Resistance to hepatitis C virus protease inhibitors

Significant scientific advances have enabled the development of new classes of antivirals for the treatment of HCV. Protease inhibitors were the first approved, achieving substantially higher response rates, with shorter treatment durations, in the majority of genotype 1 infected patients. However, in patients who fail treatment, drug resistant variants frequently emerge. The pattern of resistant variants observed is a result of the specific inhibitor, viral subtype, and level of drug selective pressure. Data suggest the replacement of these variants over time; however, retreatment of these patients is an area of needed investigation. As multiple drug classes progress in development, combinations of agents improve treatment success, increase the genetic barrier to resistance, and provide shorter treatment durations for diverse patient populations.