[620] CHARACTERIZATION OF PHARMACOKINETIC/PHARMACODYNAMIC PARAMETERS FOR THE NOVEL HCV POLYMERASE INHIBITOR A-848837

Viral load (VL) is an important predictor for treatment outcome in patients with chronic hepatitis C. A HCV-RNA cut-off of 800,000 IU/ml was used to define high and low pre-treatment VL in standard-interferon based therapy.Recently, Zeuzem et al. (AASLD 2006) proposed 400,000 lUiml (assessed with the COBAS TaQMan HCV assay) as optimal cut-ofto best discriminate low and high VL, based on the probability to achieve SVR in patients treated with peginterferon (PEG-IFN) alpha 2a+ribavirin (RBV).Our study aimed to analyze the predictive value of this cut-off in patients treated with PEG-IFN alpha 2b+RBV Patients and Methods: 3 I2 patients ( I 77 naives; I35 non-naives) consecutively treated with PEG-IFN alpha-2b+RBV, were included in this study.Patients with genotypes 1, 4 or 5 or non-responders were treated 48 weeks; naive patients infected with genotypes 2 and 3 were treated 24 weeks.Serum HCVRNA was measured using VERSANT HCV-RNA 3.0 (bDNA) (Bayer diagnostics). Results:In naive patients SVR rate was 54% (G 1: 43%; G 2-3: 72%; G 4: 48%).SVR in patients with VL (lU/ml) <400,000 vs >400,000, <600,000 vs >600,000 and <800,000 vs >800,000, respectively, was:all naive patients: 73% vs 43%; 64% vs 44% and 60% vs 45%; -genotype 1: 63% vs 37%; 55% vs 36% and 51% vs 38%; -genotype 2-3: 86% vs 63%; 79% vs 66% and 77% vs 66% SVR rates were similar for all the three cut-offs in patients with high VL.In the 135 non-naive patients SVR rate was 38% (G I : 3 I%; G 2-3: 72%).SVR in patients with VL (IU/ml) <400,000 vs >400,000, <600,000 vs >600,000 and <800,000 vs > 800,000, respectively, was: 40% vs 37%; 41% vs 36% and 43% vs 35%.Conclusions: Similarly to PEG-IFN alpha-2a+RBV therapy, the optimal pretreatment VL cut-off(assessed with VERSANT HCV-RNA 3.0 (bDNA) for the best prediction of treatment outcome is 400,000 IU/ml, in naive patients (mainly genotype 1) treated with PEG-IFN alpha-2b+RBV This cut-off is not efficient for non-naive patients.16191