Combination therapy with telaprevir for chronic hepatitis C virus genotype 1 infection in patients with HIV a randomized trial

Background: Telaprevir (TVR) plus peginterferon-o2a (PEG-IFN- o2a) and ribavirin substantially increases treatment efficacy for genotype 1 chronic hepatitis C virus (HCV) infection versus PEG-IFN- a2a-ribavirin alone. Its safety and efficacy in patients with HCV and HIV-1 are unknown. Objective: To assess the safety and efficacy of TVR plus PEG-IFN- a2a-ribavirin in patients with genotype 1 HCV and HIV-1 and to evaluate pharmacokinetics of TVR and antiretrovirals during coadministration. Design: Phase 2a, randomized, double-blind, placebo-controlled study. (ClinicalTrials.gov: NCT00983853) Setting: 16 international multicenter sites. Patients: 62 patients with HCV genotype 1 and HIV-1 who were HCV treatment-naive and receiving 0 or 1 of 2 antiretroviral regimens were randomly assigned to TVR plus PEG-IFN-a2a-ribavirin or placebo plus PEG-IFN-a2a-ribavirin for 12 weeks, plus 36 weeks of PEG-IFN-a2a-ribavirin. Measurements: HCV RNA concentrations. Results: Pruritus, headache, nausea, rash, and dizziness were higher with TVR plus PEG-IFN-a2a-ribavirin during the first 12 weeks. During this period, serious adverse events occurred in 5% (2 in 38) of those receiving TVR plus PEG-IFN-a2a-ribavirin and 0% (0 in 22) of those receiving placebo plus PEG-IFN-α2a-ribavirin; the same number in both groups discontinued treatment due to adverse events. Sustained virologic response occurred in 74% (28 in 38) of patients receiving TVR plus PEG-IFN-α2a-ribavirin and 45% (10 in 22) of patients receiving placebo plus PEG-IFN-α2a-ribavirin. Rapid HCV suppression was seen with TVR plus PEG-IFN-α2a- ribavirin (68% [26 in 38 patients] vs. 0% [0 in 22 patients] undetectable HCV RNA levels by week 4). Two patients had ontreatment HCV breakthrough with TVR-resistant variants. Patients treated with antiretroviral drugs had no HIV breakthroughs; antiretroviral exposure was not substantially modified by TVR. Limitation: Small sample size and appreciable dropout rate. Conclusion: In patients with HCV and HIV-1, more adverse events occurred with TVR versus placebo plus PEG-IFN-α2a-ribavirin; these were similar in nature and severity to those in patients with HCV treated with TVR. With or without concomitant antiretrovirals, sustained virologic response rates were higher in patients treated with TVR versus placebo plus PEG-IFN-α2a-ribavirin.