Background There are little data on changes in insulin sensitivity during the first few years of life following in utero human immunodeficiency virus (HIV) and antiretroviral (ARV) exposure. Methods The Tshilo Dikotla study enrolled pregnant persons with HIV (PWH) (receiving tenofovir/emtricitabine or lamivudine plus dolutegravir or efavirenz) and pregnant individuals without HIV, as well as their liveborn children. Newborns were randomized to receive either zidovudine (AZT) or nevirapine (NVP) postnatal prophylaxis. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was assessed at birth and 1, 18, 24, and 36 months of life. We fit linear mixed-effects models to evaluate the association between in utero HIV/ARV exposure and average HOMA-IR from birth through 36 months of life, adjusting for confounders. Results A total of 419 children were included (287 with in utero HIV/ARV exposure and uninfected [CHEU] and 132 without in utero HIV/ARV exposure [CHUU]). CHEU were born to older women (29.6 vs 25.3 years of age) with higher gravidity (3 vs 1). HOMA-IR was persistently higher in CHEU versus CHUU in adjusted analyses (mean difference of 0.07 in log10 HOMA-IR, P = .02) from birth through 36 months of life. Among CHEU, no differences in HOMA-IR were observed from birth through 36 months by in utero ARV exposure status or between AZT and NVP infant prophylaxis arms. Conclusions In utero HIV/ARV exposure was associated with lower insulin sensitivity throughout the first 36 months of life, indicating persistent early life metabolic disturbances which may raise concern for poorer metabolic health later in life.

中文翻译：

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博茨瓦纳子宫内 HIV 和抗逆转录病毒暴露后 36 个月内胰岛素敏感性降低：Tshilo Dikotla 研究结果

背景 关于子宫内人类免疫缺陷病毒 (HIV) 和抗逆转录病毒 (ARV) 暴露后生命最初几年胰岛素敏感性变化的数据很少。方法 Tshilo Dikotla 研究纳入了 HIV 感染孕妇 (PWH)（接受替诺福韦/恩曲他滨或拉米夫定加多替拉韦或依非韦伦治疗）和未感染 HIV 的孕妇及其活产子女。新生儿随机接受齐多夫定 (AZT) 或奈韦拉平 (NVP) 产后预防。胰岛素抵抗稳态模型评估 (HOMA-IR) 在出生时以及出生后 1、18、24 和 36 个月时进行评估。我们拟合线性混合效应模型来评估子宫内 HIV/ARV 暴露与从出生到生命 36 个月的平均 HOMA-IR 之间的关联，并调整混杂因素。结果 总共纳入 419 名儿童（287 名子宫内 HIV/ARV 暴露且未感染 [CHEU]，132 名未子宫内 HIV/ARV 暴露 [CHUU]）。 CHEU 是由高龄女性（29.6 岁 vs 25.3 岁）和较高妊娠率（3 vs 1）所生。在调整分析中，从出生到 36 个月，CHEU 的 HOMA-IR 持续高于 CHUU（log10 HOMA-IR 的平均差异为 0.07，P = .02）。在 CHEU 中，从出生到 36 个月，子宫内 ARV 暴露状态或 AZT 和 NVP 婴儿预防组之间没有观察到 HOMA-IR 存在差异。结论 子宫内 HIV/ARV 暴露与生命前 36 个月的胰岛素敏感性较低有关，表明生命早期持续存在代谢紊乱，这可能会引起人们对生命后期代谢健康状况较差的担忧。