Overview of direct-acting antiviral drugs and drug resistance of hepatitis C virus

Abstract

The advent of direct-acting antivirals (DAAs) has brought about a sudden renaissance in the treatment of chronic hepatitis C virus (HCV) infection with SVR rates now routinely >90%. However, due to the error-prone nature of the HCV RNA polymerase, resistance-associated substitutions (RASs) to DAAs may be present at baseline and can result in a significant effect on treatment outcomes and hamper the achievement of sustained virologic response. By further understanding the patterns and nature of these RASs, it is anticipated that the incidence of treatment failure will continue to decrease in frequency with the development of drug regimens with increasing potency, barrier to resistance, and genotypic efficacy. This review summarizes our current knowledge of RASs associated with HCV infection as well as the clinical effect of RASs on treatment with currently available DAA regimens.