Background:  Addition of boceprevir (BOC) to pegylated interferon (peg-IFN) and ribavirin (RBV) significantly increases sustained virological response among hepatitis C virus (HCV)-mono-infected patients for whom sustained virological response rates have been low. The objective of this phase 2 trial was to investigate the efficacy and safety of BOC+peg-IFN+RBV in HCV/HIV-co-infected patients.

Methods:  In this multi-center, double-blinded, international trial, patients with untreated HCV genotype 1 infections and HIV RNA <50 copies/mL were randomized in a 2:1 ratio to receive peg-IFN-2b 1.5 mg/kg/wk)+RBV (600 to 1400 mg/day, according to weight) + BOC 800 mg 3 times daily, or peg-IFN+RBV+placebo for 44 weeks. All had a 4-week lead-in of peg-IFN+RBV. ARV regimens that included NNRTI, zidovudine, or didanosine were not permitted. Patients were stratified by: cirrhosis/fibrosis (yes vs no) and baseline HCV RNA (<800,000 IU/mL vs ≥800,000 IU/mL). The primary efficacy endpoint was the achievement of sustained virologic response, undetectable plasma HCV RNA 24 weeks after the end of treatment. Secondary endpoints and planned interim analyses included proportion of subjects with undetectable HCV RNA at treatment week 4, 8, 12, 24, and treatment week 48 (end of treatment).

Results:  We randomized 100 patients between November 2009 and December 2010:  2 patients in the BOC arm did not receive medication; thus, 34 control and 64 experimental patients were treated. The majority were non-cirrhotic (95%), white (82%), male (69%) with a median age of ~43 years. Most had high baseline HCV RNA (88%) and HCV genotype 1a (65%). At treatment week 48, the rate of undetectable HCV RNA was 63.9% and 29.4% in the BOC and control arm, respectively (see the table). In all, 61% of the BOC group and 32% of the control group completed 48 weeks of treatment. Discontinuation due to adverse events occurred in 20% and 9% in the BOC and control groups, respectively. There were 9% and 53% HCV treatment failures in the BOC and control groups respectively. Compared to the control group, BOC patients were more likely to have decreased appetite, pyrexia, dysgeusia, vomiting, asthenia, anemia, and neutropenia. By week 48, 2 and 3 patients in the BOC and control groups, respectively, had HIV RNA virologic failure.

Conclusions:  The addition of BOC to peg-IFN+RBV was associated with higher rates of undetectable HCV RNA at all time points, including the end of treatment. The safety and tolerability profile was consistent with that observed in HCV-mono-infected patients.