Foster Emma G, Gendelman Howard E, Bade Aditya N
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Pharmaceuticals (Basel). 2022 Dec 9;15(12):1533. doi: 10.3390/ph15121533.
Children born to mothers, with or at risk, of human immunodeficiency virus type-1 (HIV-1) infection are on the rise due to affordable access of antiretroviral therapy (ART) to pregnant women or those of childbearing age. Each year, up to 1.3 million HIV-1-infected women on ART have given birth with recorded mother-to-child HIV-1 transmission rates of less than 1%. Despite this benefit, the outcomes of children exposed to antiretroviral drugs during pregnancy, especially pre- and post- natal neurodevelopment remain incompletely understood. This is due, in part, to the fact that pregnant women are underrepresented in clinical trials. This is underscored by any potential risks of neural tube defects (NTDs) linked, in measure, to periconceptional usage of dolutegravir (DTG). A potential association between DTG and NTDs was first described in Botswana in 2018. Incidence studies of neurodevelopmental outcomes associated with DTG, and other integrase strand transfer inhibitors (INSTIs) are limited as widespread use of INSTIs has begun only recently in pregnant women. Therefore, any associations between INSTI use during pregnancy, and neurodevelopmental abnormalities remain to be explored. Herein, United States Food and Drug Administration approved ARVs and their use during pregnancy are discussed. We provide updates on INSTI pharmacokinetics and adverse events during pregnancy together with underlying mechanisms which could affect fetal neurodevelopment. Overall, this review seeks to educate both clinical and basic scientists on potential consequences of INSTIs on fetal outcomes as a foundation for future scientific investigations.
由于孕妇或育龄妇女能够负担得起抗逆转录病毒疗法（ART），感染1型人类免疫缺陷病毒（HIV-1）的母亲所生子女的数量正在增加。每年，多达130万接受抗逆转录病毒治疗的HIV-1感染女性分娩，母婴HIV-1传播率记录低于1%。尽管有这一益处，但孕期接触抗逆转录病毒药物的儿童的结局，尤其是产前和产后神经发育情况仍未完全了解。部分原因是孕妇在临床试验中的代表性不足。神经管缺陷（NTDs）的任何潜在风险在一定程度上与多替拉韦（DTG）的受孕前后使用有关，这一点凸显了上述情况。DTG与NTDs之间的潜在关联最早于2018年在博茨瓦纳被描述。由于整合酶链转移抑制剂（INSTIs）在孕妇中的广泛使用最近才开始，与DTG及其他整合酶链转移抑制剂相关的神经发育结局的发病率研究有限。因此，孕期使用整合酶链转移抑制剂与神经发育异常之间的任何关联仍有待探索。本文讨论了美国食品药品监督管理局批准的抗逆转录病毒药物及其在孕期的使用。我们提供了整合酶链转移抑制剂在孕期的药代动力学和不良事件的最新情况，以及可能影响胎儿神经发育的潜在机制。总体而言，本综述旨在让临床科学家和基础科学家了解整合酶链转移抑制剂对胎儿结局的潜在影响，为未来的科学研究奠定基础。
