A randomized controlled trial of pegylated interferon α-2a (40 KD) or interferon α-2a plus ribavirin and amantadine vs interferon α-2a and ribavirin in treatment-naïve patients with chronic hepatitis C

We determined whether triple therapy comprising amantadine (AMA), ribavirin (RBV) and either peginterferon (PEG-IFN) α-2a or conventional IFN α-2a would improve sustained virological response (SVR) rates over dual therapy with IFN α-2a and RBV in patients with chronic HCV infection. A total of 362 treatment-naïve patients were randomized to 48 weeks of treatment with: PEG-IFN α-2a 180 μg/week (group A) or IFN α-2a 3 MU tiw (groups B and C). All patients received RBV 1000 or 1200 mg/day and those in groups A and B received AMA 200 mg/day, SVR was defined as an undetectable HCV RNA after 24 weeks of untreated follow-up. At the end of therapy, 74.4% (95% CI 0.66-0.82) of patients in group A were HCV RNA-negative compared with 42.5% (95% CI 0.33-0.50) of those in group B(P = 0.0001) and 48.8% (95% CI 0.40-0.56) of those in group C. SVR was achieved in a significantly greater proportion of patients in group A compared with groups B and C: 65.3% (95% CI 0.53-0.56), 33.3% (95% CI 0.25-0.41) and 44.6% (95% CI 0.36-0.53; P = 0.0001) respectively. In patients with genotype 1. SVR rates were 55.2, 22.8 and 28.8% with the three regimens respectively. Factors independently associated with SVR were HCV genotype 2 or 3, therapy with PEG-IFN, female gender and age. In treatment-naïve patients with chronic hepatitis C, triple therapy with PEG-IFN α-2a. RBV and AMA produces higher SVR than dual or triple therapy with conventional IFN α-2a.