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-naive patients with chronic hepatitis C

We determined whether triple therapy comprising amantadine (AMA), ribavirin (RBV) and either peginterferon (PEG-IFN) alpha- 2a or conventional IFN alpha- 2a would improve sustained virological response ( SVR) rates over dual therapy with IFN alpha-2a and RBV in patients with chronic HCV infection. A total of 362 treatment-naive patients were randomized to 48 weeks of treatment with: PEG-IFN alpha-2a 180 mu g/ week ( group A) or IFN alpha-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-naive patients with chronic hepatitis C, triple therapy with PEG-IFN alpha-2a, RBV and AMA produces higher SVR than dual or triple therapy with conventional IFN alpha-2a.