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41 Differences in treatment outcome to antiviral therapy based on genotype and viral load in hepatitis C genotypes 2 and 3 in the Win-R trial

2006; Elsevier BV; Volume: 44; Linguagem: Inglês

10.1016/s0168-8278(06)80042-5

1600-0641

R.S. Brown, Ira M. Jacobson, Nezam H. Afdhal, B. Freilich, Marketa Pauley, Fredric Regenstein, Steven L. Flamm, Paul Y. Kwo, Louis Griffel, Clifford A. Brass,

Hepatitis B Virus Studies

Background: Genotype 2 (G2) and 3 (G3) chronic hepatitis C virus (HCV) have high sustained virologic response (SVR) rates to peginterferon (PEG-IFN) alpha and ribavirin and require shorter duration of treatment.The optimal dosing of ribavirin and differences between SVR in G2 and G3 is undefined.Objective: To determine the predictors of response to PEG-IFN alpha-2b plus ribavirin in patients with HCV G2 and G3.Methods: a multicenter, randomized, investigatorinitiated trial in 225 US sites between 12/00 and 6/05 randomized treatment-naive adults HCV patients with compensated liver disease to receive PEG-IFN alpha-2b 1.5 gg/kg/week plus FD ribavirin (800 mg/day) or WBD ribavirin (800 mg/day for weight 85 105 kg, 1400 mg/day for >105 125 kg).G2 and G3 patients were also randomized to receive 24 or 48 weeks of therapy.HCV RNA was assessed at weeks 0, 24, 48 and 72.The primary endpoint was SVR (absence of detectable HCV RNA at week 72) in patients ~>65 kg.Results: 1829 G2/3 patients were enrolled and randomized to WBD (24wksn 317,48wksn 602)orFD(24wksn 322, 48 weeks n 588).SVR rates were similar in the WBD and FD groups (68% vs. 65%) and were similar but lower with 48 weeks than 24 weeks due to greater dropout with missing data (SVR not known, treated as NR).G2 had a higher SVR and lower relapse rate than G3 (72% vs. 59% with 24 weeks of therapy and 5% vs. 10%, respectively).G3 patients had higher SVR with WBD (57% vs. 52%) but not statistically significantly.Relapse rates were highest in G3 high viral load patients treated for 24 weeks (16%).Multivariate analyses revealed G2, less advanced fibrosis, and 24 weeks of therapy as significant predictors of SVR.Safety and rates of drug discontinuation were similar between the groups.Conclusions: With PEG-IFN alpha-2b, WBD ribavirin and 48 weeks of therapy offers less advantage to FD in patients with HCV genotype 2 and 3. SVR rates are lower for G3 patients who appear to benefit from higher ribavirin dosing.