Sofosbuvir (GS-7977) plus peginterferon/ribavirin in treatment-na?ve patients with HCV genotype 1: A randomized, 28-day, dose-ranging trial.

摘要

BACKGROUND & AIMS: Sofosbuvir (formerly GS-7977) is a pyrimidine nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B polymerase. We assessed the safety, tolerability, antiviral activity, and pharmacokinetics of sofosbuvir plus pegylated-interferon (PegIFN)/ribavirin (RBV) in a 28-day, dose-ranging trial in treatment-na?ve patients infected with genotype 1 HCV. METHODS: In this double-blind study, 64 patients were randomized (1:1:1:1) to receive one of three once-daily doses of oral sofosbuvir (100, 200, or 400mg) or placebo plus PegIFN/RBV for 28days, after which all patients continued to receive PegIFN/RBV alone for a further 44weeks. RESULTS: Patients in the sofosbuvir/PegIFN/RBV groups experienced mean reductions in HCV RNA >5log10IU/ml (-5.3 for 100mg, -5.1 for 200mg and -5.3 for 400mg) vs. -2.8log10IU/ml for placebo/PegIFN/RBV after 28days. Rapid virologic response (RVR) rates were markedly higher after sofosbuvir treatment (88-94%) than placebo (21%), as were rates of sustained virologic response (SVR) at post-treatment Week 24 (56%, 83%, and 80% for sofosbuvir 100, 200, and 400mg, respectively, vs. 43% for placebo). The number of patients experiencing virologic breakthrough and post-treatment relapse was higher in the sofosbuvir 100mg group than sofosbuvir 200 and 400mg groups. Sofosbuvir was well tolerated; the most frequent adverse events were fatigue and nausea. CONCLUSIONS: These results support further studies with sofosbuvir at 200mg and 400mg to determine the optimal dose and treatment duration of sofosbuvir in HCV genotype 1.