As antiretroviral therapy (ART) becomes increasingly affordable and accessible to women of childbearing age across the globe, the number of children who are exposed to Human Immunodeficiency Viruses (HIV) but remain uninfected is on the rise, almost all of whom were also exposed to ART perinatally. Although ART has successfully aided in the decline of mother-to-child-transmission of HIV, the long-term effects of in utero exposure to ART on fetal and postnatal neurodevelopment remain unclear. Evaluating the safety and efficacy of therapeutic drugs for pregnant women is a challenge due to the historic limitations on their inclusion in clinical trials and the dynamic physiological states during pregnancy that can alter the pharmacokinetics of drug metabolism and fetal drug exposure. Thus, much of our data on the potential consequences of ART drugs on the developing nervous system comes from preclinical animal models and clinical observational studies. In this review, we will discuss the current state of knowledge and existing approaches to investigate whether ART affects fetal brain development, and describe novel human stem cell-based strategies that may provide additional information to better predict the impact of specific drugs on the human central nervous system.

随着抗逆转录病毒疗法 (ART) 越来越容易被全球育龄妇女负担得起，接触人类免疫缺陷病毒 (HIV) 但仍未感染的儿童人数正在增加，几乎所有这些儿童都曾接触过人类免疫缺陷病毒 (HIV)围产期 ART。尽管 ART 已成功帮助减少 HIV 母婴传播，但宫内 ART 暴露对胎儿和产后神经发育的长期影响仍不清楚。评估孕妇治疗药物的安全性和有效性是一项挑战，因为它们在临床试验中的历史限制以及妊娠期间的动态生理状态会改变药物代谢和胎儿药物暴露的药代动力学。因此，我们关于 ART 药物对发育中的神经系统的潜在后果的大部分数据来自临床前动物模型和临床观察研究。在这篇综述中，我们将讨论研究 ART 是否影响胎儿大脑发育的知识现状和现有方法，并描述新的基于人类干细胞的策略，这些策略可能提供更多信息以更好地预测特定药物对人类中枢神经系统的影响神经系统。