Department of Biomedical and Clinical Sciences L. Sacco, III Division of Infectious Diseases, University of Milan, Via GB Grassi 74, 20157 Milan, Italy.
Unit of Clinical Pharmacology, Luigi Sacco University Hospital, Via GB Grassi 74, 20157 Milan, Italy.
Int J Antimicrob Agents. 2015 May;45(5):545-9. doi: 10.1016/j.ijantimicag.2014.12.035. Epub 2015 Feb 21.
Complex drug-drug interactions have been reported with concurrent administration of telaprevir (TVR) and human immunodeficiency virus (HIV) protease inhibitors (PIs), leading to relevant limitations of the therapeutic options for patients coinfected with hepatitis C virus (HCV) and HIV. However, little is known about the pharmacokinetics and drug interactions between TVR and antiretrovirals in HIV/HCV-coinfected patients with advanced liver fibrosis. Here we report the pharmacokinetics of TVR and antiretrovirals in a cohort of HIV/HCV genotype 1-coinfected patients with advanced liver fibrosis treated with TVR-based triple anti-HCV therapy. No significant differences were observed in the pharmacokinetics of atazanavir, amprenavir or tenofovir at baseline and at Day 15 of TVR, whereas the AUC0-4h of darunavir was 36% lower in the presence of TVR (AUC0-4h 15007ngh/mL and 9563ngh/mL at baseline and at Day 15 of TVR administration, respectively). Noteworthy, the AUC0-4h, Cmin and Cmax of raltegravir were reduced by 61%, 50% and 64%, respectively. However, none of the patient's plasma levels of tenofovir, atazanavir, amprenavir or raltegravir declined below their minimum effective concentrations even in association with TVR, and no HIV treatment failure occurred. A non-significant trend for lower TVR exposure was seen in patients concomitantly given amprenavir versus those given atazanavir (AUC0-4h, 9840ngh/mL and 13345ngh/mL, respectively). In conclusion, this study highlighted the feasibility of maintaining the current antiretroviral regimen in HIV/HCV-coinfected patients, even when significant interactions with TVR are predictable, whenever a change of HIV PIs is not deemed appropriate.
已有报道称，替拉瑞韦（TVR）与人类免疫缺陷病毒（HIV）蛋白酶抑制剂（PI）同时使用时会发生复杂的药物相互作用，从而导致同时感染丙型肝炎病毒（HCV）和 HIV 的患者的治疗选择受到限制。然而，对于合并有晚期肝纤维化的 HIV/HCV 合并感染患者，TVR 与抗逆转录病毒药物之间的药代动力学和药物相互作用知之甚少。在此，我们报告了一组接受 TVR 为基础的三联抗 HCV 治疗的合并有晚期肝纤维化的 HIV/HCV 基因型 1 合并感染患者中 TVR 和抗逆转录病毒药物的药代动力学。在 TVR 治疗第 15 天，未观察到阿扎那韦、安普那韦或替诺福韦的药代动力学有显著差异，而在 TVR 存在的情况下，达芦那韦的 AUC0-4h 降低了 36%（AUC0-4h 在基线时分别为 15007ngh/mL 和 9563ngh/mL，在 TVR 给药第 15 天）。值得注意的是，阿扎那韦的 AUC0-4h、Cmin 和 Cmax 分别降低了 61%、50%和 64%。然而，即使与 TVR 联合使用，替诺福韦、阿扎那韦、安普那韦或拉替拉韦的患者血浆水平均未降至最低有效浓度以下，也未发生 HIV 治疗失败。与阿扎那韦相比，同时给予安普那韦的患者 TVR 暴露量呈显著下降趋势（AUC0-4h 分别为 9840ngh/mL 和 13345ngh/mL）。结论：该研究强调了在可预测到与 TVR 发生显著相互作用的情况下，即使需要更换 HIV PIs 也不合适时，在合并有 HIV/HCV 感染的患者中维持现有抗逆转录病毒方案的可行性。
