Background: In this Phase IIIb study, we evaluated the efficacy and safety of the oral nucleotide analogue inhibitor sofosbuvir plus ribavirin, with special attention given to viral resistance, in Russian patients with HCV genotype-1 or -3.
Methods: Treatment-naive patients with and without compensated cirrhosis were randomized (1:1) to receive 16 or 24 weeks of once-daily sofosbuvir 400 mg plus twice-daily oral ribavirin 1,000 or 1,200 mg/day. The primary efficacy end point was the proportion of patients with sustained viral response 12 weeks after the end of treatment (SVR12). Viral resistance testing was performed by deep sequencing on all baseline samples and for patients who experienced virological failure.
Results: SVR12 rates for patients with genotype-1 HCV were 50% and 76% for those in the 16-week and 24-week groups, respectively, and for patients with genotype-3 HCV, SVR12 rates were 87% and 90% for patients in the 16-week and 24-weeks groups, respectively. Genotype-1 patients with the L159F resistance-associated variant who received 16 weeks of treatment had lower SVR12 rates than those without, but in patients who received 24 weeks of treatment, response rates were similar in those with and without L159F (80% versus 74%). Sofosbuvir plus ribavirin was well tolerated with no deaths, adverse event-related study drug discontinuations, or grade 3 or 4 adverse events, and few grade 3 or 4 laboratory abnormalities.
Conclusions: Sofosbuvir plus ribavirin for 16 or 24 weeks was associated with a high SVR rate in patients with HCV genotype-3. Among HCV genotype-1b patients, the presence of the L159F variant at baseline was associated with a lower SVR rate in those treated for 16 weeks but not in those treated for 24 weeks. Sofosbuvir plus ribavirin was safe and well tolerated regardless of treatment duration. Clinicaltrials.gov number NCT01896193.