It is unknown whether antiretroviral (ARV) drugs 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. Immediately 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. Twelve WLHIV were on protease inhibitors, six on non-nucleoside reverse inhibitors, and two on integrase strand inhibitors with optimized backbone. Mean birth weight of HIV-exposed neonates was significantly lower than unexposed neonates (3,075 g vs. 3,498 g, p = .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 non-nucleoside reverse transcriptase inhibitor (NNRTI)-treated WLHIV exhibited lower levels of amino acids, including essential and branched-chain amino acids, and some medium-chain acylcarnitines. Placental metabolism may be altered in WLHIV, possibly associated with ARV exposure. The lower birth weight among neonates of WLHIV suggests the need for further studies considering potential deleterious effects of altered placenta metabolism on fetal growth and development.

中文翻译：

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感染 HIV 的女性胎盘组织中的代谢组学

目前尚不清楚感染 HIV 的女性 (WLHIV) 的抗逆转录病毒 (ARV) 药物是否与胎盘和胎儿的线粒体毒性以及脂肪氧化和支链氨基酸代谢的改变有关。分娩后，我们立即冻结了 20 名 WLHIV 和 20 名匹配的未感染妇女的胎盘活检。我们使用高效液相色谱/串联质谱和气相色谱/质谱分析了全球生化概况。我们用过-我们分析中的测试、主成分分析、层次聚类和随机森林分析 (RFA)。十二个 WLHIV 使用蛋白酶抑制剂，六个使用非核苷反向抑制剂，两个使用具有优化骨架的整合酶链抑制剂。暴露于 HIV 的新生儿的平均出生体重明显低于未暴露的新生儿（3,075 克对 3,498 克，p = .01) 在相似的胎龄。RFA 确定了 702 种分析物中的 30 种，这些分析物将 WLHIV 的胎盘特征与未感染的女性区分开来，预测准确度为 72.5%。非核苷逆转录酶抑制剂 (NNRTI) 处理的 WLHIV 的胎盘概况显示出较低水平的氨基酸，包括必需氨基酸和支链氨基酸，以及一些中链酰基肉碱。WLHIV 的胎盘代谢可能发生改变，可能与 ARV 暴露有关。WLHIV 新生儿出生体重较低表明需要进一步研究，以考虑胎盘代谢改变对胎儿生长发育的潜在有害影响。