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Hepatitis C virus (HCV) co-infection is common among HIV-infected patients. Over the past 15 years, effective HIV treatment has led to dramatic reductions in the incidence of AIDS-related death; over the same time period, HCV-related liver disease has emerged as a major cause of morbidity and mortality. Treatment with peginterferon (PEG-IFN) and ribavirin (RBV) has been recommended for the treatment of HCV infection in HIV-infected patients at the greatest risk of developing liver disease. However, the effectiveness of this HCV treatment has been low because of limited efficacy in patients infected with HCV genotype 1. More recently, HCV NS3/4A protease inhibitors, telaprevir and boceprevir, in combination with PEG-IFN/RBV have led to significantly higher sustained viral response rates in HIV-uninfected patients with HCV genotype 1 infection. The potential use of these agents in patients with HIV/HCV co-infection is complicated by the potential for drug interactions between antiretroviral drugs and the HCV protease inhibitors and uncertainty regarding the safety and effectiveness of the combination therapy in this population.