Treatment of HCV in Patients who Failed First-Generation PI Therapy: a Review of Current Literature.

The addition of the first direct-acting antiviral agents, the NS3 protease inhibitors boceprevir or telaprevir, to peg interferon and ribavirin was a major advance in the treatment of genotype 1 hepatitis C individuals with sustained virological response (SVR) rates of 63-75 %. Those who did not achieve SVR had high rates of resistance-associated variants against NS3 protease domain. Retreatment options for those who have failed first-generation protease inhibitors generally are guided by retreatment with direct-acting antiviral agents from other classes. Phase 2 and phase 3 data have demonstrated that retreatment with 12-24 weeks of a NS5B inhibitor (sofosbuvir) in combination with a NS5a inhibitor (daclatasvir or ledipasvir) with or without ribavirin can achieve SVR at high rates comparable to treatment-naive individuals.