Treatment of chronic hepatitis C virus (HCV) genotype 1 infection with the interferon-free regimen of sofosbuvir and ribavirin resulted in a high sustained virologic response rate in a patient population with unfavorable treatment characteristics, according to a study in the August 28 issue of JAMA.
"Chronic infection with hepatitis C virus is a major cause of chronic liver disease, end-stage liver disease, hepatocellular cancer and remains the leading indication for liver transplants in western countries. 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," according to background information in the article. "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."
Anuoluwapo Osinusi, M.D., M.P.H., of the National Institutes of Health, Bethesda, Md., and colleagues evaluated the efficacy of sofosbuvir administered in combination with weight-based or low-dose once daily ribavirin in a treatment-naive population with unfavorable characteristics of treatment success. The randomized, 2-part, phase 2 study included 60 patients with HCV genotype 1 enrolled from October 2011-April 2012. In the study's first part, 10 participants with early to moderate liver fibrosis were treated with 400 mg/d of sofosbuvir and weight-based ribavirin for 24 weeks. In the second part, 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 participants with undetectable HCV viral load 24 weeks after treatment completion (sustained virologic response of 24 weeks [SVR24]). Eighty-three percent of the participants were black; 66 percent, men; and 23 percent had advanced liver disease.
Twenty-four participants (96 percent) in each group achieved viral suppression by week 4. "A total of 7 participants (28 percent) in the weight-based group and 10 (40 percent) in the low-dose group relapsed after treatment completion leading to SVR24 rates of 68 percent in the weight-based group and 48 percent in the low-dose group," the authors write.
The combination regimen was safe and well tolerated with no death or discontinuation of treatment due to adverse events. The most frequent adverse events were headache, anemia, fatigue, and nausea, the severity of which ranged from mild to moderate.
The researchers also found that the baseline factors of male sex, advanced liver disease, and high baseline HCV RNA levels were associated with relapse.
"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."
(JAMA. 2013;310(8):804-811; Available pre-embargo to the media at http://media.jamanetwork.com)
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