Ekouevi D, Coffie P, Benaud B, et al. Antiretroviral therapy in pregnant women with advanced HIV disease and pregnancy outcomes in Abidjan, Cote d'Ivoire. AIDS 2008;22:1815-20.
To evaluate pregnancy outcomes in women with advanced HIV disease who were treated either with short-course antiretroviral therapy to prevent mother-to-child transmission (PMTCT) of HIV or with highly active antiretroviral therapy (HAART) during pregnancy in Abidjan, Côte d'Ivoire
Observational cohort study conducted within two sequential PMTCT programs located in the same antenatal clinics in Abidjan: the Ditrame Plus Study, March 2001-July 2003,(1) and the MTCT-Plus Program, August 2003-August 2007.(2)
Antenatal clinics in Abidjan, Côte d'Ivoire
Women eligible for HAART were included in the analysis. Of the 774 women in the Ditrame Plus Study, 190 were included and of the 514 women in the MTCT-Plus Program, 168 were included. In the Ditrame Plus Study, 8 were lost to follow-up and 7 were gemellary (i.e. had twins). In the MTCT-Plus Program, 7 were not on HAART, 8 were on HAART less than 28 days, and 2 were gemellary. The median maternal age at enrollment was 28 years (interquartile range (IQR) 25-32), median CD4 cell count was 179 cells/?L (IQR 120-252), and the median maternal body mass index (BMI) at delivery was 23.8 kg/m2 (IQR 21.8-26.3).
In the Ditrame Plus Study, HAART was not yet available for pregnant women, so for PMTCT they received an intrapartum single dose of nevirapine (NVP) after short-course ZDV (scZDV) initiated at 26 weeks of gestation or sc(ZDV+lamivudine (3TC)) initiated at 32 weeks of gestation until 3 days postpartum. The MTCT-Plus Program included women who were on HAART before pregnancy and pregnant women who met the eligibility criteria (WHO clinical stage 2 or 3 and CD4 cell count of <350 cells/µL, or WHO stage 4 or CD4 cell count of <200 cells/µL). The women in the HAART group received HAART (ZDV or stavudine (d4T) + 3TC + NVP) antepartum and continued it in labor and after delivery. The most common antiretroviral regimen used was ZDV+3TC+NVP (87%) in the HAART group and ZDV+sdNVP (54.2%) in the PMTCT group. The median duration on HAART was 11.7 weeks, and the median exposure time to short-course antiretroviral drug (sc-ART) prophylaxis was 4.9 weeks.
In both the PMTCT group and the HAART group, infants received ZDV syrup for 7 days + sdNVP (single-dose nevirapine) syrup on day 2 or 3. In both groups, women were counseled either to replacement feed or to practice exclusive breastfeeding for 4 to 6 months. The breastmilk substitutes were free for participants in the PMTCT group and were purchased by participants in the HAART group.
Primary outcomes were pediatric HIV-1 infection, infant mortality, stillborn infants, and low birth weight (LBW). Pediatric HIV-1 infection was measured by the plasma HIV-1 RNA viral load using a quantitative real-time reverse transcriptase polymerase chain reaction (PCR) technique targeted in the HIV-1 LTR gene. Stillborn was defined as the death of a fetus at any time after pregnancy week 20. Infant mortality was defined as born-alive infants who died before their first birthday. Low birth weight and VLBW were defined as birth weight of >2500 g and >2000 g, respectively, and collected at delivery in the maternity ward by the midwife, who was unaware of the women's HIV status and antiretroviral regimen. Maternal sociodemographic, clinical, and biological characteristics were recorded at enrollment.
Of the 305 infants tested for HIV, 28 were found to be infected with the virus at 12 months (Kaplan-Meier estimate 9.6%, 95% confidence interval (CI) 6.7-13.7). In the HAART group, 2.3% had become infected (95% CI 0.7-6.9) and in the PMTCT group, 16.1% had become infected (95% CI 11.2-22.9%). Among 326 infants, the overall stillbirth rate was 3.1% (95% CI 1.5-5.6) with no significant difference between the groups. Of 309 infants, 52 (16.8%) had LBW, with a significantly higher proportion in the HAART group (22.3% vs. 12.4%; P=0.020). Multivariable logistic regression analyses found that HAART initiated before pregnancy (adjusted odds ratio [aOR] 2.88, 95% CI 1.10-7.51) and during pregnancy (aOR 2.12, 95% CI 1.15-4.65) and maternal BMI (<25 kg/m2) (aOR 2.43, 95% CI 1.20-4.91) were associated with LBW. The rate of VLBW was similar between groups (P=0.974). Although 65% of the women in the HAART group breastfed for a median of 4.7 months (IQR 3.3-6.3), 48% of women in the PMTCT group breastfed for a median 4.3 months (IQR 3.5-6.5). Neither LBW (aOR 1.5, P=0.38) nor maternal exposure to HAART (aOR 1.1, P=0.85) was statistically associated with infant mortality in HIV-uninfected infants. Using the Cox model and adjusting for feeding practices, LBW, exposure to HAART regimens, and maternal characteristics at enrollment revealed that the only factor associated with infant mortality was pediatric HIV infection (aOR 11.9, 95% CI 4.8-29.5).
The authors conclude that HAART-eligible pregnant women with advanced HIV disease demonstrated a very low rate of mother-to-child HIV transmission (2.3%) compared with HAART-eligible women who received short-course PMTCT regimens (16.1%). At the same time, the frequency of LBW was significantly higher in the HAART group compared with the PMTCT group, and no difference in infant mortality was associated with treatment regimen.
According to the Newcastle-Ottawa quality assessment scale, the women were representative of the community because all HIV-infected women were referred for enrollment in one of the two PMTCT programs in the same clinical sites and were in care by the same clinical teams. Because two sequential cohorts were compared, the authors were unable to account for changes in HIV care over time. Possible confounding variables, such as smoking, alcohol, and drug abuse, which contribute to poor birth outcomes, were not measured. Outcomes were biologically assessed and follow-up was good in both groups, although 1-year follow-up for the HAART group was based on Kaplan-Meier estimates. Not all children received HIV testing. The authors suggest that their study may have been limited by their inability to study preterm delivery (PTD) rates because the majority of HIV-infected women did not know the date of their last menstruation. Authors also were unable to study the duration of HIV exposure and LBW.
Limited data exist regarding HAART and infant outcomes in Africa. Although a study in the United Kingdom(3) and a study in the United States(4) found significant LBW among infants exposed to HAART, other studies from the United Kingdom, the United States, Europe, and Latin America have not found this association.(5) Similarly, there have been studies in Europe and the United Kingdom that have reported an increased risk of PTD among women receiving HAART during pregnancy;(4,6) conversely, studies from the United States,(5) Latin America, and the Caribbean,(7) as well as a recent meta-analysis of 14 perinatal studies,(8,9) did not show any significant association. This is an important study with regards to the effect of HAART on women and infants in Abidjan, Côte d'Ivoire.
Pregnant women on HAART were significantly less likely to transmit HIV to their infants compared with women taking an intrapartum single dose of nevirapine after short-course NDV.
- Dabis F, Bequet L, Ekouevi D, et al. Field efficacy of zidovudine, lamivudine and single-dose nevirapine to prevent peripartum HIV transmission. AIDS 2005;19:309-18.
- Tonwe-Gold B, Ekouevi DK, Viho I, A, et al. Antiretroviral treatment and prevention of peripartum and postnatal HIV transmission in West Africa: evaluation of a two-tiered approach. PLoS Med 2007;4:e257.
- Townsend CL, Cortina-Borja M, Peckham CS, Tookey PA. Antiretroviral therapy and premature delivery in diagnosed HIV-infected women in the United Kingdom and Ireland. AIDS 2007;21:1019-26.
- Tuomala RE, Shapiro DE, Mofenson LM, et al. Antiretroviral therapy during pregnancy and the risk of an adverse outcome. N Engl J Med 2002; 346:1863-70.
- Szyld EG, Warley EM, Freimanis L, et al. Maternal antiretroviral drugs during pregnancy and infant low birth weight and preterm birth. AIDS 2006;20:2345-53.
- Grosch Woerner I, Puch K, Maier RF, et al. Increased rate of prematurity associated with antenatal antiretroviral therapy in a German/Austrian cohort of HIV-1-infected women. HIV Med 2008;9:6-13.
- Kourtis AP, Schmid CH, Jamieson DJ, Lau J. Use of antiretroviral therapy in pregnant HIV-infected women and the risk of premature delivery: a meta-analysis. AIDS 2007;21:607-15.
- Patel D, Thorne C, Newell ML. Use of antiretroviral therapy in pregnant HIV-infected women and the risk of premature delivery: a meta-analysis. AIDS 2007;21:1656-7. Response to Kourtis et al. Author reply 1657-8.
- European Collaborative Study. Exposure to antiretroviral therapy in utero or early life: the health of uninfected children born to HIV-infected women. J Acquire Immune Defic Syndr 2003;32:380-7.