The aim of this study was to determine if baseline analysis of the NS3 viral region using ultra-deep pyrosequencing (UDPS) could help to predict SVR to triple therapy. Methods: Forty genotype 1 patients failing to achieve a SVR with Peg-IFNa + Ribavirin combination
(null responders: n=18; partial responders: n=14, relapsers: n=8 and retreated with triple therapy adding BOC or TPV were included. Their main characteristics were: mean age 55+/-8 years, 47.5% subtype 1a, 77.5% F3-F4. Baseline UDPS of the NS3-protease viral gene was performed on plasma and peripheral blood mononuclear cells (PBMC). Sequences obtained were analyzed in terms of resistance mutations with a threshold of 1% determined by using a control this website transcript. Heterogeneity of quasispecies was evaluated by the calculation of Shannon Entropy (SE). Results: Baseline mutations were found in 4 patients who achieved SVR with triple Selleckchem HKI 272 therapy and in 4 patients who did not. For these last patients, mutations were already major in three patients and persisted
until viral breakthrough. In the fourth patient, the mutated population accounted for only 1.4% of the total viral population at baseline but dramatically rose upon failure. In two patients, minor mutations were found in PBMC while not in plasma, and corresponded to mutations observed at the viral rebound. Compartmentalization between plasma and PBMC was confirmed with the analysis of the obtained sequences. More broadly, the NS3 quasipecies heterogeneity expressed
as SE was significantly lower at baseline in patients achieving SVR compared MCE公司 to nonSVR (SE= 26.98016.64 x 10-3 vs 44.93 ± 19.58 x 10-3, p=0, 0049). By multivariate analysis, independent predictors of SVR were F0F2 fibrosis stage (OR =13.3, CI95% 1.25141.096, p<0.03) and SE below median value (oR=5.4, CI95% 1.22-23.87, p<0.03). Conclusion: More than the presence of baseline minor mutations in plasma or in PBMC, NS3 viral heterogeneity determined by UDPS is an independent factor of SVR in previously treated patients receiving a triple therapy with an anti-protease drug. This parameter could be included in a score predicting response to therapy. Disclosures: Jean-Pierre H.