Sofosbuvir for the treatment of hepatitis C virus infection

Results of published phase III trials of sofosbuvir in combination with ribavirin or peginterferon-ribavirin are summarized in Appendix 1 (available at www.cmaj.ca/lookup/suppl /doi: 10.1503/cmaj.l40151/-/DCl). In the NEUTRINO trial, 5 327 treatment- naive patients with HCV infection received sofosbuvir plus peginterferon-ribavirin for 12 weeks. Most (89%) had HCV genotype 1 infection, and the remainder had HCV genotype 4, 5 or 6 infection. The sustained virologic response rate at 12 weeks was 90%. Among patients with cirrhosis, the sustained virologic response rate was 80%, which is the highest rate reported in that population. Sofosbuvir in combination with ribavirin was investigated in treatment-naive patients with HCV genotype 2 or 3 infection in the FISSION trial, an open-label randomized active-control trial.5 A sustained virologic response rate of 67% at 12 weeks was observed in both the sofosbuvir-ribavirin and the peginterferon- ribavirin arms. In the POSITRON trial,6 patients with HCV genotype 2 or 3 infection who were intolerant of or ineligible for interferon treatment were randomly assigned to either the sofosbuvir-ribavirin ann or the matching placebo arm. The sustained virologic response rate at 12 weeks was 78% in the intervention group and 0% in the placebo group. The data pertaining to sofosbuvir support its use as part of combination therapy in the treatment of chronic HCV genotype IM infection. Whether combined with ribavirin alone, with peginterferon and ribavirin, or with other direct-acting antiviral agents, sofosbuvir will likely have a large impact on the treatment of HCV infection. Studies assessing the safety and efficacy of sofosbuvir in traditionally difficult-to-treat populations (e.g., patients receiving liver transplantation or hemodialysis, people with hemophilia and those with HIV/HCV co-infection) are currently underway. Combinations of sofosbuvir with other direct-acting antiviral agents are also being evaluated.11-14 Other promising interferon-free combinations that do not involve sofosbuvir are also in development.