Boceprevir Drug Combination for Hepatitis C Treatment in People With and Without HIV

Chronic hepatitis C virus (HCV) infection is a major public health problem with an estimated 180 million people infected worldwide. In the United States, an estimated 4.1 million people are infected and HCV is the principal cause of death from liver disease and leading indication for liver transplantation. A combination of ribavirin (RBV) and pegylated interferon (peg-IFN) is the currently recommended therapy for chronic HCV infection. However, this therapy achieves viral clearance in only 19% to 52% of patients infected with HCV genotype 1 and 76% to 80% of patients infected with genotypes 2 and 3. Current therapy is also associated with a high incidence of adverse events and low cure rates in several populations. Novel therapies that do not rely on an interferon backbone will be required to enhance cure rates in various populations. Recent data show that adding an HCV serine protease inhibitor (such as boceprevir \[BOC\]) to peg-IFN and RBV results in HCV eradication rates of 70% to 80% among HCV-monoinfected subjects. However, whether human immunodeficiency virus (HIV)-infected subjects will have similar rates of response to triple combination therapy is presently not known. Previous data have suggested that HIV-infected patients with chronic HCV infection have much lower eradication rates to peg-IFN and RBV than HCV-monoinfected subjects. This study will explore whether HIV/HCV-coinfected subjects have a lower response rate to a BOC/peg-IFN/RBV regimen than HCV-monoinfected subjects. Participants who have chronic hepatitis C genotype 1 monoinfection (N=50) or coinfection with HIV-1 (N=50), and who are na(SqrRoot) ve to IFN-based HCV treatment, will receive combination therapy with BOC (800 mg three times a day, every 7 to 9 hours, with food), weekly peg-IFN alpha-2b (1.5 mcg/kg/week) and twice daily RBV (weight based) for a maximum of 44 weeks, after a 4-week lead-in of peg-IFN and RBV. BOC received recent FDA approval for treating HCV monoinfection in combination with peg-IFN and RBV, and the approved labeling will be followed in this study. The primary endpoint is comparative efficacy in HCV-monoinfected and HIV/HCV-coinfected subjects. Secondary endpoints include determination of host predictors for therapeutic response, emergence of resistance biomarkers, and early viral kinetics. The findings from this study will aid in the understanding of whether HIV infection affects HCV antiviral and host responses to combination therapy using BOC/peg-IFN alfa-2b/RBV.