Beyond telaprevir and boceprevir: resistance and new agents for hepatitis C virus infection

The addition of the hepatitis C virus (HCV) protease inhibitors telaprevir and boceprevir to peginterferon alfa with ribavirin therapy has increased cure rates in HCV infection. Numerous other direct-acting antivirals (DAAs) are in advanced stages of development, including next-generation protease inhibitors, nonstructural protein (NS) 5A inhibitors, and nonnucleoside and nucleos(t)ide NS5B polymerase inhibitors. The classes have different potencies, different resistance mutation profiles, and different barriers to the emergence of resistance. A comprehensive table of resistance mutations for classes of DAAs is presented. Numerous combinations of DAAs with or without ribavirin have been evaluated in early studies of interferon alfa-free regimens, with results indicating that cure is indeed possible with such therapy and suggesting that identification of regimens that could produce cure in the majority of patients may occur within the foreseeable future. This article summarizes a presentation by David L. Wyles, MD, at the IAS-USA live continuing medical education activity held in New York in June 2012.