The impact of in-utero antiretroviral therapy (ART) exposure on infant outcomes in Johannesburg, South Africa

Background: There is conflicting evidence, predominantly from developed countries, about in-utero protease inhibitor exposure and birth outcomes.We investigated the impact of ART exposure on birth weight and gestational age among infants of a population of South African women with advanced HIV disease. Methods: 1950 women with advanced HIV attending antenatal antiretroviral clinics in Johannesburg from April 2004 to July 2008 were included. Gestation and birth weight of infants exposed to ART during pregnancy (ART-exposed) were compared with those without ART exposure and CD4< 250 cells/mm3. Effects of different ART regimens were;assessed and ART exposure was categorized as early (initiation before 28 weeks) and late (28 weeks or beyond). Multivariate logistic regression included the covariates maternal CD4 count and infant HIV status (PCR). Results: Median CD4 counts for mother's of ART exposed and unexposed infants were 172 cells/mm3 (IQR116-229) and 191 cells/mm3 (136-220) respectively (p=0.11). Both groups were similar for risk of adverse infant outcomes. Prematurity rates were 6%(8/143) in ART-unexposed infants vs. 14%(129/949) in ART-exposed infants (p=0.01). Among late and early ART-exposed infants, 5%(24/461) and 22%(105/488) were premature respectively (p< 0.001). Among early ART-exposed infants, prematurity rates were 15%(22/147), 25%(54/220), and 24%(29/121) for Lop/rit-based, NVP-based and EFV-based regimens respectively (p=0.06). Among ART-unexposed infants 27%(60/225) were low birth weight (LBW) compared to 23%(120/524)of early ARTexposed and 18%(80/437) of late ART-exposed infants (p=0.037). Among early ART exposure, LBW rates were 18%, (27/153), 19%(44/229) and 35%(49/142) for Lop/Rit-based, NVP-based and EFV-based regimens respectively (p< 0.001). Conclusions: ART exposure to any regimen before 28 weeks of pregnancy was associated with prematurity but not low birth weight, among infants of women with advanced HIV disease. In the early treatment group, EFV-exposure was significantly associated with LBW compared to other regimens. These findings could help guide PMTCT policies in South Africa