Venhoff Nils, Walker Ulrich A
Department of Rheumatology and Clinical Immunology, Medizinische Universitätsklinik, Hugstetterstr. 55, D-79106 Freiburg, Germany.
Expert Opin Drug Saf. 2006 May;5(3):373-81. doi: 10.1517/14740338.5.3.373.
Nucleoside analogue reverse transcriptase inhibitors (NRTIs) have substantially lowered the risk of the mother-to-child transmission of HIV. Evidence of mitochondrial toxicity in vitro, in animal models and in adult HIV-infected patients, has raised concern about the perinatal safety of these antiretrovirals. In zidovudine-exposed, but HIV-uninfected infants, transient anaemia and additional long-term blood abnormalities (neutropenia, thrombopenia and lymphopenia) and hyperlactatemia have been documented. The overall risk of mortality and congenital abnormalities does not appear to be increased, but rare mitochondrial events cannot be excluded for lack of statistical power. French data suggest an above background incidence of mitochondrial symptomatology. Preclinical data demonstrate zidovudine also to be a carcinogen. Long-term systematic follow-up of exposed babies in large cohorts is needed, as are randomised trials with NRTIs carrying a lower risk of mitochondrial toxicity.
核苷类逆转录酶抑制剂（NRTIs）已大幅降低了HIV母婴传播的风险。体外、动物模型及成年HIV感染患者中线粒体毒性的证据，引发了对这些抗逆转录病毒药物围产期安全性的担忧。在暴露于齐多夫定但未感染HIV的婴儿中，已记录到短暂性贫血以及其他长期血液异常（中性粒细胞减少、血小板减少和淋巴细胞减少）和高乳酸血症。总体死亡率和先天性异常的风险似乎并未增加，但由于缺乏统计学效力，不能排除罕见的线粒体事件。法国的数据表明线粒体症状的发生率高于背景水平。临床前数据表明齐多夫定也是一种致癌物。需要对大量队列中暴露婴儿进行长期系统随访，以及开展线粒体毒性风险较低的NRTIs随机试验。
