Mullen this website – Advisory Committees or Review Panels: GILEAD; Speaking and Teaching: GILEAD Andrea D. Branch – Grant/Research Support:

Kadmon, Gilead, Janssen Damaris C. Carriero – Consulting: Genentech, Gilead, Vertex; Speaking and Teaching: Genentech, Vertex The following people have nothing to disclose: Daniel S. Fierer, Alison J. Uriel, Wouter O. van Seggelen, Rosanne M. Hijdra, David Cassagnol BACKGROUND: Since 2011 recommended treatment for HCV genotype 1 has been pegIFN/RBV combined with TVR or BOC. However, adherence to current response guided therapy (RGT) and the effectiveness of triple therapy outside of registration trials are poorly defined. AIMS: To assess utilization of RGT and virologic responses for a large cohort of pts treated within the U. S. based upon local practice and HCV RNA determinations. METHODS: HCV-TARGET is an ongoing longitudinal observational study at 44 academic and 59 community centers. Demographic, clinical and virologic data and adverse events are collected throughout treatment and follow-up on sequentially enrolled pts, together with information on adherence to treatment futility rules at key time points. RESULTS: Of 2,212 GW-572016 in vivo pts enrolled

in TARGET, 709 have been followed for at least 1 yr, of whom 524 had a determination of virologic outcome within a window up to 6 wks after stopping therapy (SVR6). Of 524 pts, 61% were male, 77% Caucasian (17% Black). Their mean age was 56 yrs (range 18-76), 41% were treatment naive and 44% cirrhotic. Adherence to futility rules was evaluated: an HCV RNA result was available at wk 4 in 84% of pts on TVR and in 73% of pts on BOC by wk 12.Among pts on TVR, 19/457

(4%) had HCV RNA >1000 IU at treatment wk 4; 7 (37%) promptly discontinued treatment, 9 (47%) discontinued later (mean medchemexpress −7.8 wks) but 3 remained on treatment and 1 achieved SVR6.Of pts with a planned BOC regimen, 12 had an inadequate viral response to pegIFN/RBV by wk 4 so treatment was discontinued. By wk 8, HCV RNA declined <3 log10 from baseline in 12/142 (8%) on BOC; 5 (42%) promptly discontinued treatment, while 7 (68%) continued. By wk 12 on BOC, 16/123 (13%) met the futility rule (residual HCV RNA >100 IU). Of these, 7 (58%) stopped therapy within 2 wks, 6 continued (mean +5.5 wks; range 3-12 wks), 3 completed a full course of treatment, although only 1 achieved SVR6.Table shows rates of SVR6.CONCLUSIONS: RGT virologic milestones appeared to be managed appropriately in most pts. Preliminary SVR results were lower than in published pivotal studies, possibly because pts in this large cohort had difficult-totreat characteristics (cirrhosis, genotype 1a, prior null response).