Mechanisms of Virologic Failure with Direct-Acting Antivirals in Hepatitis C and Strategies for Retreatment

Abstract

The current standard of care for hepatitis C therapy is the combination of direct-acting antiviral (DAA) agents. These orally administered medications target the viral proteins and halt the hepatitis C virus lifecycle. Despite high cure rates with these novel drugs, virologic failure with DAAs are of mounting concern as real-world sustained virologic response 12 rates seem lower than expected. The mechanisms of virologic failure to DAAs are likely multifactorial, including baseline resistance variants, the efficacy of the agents used, and host factors. Salvage therapy for DAA virologic failures is an area of emerging research.

Keywords: Direct-acting antivirals (DAAs); Genotype 1; Hepatitis C; NS5A inhibitor; Protease inhibitor; RNA-polymerase inhibitor; Resistance-associated variants (RAVs); Retreatment.