1. Among patients with hepatitis C virus (HCV) genotype 2 or 3, 12 weeks of treatment with a once-daily, fixed-dose, combination tablet of sofosbuvir-velpatasvir resulted in rates of sustained virologic response compared to those treated with standard therapy.
2. The results from this study provide the potential for using ribavirin-free regimens given the knowledge that ribavirin has a high side effect profile.
Evidence Rating Level: 1 (Excellent)
Study Rundown: This is a report of two randomized, controlled trials involving patients with HCV genotype 2 and 3 infection, including patients with compensated cirrhosis. In the HCV genotype 2 trial, patients were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir for 12 weeks or sofosbuvir plus weight-based ribavirin for 12 weeks. In the HCV genotype 3 trial, patients were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir for 12 weeks or sofosbuvir-ribavirin for 24 weeks. The results showed that Sofosbuvir-velpatasvir demonstrated a significantly higher rate of sustained virologic response than sofosbuvir-ribavirin at 12 weeks after the end of therapy in patients chronically infected with HCV genotype 2 and 3.
These studies drew strength from their randomized, controlled design and successfully meeting their target of enrolling 20% of patients that had compensated cirrhosis. However, they are limited by the investigators, patients, and trial personnel being aware of the treatment assignments at all points in the two trials. The generalizability of these results may be limited by the exclusion of patients with decompensated liver disease and the small number of black patients who were enrolled, as a result of the low prevalence of HCV genotype 2 or 3 infection among blacks in certain regions, including the United States.
Click to read the study, published today in NEJM
Relevant Reading: A phase 1, randomized, dose-ranging study of GS-5816, a once-daily NS5A inhibitor, in patients with genotype 1–4 hepatitis C virus
In-Depth [randomized controlled trial]: This study includes two multicenter trials, in which patients with chronic HCV infection were randomized in a 1:1 ratio to receive a fixed dose combination tablet containing 400 mg sofosbuvir + 100 mg velpatasvir OD for 12 weeks or 400 mg sofosbuvir OD and ribavirin (1000 mg in patients <75 kg and 1200 mg in patients ≥ 75 kg) BID for 12 weeks for patients with HCV genotype 2 or 24 weeks for patients with HCV genotype 3.
The primary end point for the HCV genotype 2 and HCV genotype 3 trial was a sustained virologic response, which was defined as an HCV RNA level of less than 15 IU/mL at 12 weeks after the end of treatment. Among HCV genotype 2 infected patients who underwent randomization and began treatment, a significantly higher number of those treated with sofosbuvir-velpatasvir for 12 weeks (99%; 95% [CI], 96 to 100%) demonstrated a sustained virologic response 12 weeks after the end of treatment versus patients who were treated with sofosbuvir-ribavirin for 12 weeks (94%; 95% [CI], 88 to 97%) (p=0.02). Among HCV genotype 3 infected patients who underwent randomization and began treatment, a significantly higher number of those treated with sofosbuvir-velpatasvir for 12 weeks (95%; 95% [CI], 92 to 98%) demonstrated a sustained virologic response 12 weeks after the end of treatment compared to those treated with sofosbuvir-ribavirin for 24 weeks (80%; 95% [CI], 75 to 85%) (p < 0.001).
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