Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia, Avda Blasco Ibáñez n.15-17, 46010 Valencia, Spain.
Trends Pharmacol Sci. 2011 Dec;32(12):715-25. doi: 10.1016/j.tips.2011.07.007. Epub 2011 Sep 6.
The combined pharmacological approach to the treatment of HIV infection, known as highly active antiretroviral therapy (HAART), has dramatically reduced AIDS-related morbidity and mortality. However, its use has been associated with serious adverse reactions, of which those resulting from mitochondrial dysfunction are particularly widespread. Nucleos(t)ide-reverse transcriptase inhibitors (NRTIs) have long been considered the main source of HAART-related mitochondrial toxicity due to their ability to inhibit Pol-γ, the DNA polymerase responsible for the synthesis of mitochondrial DNA. Nevertheless, accumulating evidence points to a more complex relationship between these organelles and NRTIs. Also, alternative pathways by which other groups of anti-HIV drugs (non-nucleoside reverse transcriptase inhibitors and protease inhibitors) interfere with mitochondria have been suggested, although their implications, both pharmacological and clinical, are open to debate. This review aims to provide a comprehensive overview of the mechanisms and factors which influence the mitochondrial involvement in the toxicity of all three major classes of anti-HIV drugs.
联合应用药理学方法治疗 HIV 感染，即高效抗逆转录病毒疗法（HAART），显著降低了 AIDS 相关发病率和死亡率。然而，其使用与严重不良反应相关，其中由线粒体功能障碍引起的不良反应尤其广泛。核苷酸逆转录酶抑制剂（NRTIs）由于能够抑制负责合成线粒体 DNA 的 DNA 聚合酶 Pol-γ，长期以来被认为是 HAART 相关线粒体毒性的主要来源。然而，越来越多的证据表明，这些细胞器与 NRTIs 之间存在更复杂的关系。此外，还提出了其他组抗 HIV 药物（非核苷类逆转录酶抑制剂和蛋白酶抑制剂）干扰线粒体的替代途径，尽管它们的药理学和临床意义仍存在争议。本综述旨在全面概述影响三种主要抗 HIV 药物的线粒体毒性的机制和因素。
