAM cohort in Mozambique, in which all women received HAART starting at 25 weeks gestation, irrespective of clinical or immunological staging.(5)

Programmatic Implications

This study shows the feasibility of implementing both scARV regimens and HAART for PMTCT, and confirms the efficacy of WHO recommendations in a real-world setting. While the rates of adverse events were relatively low, the study indicates that close monitoring of pregnant women on HAART is necessary. The study does not address the potential for scARVs in pregnancy to cause a drug-resistant virus that may compromise future treatment options for the mother, especially with sdNVP. Additionally, the reason for low birth weight in some babies born to mothers on HAART is unclear. It may be because the women who needed HAART had more severe health problems from their HIV, or it may be a result of the HAART itself. Further research in this area is needed.


  1. Rouet F, Ekouevi DK, Inwoley A, Chaix ML, Burgard M, et al. Field evaluation of a rapid human immunodeficiency virus (HIV) serial serologic testing algorithm for diagnosis and differentiation of HIV type 1 (HIV-1), HIV-2, and dual HIV-1-HIV-2 infections in West African pregnant women. J Clin Microbiol 2004 Sep;42(9):4147-53.
  2. WHO (2006) Antiretroviral drugs for treating pregnant women and preventing HIV infection in infants in resource-limited settings: Towards universal access.
  3. European Collaborative Study Group. Mother-to-child transmission of HIV infection in the era of highly active antiretroviral therapy. Clin Infect Dis 2005;(40):458-645. No abstract available.
  4. Cooper ER, Charurat M, Mofenson L, Hanson IC, Pitt J, Diaz C, et al. Combination antiretroviral strategies for the treatment of pregnant HIV-1-infected women and prevention of perinatal HIV-1 transmission. J Acquir Immune Defic Syndr 2002 Apr 15;29(5):484-94.
  5. Marazzi MC, Germano P, Liotta G, Guidotti G, Loureiro S, da Cruz Gomes A, et al. Safety of nevirapine-containing antiretroviral triple therapy regimens to prevent vertical transmission in an African cohort of HIV-1-infected pregnant women. HIV Med 2006 Jul;7(5):338-44.