Interferon-Free Therapy for HCV Genotype 1 in a Difficult-to-Treat Population

Recent studies demonstrate the efficacy of an interferon-based sofosbuvir regimen for genotype 1 hepatitis C virus (HCV) infection and an interferon-free sofosbuvir regimen for genotype 2 and possibly genotype 3 HCV infections (NEJM JW Gastroenterol Apr 23 2013and NEJM JW Gastroenterol May 24 2013). Now, researchers have evaluated the safety and efficacy of an interferon-free regimen in patients with HCV genotype 1 infection who have host or viral factors associated with poor treatment outcomes.

In this single-center, open-label, phase II study, investigators randomized 60 patients to sofosbuvir (400 mg daily) plus a weight-based (1000–1200 mg daily) or fixed (600 mg daily) dose of ribavirin (RBV) for 24 weeks. The primary endpoint was sustained virologic response at week 24 (SVR24). Factors previously associated with poor treatment outcomes in the study population included HCV genotype 1a (70%), advanced fibrosis (24%), body-mass index >30 kg/m² (49%), and black race (80%).

The overall SVR24 rate was higher in those receiving the weight-based versus the fixed-dose RBV regimen (68% vs. 48%; P=0.20). The lower rate in the fixed-dose group was driven by a high rate of relapse. In multivariate analysis, male sex, advanced liver disease (all patients with cirrhosis and 54% of advanced fibrosis patients relapsed), and high baseline HCV RNA (>800,000 IU/mL) were associated with relapse. No associated resistance was identified. Adverse effects were mild and did not result in any discontinuations.