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.

The authors have declared no competing interest.

This work was in part supported by NIH grants R01 HD107793 (AW), R01 AI149746 (SL) and ARPA-H award D24AC00345. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders.

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The study was approved by the Ethics Committee of the Witwatersrand University and by the Colorado Multiple Institutions Review Board.

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