Metabolomics in placental tissue from women living with HIV.

Abstract

INTRODUCTION\nIt is unknown whether antiretroviral drugs (ARVs) in women living with HIV (WLHIV) are associated with mitochondrial toxicity and altered fat oxidation and branched-chain amino acid metabolism in the placenta and fetus.\n\n\nMETHODS\nImmediately after delivery, we froze placental biopsies from 20 WLHIV and 20 matched uninfected women. We analyzed global biochemical profiles using high performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. We used t-tests, principle component analysis, hierarchical clustering, and random forest analysis (RFA) in our analysis.\n\n\nRESULTS\nTwelve WLHIV were on protease inhibitors, 6 on non-nucleoside reverse inhibitors, and 2 on integrase strand inhibitors with optimized backbone. Mean birthweight of HIV exposed neonates was significantly lower than unexposed neonates (3075g vs 3498g, p=0.01) at similar gestational age. RFA identified 30 of 702 analytes that differentiated the placental profiles of WLHIV from uninfected women with 72.5% predictive accuracy. Placental profiles of NNRTI-treated WLHIV exhibited lower levels of amino acids, including essential and branched-chain amino acids, and some medium chain acylcarnitines.\n\n\nDISCUSSION\nPlacental metabolism may be altered in WLHIV, possibly associated with ARVs exposure. The lower birth weight among neonates of WLHIV suggest the need for further studies considering potential deleterious effects of altered placenta metabolism on fetal growth and development.