Retreatment with sofosbuvir plus grazoprevir/elbasvir plus ribavirin of patients with hepatitis C virus genotype 1 or 4 who previously failed a NS5A or NS3-containing regimen. ANRS HC34 REVENGE

Abstract

Failure to achieve sustained virological response (SVR) with hepatitis C virus (HCV) direct-acting antiviral-based regimens is commonly associated with emergence of resistance-associated substitutions (RAS). Re-treatment of patients who failed prior direct-acting antivirals remain challenging. The aim of this prospective and randomized study was to evaluate the efficacy (SVR12 primary endpoint) and safety of sofosbuvir + grazoprevir/elbasvir + ribavirin for 16 or 24 weeks in patients who had failed to achieve SVR on previous NS5A or NS3-based therapy and with evidence of RAS at failure. Patients were chronically infected with HCV genotype (GT) 1 or 4. Most of them had advanced fibrosis or compensated cirrhosis (liver stiffness 5.8–48.8 kPa). All patients achieved HCV RNA below lower limit of quantification (either TD[u] or TND) during treatment. SVR12 was achieved by 25/26 patients. The only patient who did not reach SVR was a patient who died but HCV-RNA was negative at this time (5 weeks after stopping treatment). No patient discontinued treatment because of adverse events or virological failure. Globally, treatment was well tolerated. In conclusion, our findings support the concept of retreating with sofosbuvir+ grazoprevir/elbasvir + ribavirin for 16 weeks GT1 or GT4 DAA-experienced patients with proven NS5A or NS3 RAS.