José M. Ladero
Treatment response remains suboptimal for many patients with chronic hepatitis C, particularly those with genotype 1 and high levels of viremia. The efficacy of high-dose regimens of peginterferon α-2a and ribavirin was compared with conventional dose regimens in patients with features predicting poor treatment responses. Eligible treatment-naïve adults with genotype 1 infection, hepatitis C virus (HCV) RNA > 800,000 IU/ mL and body weight > 85 kg were randomized to double- blind treatment with peginterferon α-2a at 180 or 270 microg/week plus ribavirin at 1,200 or 1,600 mg/ day for 48 weeks (four regimens were evaluated). The primary endpoint was viral kinetics during the first 24 weeks of therapy. Among patients receiving peginterferon α-2a (270 microg/week) the magnitude of HCV RNA reduction was significantly greater than for patients randomized to the conventional dose of peginterferon α-2a (180 microg/week) for the pairwise comparison for ribavirin at 1,600 mg/day (P = 0.036) and numerically greater for the pairwise comparison for ribavirin at 1200 mg/day (P = 0.060). Patients randomized to the highest doses of peginterferon α-2a (270 microg/week) and ribavirin (1,600 mg/day) experienced the numerically highest rates of sustained virologic response (HCV RNA < 50 IU/mL) and the lowest relapse rate (47% and 19%, respectively). The arm with the higher doses of both drugs was less welltolerated than the other regimens. Conclusion: Higher fixed doses of peginterferon alfa-2a (270 microg/ week) and ribavirin (1600 mg/day) may increase sustained virologic response rates compared with lower doses of both drugs in patients with a cluster of difficult- to-treat characteristics.