Coelho Antonio Victor Campos, Tricarico Paola Maura, Celsi Fulvio, Crovella Sergio
Department of Genetics, Federal University of Pernambuco, Avenida da Engenharia, Cidade Universitária, 50740-600 Recife, Brazil.
Institute for Maternal and Child Health, Scientific Institute for Research, Hospitalization and Care (IRCCS) Burlo Garofolo, 34137 Trieste, Italy.
Int J Mol Sci. 2017 Feb 15;18(2):423. doi: 10.3390/ijms18020423.
Since the worldwide introduction of antiretroviral therapy (ART) in human immunodeficiency virus type 1, HIV-1-positive mothers, together with HIV-1 testing prior to pregnancy, caesarian birth and breastfeeding cessation with replacement feeding, a reduction of HIV-1 mother-to-child transmission (MTCT) has been observed in the last few years. As such, an increasing number of children are being exposed in utero to ART. Several questions have arisen concerning the neurological effects of ART exposure in utero, considering the potential effect of antiretroviral drugs on the central nervous system, a structure which is in continuous development in the fetus and characterized by great plasticity. This review aims at discussing the possible neurological impairment of children exposed to ART in utero, focusing attention on the drugs commonly used for HIV-1 MTCT prevention, clinical reports of ART neurotoxicity in children born to HIV-1-positive mothers, and neurologic effects of protease inhibitors (PIs), especially ritonavir-"boosted" lopinavir (LPV/r) in cell and animal central nervous system models evaluating the potential neurotoxic effect of ART. Finally, we present the findings of a meta-analysis to assess the effects on the neurodevelopment of children exposed to ART in utero.
自从抗逆转录病毒疗法（ART）在全球范围内应用于人类免疫缺陷病毒1型（HIV-1）感染以来，HIV-1阳性母亲在孕期进行HIV-1检测、选择剖宫产以及停止母乳喂养并采用替代喂养方式，使得过去几年中HIV-1母婴传播（MTCT）有所减少。因此，越来越多的儿童在子宫内就接触到了ART。考虑到抗逆转录病毒药物对中枢神经系统的潜在影响，而中枢神经系统在胎儿期处于持续发育状态且具有很大的可塑性，关于子宫内接触ART对神经方面的影响就出现了几个问题。本综述旨在讨论子宫内接触ART的儿童可能出现的神经功能损害，重点关注常用于预防HIV-1母婴传播的药物、HIV-1阳性母亲所生儿童中ART神经毒性的临床报告，以及在细胞和动物中枢神经系统模型中评估ART潜在神经毒性作用时蛋白酶抑制剂（PIs）尤其是利托那韦增效洛匹那韦（LPV/r）的神经学效应。最后，我们展示一项荟萃分析的结果，以评估子宫内接触ART对儿童神经发育的影响。
