Peginterferon alfa-2a plus ribavirin for HIV-HCV genotype 1 coinfected patients: a randomized international trial.

Background: The safety and efficacy of weight-based ribavirin (RBV) dosing regimens in patients with HIV-HCV coinfection has not been demonstrated in randomized clinical trials. Objective: This randomized, double-blind, international, parallel-group study in specialist outpatient clinics in the United States, Spain, and Portugal compares the efficacy and safety of 2 RBV dose regimens (800 mg/day and 1000/1200 mg/day) combined with peginterferon alfa-2a (40KD) in patients with HIV-HCV (genotype 1) coinfection. Methods: Patients with HIV-HCV coinfection, quantifiable HCV RNA in serum, HCV genotype-1 infection, compensated liver disease, and stable HIV disease (CD4+ count >= 100 cells/mu L) with or without ongoing antiretroviral therapy were randomized to 48 weeks' treatment with RBV at standard dose (800 mg/day) or weight-based dose (1000 mg/day for patients weighing <75 kg; 1200 mg/day for patients weighing >= 75 kg) in combination with peginterferon alfa-2a (40KD) 180 mu g once a week. Planned enrollment was 400 patients with >= 100 non-Latino African Americans. The primary endpoint was sustained virological response (SVR) (undetectable HCV RNA [<20 IU/mL] at the end of a 24-week untreated follow-up period [week 72]). Results: SVR rates were 19% (26/135) and 22% (60/275) in patients randomized to RBV 800 mg/day and 1000/1200 mg/day, respectively (odds ratio, 1.15; 95% Cl, 0.68-1.93; P = .6119). In the 1000/1200 mg/day RBV dose group, the incidence of hemoglobin reductions <100 g/L and anaemia reported as an adverse event were higher versus the standard 800 mg/day RBV dose group. Conclusions: Compared with the standard RBV dose (800 mg/day), weight-based RBV dosing (1000/1200 mg/day) did not significantly increase SVR rates, but did increase the incidence of anemia in HIV-HCV (genotype 1) coinfected patients.