Interferon-free Sofosbuvir/Ribavirin combo appears effective in Hepatitis C Genotype 1

‘Big 4’ Journal Highlights – Journal of the American Medical (JAMA) – by Bruce Sylvester -Among patients with unfavorable treatment characteristics, treating chronic hepatitis C virus (HCV) genotype 1 infection with the interferon-free regimen of sofosbuvir and ribavirin has resulted in a high sustained virologic response rate, researchers reported on August 28, 2013 in of the Journal of the American Medical Association/JAMA.

Anuoluwapo Osinusi, M.D., M.P.H., of the (US) National Institutes of Health in Bethesda, Maryland, and colleagues evaluated the efficacy of sofosbuvir administered in combination with once-daily ribavirin in a treatment-naive population with unfavorable characteristics of treatment success.

Dr. Osinusi and colleagues noted, “The HCV epidemic in the United States is centered in large urban areas among populations with a high prevalence of unfavorable traditional predictors of treatment response. Recent studies show that interferon-free, directly acting antiviral agent-only regimens can successfully achieve sustained virologic response (SVR); however, populations traditionally associated with poorer treatment outcomes have been underrepresented.”

The investigators in the 2-part, phase II study enrolled 60 subjects patients with HCV genotype 1. The subjects were enrolled from October 2011-April 2012.

In part 1 of the study, 10 subjects with early to moderate liver fibrosis were treated with 400 mg/d of sofosbuvir and weight-based ribavirin for 24 weeks. In part 2, 50 participants with all stages of liver fibrosis were randomized 1:1 to receive 400 mg of sofosbuvir with either weight-based or low-dose 600 mg/d of ribavirin for 24 weeks.

The primary outcome was the proportion of subjects achieving undetectable HCV viral load 24 weeks after treatment ended (sustained virologic response of 24 weeks [SVR24]).

Eighty-three percent of the subjects were black. Sixty-six percent were male, and 23 percent had advanced liver disease.

Twenty-four participants (96 percent) in each group achieved viral suppression by week 4. Seven subjects, 28 percent, in the weight-based group and 10 subjects, 40 percent, in the low-dose group relapsed after ending treatment , leading to SVR24 rates of 68 percent in the weight-based group and 48 percent in the low-dose group.

Baseline factors of male sex, advanced liver disease, and high baseline HCV RNA levels were associated with relapse.

The combination regimen was safe and generally well tolerated.

The authors concluded, “This study demonstrates the efficacy of an interferon-free regimen in a traditionally difficult-to-treat population while exploring the reasons for treatment relapse. In this study, treatment of chronic HCV infection with a single directly acting antiviral agent (sofosbuvir) and weight-based ribavirin resulted in a high SVR rate in a population with unfavorable traditional predictors of treatment response compared with reported rates with currently used interferon-based therapy in similar populations.”