Effectiveness and Safety of Sofosbuvir-Based Regimens for Chronic HCV Genotype 3 Infection: Results of the HCV-TARGET Study

Abstract

Background: Sofosbuvir (SOF) is active against all hepatitis C virus (HCV) genotypes, and SOF-based therapies lead to high rates of sustained virologic response (SVR). However, genotype 3 (GT3) HCV remains a challenge with lower SVR rates reported, particularly in patients with cirrhosis. This study reports the effectiveness and safety of SOF-based therapy in patients with GT3 HCV treated in clinical practice.

Methods: Hepatitis C Virus Therapeutic Registry and Research Network is an international, prospective observational study evaluating patients treated in usual clinical practice. Patients with GT3 HCV were analyzed to assess predictors of treatment response and adverse events using descriptive statistics and multivariable logistic regression.

Results: Treatment outcomes were available for 197 patients treated with SOF and ribavirin (RBV), with or without peginterferon, including 54% with cirrhosis and 49% who failed prior therapy. Of 178 patients treated with SOF/RBV, 60% achieved SVR at 12 weeks (SVR12), compared with 84% of 19 patients treated with SOF/peginterferon/RBV. For patients treated with SOF/RBV, the SVR12 rate was 58% in treatment-naive patients with cirrhosis, and 42% in those with cirrhosis who failed prior therapy. In noncirrhotic patients, SVR12 rates were 89% in treatment-naive and 88% in treatment-experienced patients. After controlling for age and sex, absence of cirrhosis (odds ratio [OR], 6.4; 95% confidence interval [CI], 2.78-14.74), albumin levels ≥3.2 g/dL (OR, 12.48; 95% CI, 3.86-40.33), and platelet count >10(5) cells/µL (OR, 7.44; 95% CI, 3.51-15.78) were associated with greater odds of SVR12 CONCLUSIONS: SVR rates were acceptable in patients with GT3 HCV without cirrhosis; however, in those with cirrhosis, treatment with SOF/RBV was suboptimal, highlighting the need for new therapies for this population.

Keywords: cirrhosis; genotype 3; interferon; ribavirin; sofosbuvir.

Figure 1.

Baseline predictors of sustained virologic response (SVR) among patients with genotype 3 hepatitis C virus treated with sofosbuvir (SOF) and ribavirin (RBV) with or without peginterferon with available virologic outcomes. Factors associated with SVR are shown with an estimate of the odds ratios (ORs) with 95% confidence interval determined by multivariable logistic regression for each variable controlled for either age and sex**, or age or sex*. Abbreviations: CrCl, creatinine clearance; HGB, hemoglobin; LCL, lower confidence limit; TBIL, total bilirubin; UCL, upper confidence limit.

Figure 2.

Baseline predictors of sustained virologic response (SVR) among patients with genotype 3 hepatitis C virus and cirrhosis treated with sofosbuvir (SOF) and ribavirin (RBV) with or without peginterferon with available virologic outcomes. Factors associated with SVR among patients with cirrhosis are shown with an estimate of the odds ratios (ORs) with 95% confidence interval determined by multivariable logistic regression for each variable controlled for either age and sex**, or age or sex*. Abbreviations: CrCl, creatinine clearance; HGB, hemoglobin; LCL, lower confidence limit; MELD, Model for End-Stage Liver Disease; TBIL, total bilirubin; UCL, upper confidence limit.

Figure 3.

Correlation of probability of sustained virologic response at 12 weeks (SVR₁₂) and initial ribavirin (RBV) dose (by body weight [BW]; mg/kg). The impact of the initial dose of RBV is shown by estimating the probability of SVR according to initial RBV dose using observed SVR (circle) and observed virologic failure (diamond), The shaded area shows the 95% confidence interval (CI) for the estimated correlation.