Distinct biochemical phenotypes of HIV exposed infants driven by antiviral medication

Pregnant women with HIV control viral replication with antiretrovirals and give birth to HIV-exposed uninfected infants (HEU). The children, however, exhibit increased morbidity and mortality due to severe infections, as well as cognitive and growth abnormalities. In this study, we performed high-resolution, untargeted metabolomics on 123 HIV-exposed mother-baby pairs and 117 control pairs without HIV. High concentrations of the antiretroviral efavirenz and its metabolites were detected in maternal blood and cord blood. The metabolomic differences between HEU participants and controls reflect perturbed pathways of steroids, tryptophan and bile acids, and they largely consisted of metabolites that were correlated with efavirenz concentrations within the HEU group. The results suggest a major contribution of the drug to the abnormal biochemical profile of HEU infants born to mothers treated with efavirenz.