Children who are HIV exposed-uninfected: does maternal ART regimen matter?

Abstract

Differences in health outcomes between children who are HIV-exposed but uninfected (CHEU) compared to children who are HIV-unexposed (CHU) have been reported both before and since the availability of antiretroviral therapy (ART) during pregnancy and breastfeeding. This review highlights recent studies investigating the impact of ART on the health, growth and development of CHEU. Several meta-analyses confirm higher rates of adverse birth outcomes among pregnant women with HIV compared to pregnant women without HIV. The highest risk of adverse birth outcomes is among women with HIV not receiving ART, and generally studies indicate that more time on ART is associated with lower risk of adverse birth outcomes; however, most data are from observational cohorts. Where studies have compared historic regimens, prior to dolutegravir use, adverse birth outcomes are more commonly associated with exposure to protease inhibitors. Recent population-based studies have not demonstrated an association between neural tube defects and dolutegravir exposure. In a recent, multisite randomized trial, infants born to mothers receiving dolutegravir vs. efavirenz had lower neonatal mortality, possibly mediated through reductions in small-for-gestational age and preterm birth. Neurodevelopment, neuroimaging and growth studies suggest a protective effect of earlier maternal ART initiation. Dolutegravir continues to appear safe in pregnancy. Randomized trials of specific regimens during pregnancy and breastfeeding, including long-acting and newer ART drugs with long-term follow-up of children, are critical to understand the contribution of ART exposure to CHEU outcomes.