In addition, we observed a low discordance rate regarding genotyping when NS5a, 5′UTR and NS5b see more sequences were compared. Disclosures: Daniel P. Webster – Grant/Research Support: ViiV; Speaking and Teaching: Janssen, BMS The following people have nothing to disclose: Adele L. McCormick, Lawrence T. Wang, Ana Garcia-Diaz, Malcolm J. Macartney, Tim C. Conibear, Clare L. Booth, Dianne N. Irish, Tanzina Haque Introduction: Aim of this study was to examine early kinetics of HCV-RNA decay and quasispecies rearrangements during telaprevir (TVR)-based

triple therapy in treatment experienced and/or cirrhotic HCV-patients, providing insights into viral dynamics underlying viral failure. Methods: HCV-RNA decay (detection limit=15 IU/ml) was assessed per protocol and at early time points (1h-2h-3h-4h-5h-6h-8h-12h-24h-28h-48h-1w2w), and modeled according to Neumann et al., Science 1998. NS3-protease sequences were obtained during TVRtreatment (baseline-8h-24h-48h) by both population sequencing and ultradeep 454-pyrosequencing (UDPS). Results: Sixteen HCV-infected patients (GT1 b=11; GT1 a=5) received TVR+peglFN/RBV after previous failure this website to peglFN/RBV-treatment (non-responders=9; relapsers=5) or as first-line regimen (N=2). Both naīve patients and 4/9(44.4%)

previous nonresponders were cirrhotic. HCV-RNA decay was biphasic, starting after 6h since first-dose (median[IQR] decay=0.6[0.4-1.0] logIU/ml). In all patients, independently from previous treatment experience or HCV-genotype, phase I decay was rapid, with a median[IQR] of 2.4[2.2-2.7] loglU/ml decrease in the first 24h and 2.8[2.6-3.2] loglU/ml in 48h. The median virion clearance rate (c) was 9.8 day-1 (8.0 day-1 with IFNa2b+RBV), and virion half-life was 2.0 h. Phase II decay was characterized by a median cell clearance rate (5) of 0.30 day1(0.14 day-1 with IFN-a2b+RBV) and a median[IQR] 2w HCVrNa drop of 4.3[3.6-4.6] LoglU/ml. At 2w, a cut-off value of 100 IU/ml divided patients into two groups, with a significantly

different median[IQR] HCV-RNA decay from baseline: 3.3[2.0-LoglU/ml in the 4 patients with >100 IU/ml vs.4.5[4.2-LoglU/ml in the 10 patients with <100 IU/ml (p<0.01). Notably, 3/3 failing patients had HCV-RNA>100 IU/ml vs.0/5 patients who reached End Of Treatment SPTLC1 (EOT) (p=0.02). By UDPS, failing patients showed an increase in nucleotide NS3 quasispecies variability after 24h of treatment (baseline mean[0SD] evolutionary divergence=0.012±0.003 nsubs/site vs.0. 025±0.004 nsubs/site at 24h; p<0.01), less seen in EOT patients (baseline=0.010±0.002 vs.24h=0.012±0.002 nsubs/site; p=0.70). At the amino acid level, the dominant strain remained invariant in all patients (prevalence>98%). Conclusions: Triple therapy administration affects viral dynamics with an extent of first phase decline and an acceleration of second phase, mediated by the higher effectiveness of DAAs.