Focus on drug interactions: the challenge of treating hepatitis C virus infection with direct-acting antiviral drugs in the Hiv-positive patient

Successful treatment of hepatitis C virus (HCV) infection is necessary for the survival of HIV-infected patients. This review covers the outcomes of current therapy, first-generation HCV direct-acting antivirals (DAAs) and their drug-to-drug interactions (DDIs). Understanding DDIs between HIV antiretroviral therapy (ART) and the DAAs in development is important to assure the best management of the HIV/HCV coinfected individuals. The two first-in-class DAAs were approved for clinical use in 2011. The first trials with boceprevir or telaprevir added to standard therapy in HIV/HCV coinfected patients revealed triple therapy to be efficacious with significantly improved sustained virological response rates. However, these DAAs were associated with more and worse adverse effects, as well as with significant DDIs with multiple drugs, including ART. Early data on DAAs in development suggest improved efficacy and safety and the potential for lesser DDIs. Anti-HCV therapy is fundamental in coinfected patients, but the approved therapies are suboptimal. The first-generation of approved HCV DAAs improved efficacy of therapy in coinfected patients, but have multiple safety concerns, including potentially serious drug interactions with ART. Early results from newer DAAs are promising.