• Taha Taha
• NICHD R21 9/30/15-8/31/17

Globally, there is a renewed commitment to eliminate mother-to-child transmission (MTCT) of HIV. In Malawi, universal, lifelong combination antiretroviral treatment (ART) is recommended for all HIV-infected women who are pregnant, breastfeeding, or between pregnancies. In this approach, known as Option B+, combination ART is prescribed irrespective of a woman’s immune status or stage of HIV clinical disease. Findings from a recent, large multisite randomized clinical trial known as PROMISE showed that combination ART can reduce rates of MTCT of HIV to very low levels (~0.5%). The efficacy results of the PROMISE trial support the 2013 WHO guidelines where use of combination ART was recommended. The PROMISE study also showed that some ART drugs may be associated with adverse pregnancy outcomes such as low birth weight (LBW) and preterm (PT) birth and may increase early neonatal death. While PROMISE did not randomize women to Malawi’s specific Option B+ regimen, some drugs are common to both regimens. We propose an observational study with two specific aims that relate to safety findings from PROMISE. In Aim 1, we will compare pregnancy outcomes (LBW, PT and intrauterine growth restriction) between HIV-infected and HIV-uninfected women. Aim 2 will compare survival between HIV-exposed infants (born to HIV-infected mothers) and HIV-unexposed infants (born to HIV-uninfected mothers). Earlier studies that predated ART use in Africa showed substantial differences in pregnancy outcomes and infant survival among HIV-infected untreated women and their children compared to HIV-uninfected women and their children. These differences were attributed to HIV. The goal of the proposed study is to assess if universal ART, as in Option B+, has eliminated these differences. This is an urgent and important question. If substantial differences in pregnancy outcomes and survival associated with HIV still remain, other factors underlying these outcomes will need further examination. The proposed study is exploratory and will provide preliminary data to conceptualize larger studies to examine the complex causes of these outcomes – including safety of ARTs – and to determine if further interventions are needed. The study will be conducted in Blantyre, Malawi in the main hospital and several health centers. A total sample of 1350 women will be enrolled; 675 HIV-infected healthy women on Option B+ ART prior to or during pregnancy and 675 HIV-uninfected women. These women and their children will be prospectively followed postnatally for up to one year. Birth weight and gestational age will be assessed at birth and case reports forms will be completed at enrollment and each follow-up visit.  (From NIH Report)