Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Heidelberg, Germany.
Int Rev Cell Mol Biol. 2010;280:219-79. doi: 10.1016/S1937-6448(10)80005-X. Epub 2010 Mar 18.
Even though potent antiretrovirals are available against human immunodeficiency virus (HIV)-1 infection, therapy fails in a significant fraction of patients. Among the most relevant reasons for treatment failure are drug toxicity and side effects, but also the development of viral resistance towards the drugs applied. Efflux by ATP-binding cassette (ABC-) transporters represents one major mechanism influencing the pharmacokinetics of antiretroviral drugs and particularly their distribution, thus modifiying the concentration within the infected cells, that is, at the site of action. Moreover, drug-drug interactions may occur at the level of these transporters and modulate their activity or expression thus influencing the efficacy and toxicity of the substrate drugs. This review summarizes current knowledge on the interaction of antiretrovirals used for HIV-1 therapy with ABC-transporters and highlights the impact of ABC-transporters for cellular resistance and therapeutic success. Moreover, the suitability of different cell models for studying the interaction of antiretrovirals with ABC-transporters is discussed.
尽管针对人类免疫缺陷病毒 (HIV)-1 感染有强效的抗逆转录病毒药物，但治疗在很大一部分患者中失败。治疗失败的最相关原因之一是药物毒性和副作用，但也包括病毒对所应用药物的耐药性的发展。ATP 结合盒 (ABC-) 转运蛋白的外排代表了影响抗逆转录病毒药物药代动力学的一个主要机制，特别是它们的分布，从而改变了感染细胞内的浓度，也就是作用部位的浓度。此外，药物-药物相互作用可能发生在这些转运体水平，并调节它们的活性或表达，从而影响底物药物的疗效和毒性。这篇综述总结了目前关于用于 HIV-1 治疗的抗逆转录病毒药物与 ABC 转运体相互作用的知识，并强调了 ABC 转运体对细胞耐药性和治疗成功的影响。此外，还讨论了不同细胞模型在研究抗逆转录病毒药物与 ABC 转运体相互作用中的适用性。
