Esposito Isabella, Labarga Pablo, Barreiro Pablo, Fernandez-Montero José V, de Mendoza Carmen, Benítez-Gutiérrez Laura, Peña José M, Soriano Vicente
a 1 La Paz University Hospital, Infectious Diseases Unit , Madrid, Spain +34 91 7277000 ;
Expert Opin Drug Saf. 2015;14(9):1421-34. doi: 10.1517/14740338.2015.1073258. Epub 2015 Jul 28.
Roughly 20% of HIV-positive persons worldwide are coinfected with hepatitis C virus (HCV). The recent advent of direct-acting antivirals (DAA) that cure most hepatitis C patients has attracted much attention. Knowledge on drug interactions between DAA and antiretrovirals (ARV) may allow maximizing antiviral efficacy while minimizing drug-related toxicities.
We review the most frequent side effects and clinically significant drug interactions between DAA and ARV. We further discuss how they can be prevented and managed in HIV/HCV-coinfected patients.
The safety profile of current DAA and the most recently approved ARV is quite favorable. Interactions between DAA and ARV could be frequent in clinical practice. The most common drug interactions affect drug metabolism by inducing or inhibiting the cytochrome P450 system, leading to abnormal drug exposures. Throughout this mechanism HCV and HIV protease inhibitors interact, especially when co-formulated with ritonavir as a pharmacoenhancer, and non-nucleoside HCV and HIV polymerase inhibitors. In contrast, HIV and HCV nucleos(t)ide polymerase inhibitors, and most HCV NS5A inhibitors (i.e., ledipasvir) and HIV integrase inhibitors (i.e., dolutegravir), do not or only marginally affect CYP450, and therefore are free of significant drug interactions. Exposure to HIV and HCV nucleos(t)ide analogues (i.e., tenofovir and sofosbuvir, respectively) is subject to induction/inhibition of drug transporters (i.e., P-glycoprotein).
全球约20%的HIV阳性者合并感染丙型肝炎病毒（HCV）。近期出现的能治愈大多数丙型肝炎患者的直接抗病毒药物（DAA）备受关注。了解DAA与抗逆转录病毒药物（ARV）之间的药物相互作用，有助于在将药物相关毒性降至最低的同时，使抗病毒疗效最大化。
我们综述了DAA与ARV之间最常见的副作用及具有临床意义的药物相互作用。我们还进一步讨论了在HIV/HCV合并感染患者中如何预防和处理这些情况。
当前DAA和最新获批的ARV的安全性相当良好。在临床实践中，DAA与ARV之间的相互作用可能较为常见。最常见的药物相互作用通过诱导或抑制细胞色素P450系统影响药物代谢，导致药物暴露异常。在整个机制中，HCV和HIV蛋白酶抑制剂相互作用，尤其是与利托那韦作为药物增强剂共同配制时，以及非核苷类HCV和HIV聚合酶抑制剂。相比之下，HIV和HCV核苷（酸）聚合酶抑制剂，以及大多数HCV NS5A抑制剂（如雷迪帕韦）和HIV整合酶抑制剂（如多替拉韦），对CYP450没有或仅有轻微影响，因此不存在显著的药物相互作用。HIV和HCV核苷（酸）类似物（分别为替诺福韦和索磷布韦）的暴露受到药物转运体（如P-糖蛋白）的诱导/抑制作用影响。
