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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.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.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/µL) 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 weighing75 kg; 1200 mg/day for patients weighing ≥75 kg) in combination with peginterferon alfa-2a (40KD) 180 µg 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]).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% CI, 0.68-1.93; P = .6119). In the 1000/1200 mg/day RBV dose group, the incidence of hemoglobin reductions100 g/L and anaemia reported as an adverse event were higher versus the standard 800 mg/day RBV dose group.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.

Purpose: The relationship between peginterferon/ribavirin exposure and the probability of achieving a sustained virologic response (SVR) in HIV-HCV coinfected patients is not well described. We conducted a retrospective analysis of HIV-HCV coinfected patients randomized to 48 weeks of treatment with peginterferon alfa-2a (40 kD) 180 µg/week and ribavirin 800 mg/day in the multinational APRICOT study to define optimal exposure thresholds. Method: Actual drug exposure was estimated in 287 patients, taking into consideration dose reductions for adverse events or laboratory abnormalities. Results: SVR overall and SVR in those completing treatment was, respectively, 29% and 37% among HCV genotype-1 patients and 59% and 68% among genotype non-1 patients. No patients with ≤40% exposure to ribavirin achieved an SVR. Receiver operating characteristic analysis identified that threshold exposures to both drugs of >75% (genotype-1) and >60% (genotype non-1) are associated with SVR. An existing generalized add...

In hepatitis C virus (HCV) monoinfection, the on-treatment virological response at Weeks 4 and 12 is a strong predictor of treatment outcomes.In a retrospective analysis, we examined these responses in 289 HIV-HCV coinfected patients treated with Peg-IFN alfa-2a /ribavirin for 48 weeks in a large randomized, multinational trial (APRICOT).Overall, 21% of patients achieved a rapid virological response at Week 4 and, of these, 88% achieved a sustained virological response. An early virological response at Week 12 was achieved in 71% of patients, and 56% of these patients achieved a sustained virological response. These results are similar to the sustained virological response rates obtained in monoinfected patients who achieve a rapid or early virological response. Patients who did not achieve a rapid virological response but who had unquantifiable HCV RNA or3 log10 drop over baseline also had high sustained virological response rates. A total of 46% of patients achieved undetectable HCV RNA (50 IU/mL) at Week 12. Multiple logistic regression analysis showed that infection with HCV genotype 2/3, low baseline HCV RNA level, and lower age predicted rapid virological response. Infection with HCV genotype 2/3 and low baseline HCV RNA level predicted early virological response.A rapid virological response is the best predictor of a sustained virological response, and lack of an early virological response is the best predictor of no sustained virological response. Such results are consistent with findings in HCV monoinfected patients.