• Stephen Pianko, Steven L Flamm, Mitchell L Shiffman, Sonal Kumar, Simone I Strasser, Gregory J Dore, John McNally, Diana M Brainard, Lingling Han, Brian Doehle, Erik Mogalian, John G McHutchison, Mordechai Rabinovitz, William J Towner, Edward J Gane, Catherine A M Stedman, K Rajender Reddy, and Stuart K Roberts.
• Ann. Intern. Med. 2015 Dec 1; 163 (11): 809-17.

BackgroundEffective treatment options are needed for patients with genotype 1 or 3 hepatitis C virus (HCV) infection in whom previous therapy has failed.ObjectiveTo assess the efficacy and safety of sofosbuvir plus velpatasvir, with and without ribavirin, in treatment-experienced patients.DesignRandomized, phase 2, open-label study. (ClinicalTrials.gov: NCT01909804).Setting58 sites in Australia, New Zealand, and the United States.PatientsTreatment-experienced adults with genotype 3 HCV infection without cirrhosis (cohort 1) and with compensated cirrhosis (cohort 2) and patients with genotype 1 HCV infection that was unsuccessfully treated with a protease inhibitor with peginterferon and ribavirin (50% could have compensated cirrhosis) (cohort 3).InterventionAll patients received 12 weeks of treatment that included 400 mg of sofosbuvir once daily. Patients in each cohort were randomly assigned to 25 mg of velpatasvir once daily with or without ribavirin or 100 mg of velpatasvir once daily with or without ribavirin.MeasurementsProportion of patients with sustained virologic response at week 12 after treatment (SVR12).ResultsIn cohort 1, SVR12 rates were 85% with 25 mg of velpatasvir, 96% with 25 mg of velpatasvir plus ribavirin, 100% with 100 mg of velpatasvir, and 100% with 100 mg of velpatasvir plus ribavirin. In cohort 2, SVR12 rates were 58% with 25 mg of velpatasvir, 84% with 25 mg of velpatasvir plus ribavirin, 88% with 100 mg of velpatasvir, and 96% with 100 mg of velpatasvir plus ribavirin. In cohort 3, SVR12 rates were 100% with 25 mg of velpatasvir, 97% with 25 mg of velpatasvir plus ribavirin, 100% with 100 mg of velpatasvir, and 96% with 100 mg of velpatasvir plus ribavirin. The most common adverse events were headache, fatigue, and nausea.LimitationTreatment assignments were not blinded, and no inferential statistics were planned.ConclusionTreatment with 400 mg of sofosbuvir plus 100 mg of velpatasvir for 12 weeks was well-tolerated and highly effective in treatment-experienced patients with genotype 1 or 3 HCV infection.Primary Funding SourceGilead Sciences.

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