Funk Michele Jonsson, Belinson Suzanne E, Pimenta Jeanne M, Morsheimer Megan, Gibbons David C
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599-7521, USA.
Drug Saf. 2007;30(10):845-59. doi: 10.2165/00002018-200730100-00004.
Although antiretroviral therapy (ART) is critical for preventing mother-to-child transmission of HIV, concern has been raised about the possibility that it may cause mitochondrial dysfunction in infants. There is adequate evidence for a mechanism by which exposure to nucleoside reverse transcriptase inhibitors (NRTIs) could lead to mitochondrial dysfunction; animal studies have shown evidence of mitochondrial dysfunction in the offspring of animals treated with NRTIs and mitochondrial disorders occur in adults treated with NRTIs. This systematic review synthesises the published research on mitochondrial dysfunction and disorders in infants exposed to HIV and antiretrovirals. We found conflicting evidence regarding the possible association of in utero ART exposure with mortality and morbidity due to mitochondrial dysfunction. ART exposure in utero or postpartum was associated with persistent decreases in lymphocytes, neutrophils and platelets as well as an increased risk of transient lactic acidaemia, anaemia and mitochondrial DNA depletion, although these laboratory findings were generally not associated with clinical symptoms. We conclude that large, prospective studies of HIV-exposed infants are needed to resolve the discrepant results regarding morbidity and mortality related to mitochondrial disorders, to ascertain the clinical significance of effects on laboratory values, to determine whether or not the incidence of mitochondrial disorders differs by regimen and to develop predictive models that might identify which infants are at the greatest risk. The challenges that remain to be addressed include the development of a sensitive but affordable screening algorithm in combination with specific diagnostic criteria; consistent collection of data on ART exposure and other risk factors, long-term follow-up of HIV-exposed but uninfected children and implementation in resource-limited settings.
尽管抗逆转录病毒疗法（ART）对于预防母婴传播HIV至关重要，但人们对其可能导致婴儿线粒体功能障碍的可能性表示担忧。有充分证据表明，接触核苷类逆转录酶抑制剂（NRTIs）可能导致线粒体功能障碍的机制；动物研究已显示接受NRTIs治疗的动物后代出现线粒体功能障碍的证据，且接受NRTIs治疗的成人会发生线粒体疾病。本系统评价综合了已发表的关于暴露于HIV和抗逆转录病毒药物的婴儿线粒体功能障碍和疾病的研究。我们发现，关于宫内ART暴露与线粒体功能障碍导致的死亡率和发病率之间可能存在的关联，证据相互矛盾。宫内或产后ART暴露与淋巴细胞、中性粒细胞和血小板持续减少以及短暂性乳酸性血症、贫血和线粒体DNA耗竭风险增加有关，尽管这些实验室检查结果通常与临床症状无关。我们得出结论，需要对暴露于HIV的婴儿进行大规模前瞻性研究，以解决与线粒体疾病相关的发病率和死亡率方面的差异结果，确定对实验室值影响的临床意义，确定线粒体疾病的发病率是否因治疗方案而异，并开发可能识别哪些婴儿风险最大的预测模型。仍有待解决的挑战包括开发一种敏感但经济实惠的筛查算法并结合特定诊断标准；一致收集关于ART暴露和其他风险因素的数据，对暴露于HIV但未感染的儿童进行长期随访，并在资源有限的环境中实施。
