1% (48 of 133) with placebo/PR (Table 2, Figure 1A). The difference between the 2 groups (controlling for HCV 1 subtype and IL28B genotype as stratification factors) was statistically significant at 43.8% (95% CI, 34.6–53.0; P < .001). The majority of simeprevir-treated patients (92.7%; 241 of 260) met RGT criteria to complete treatment at week 24, of whom 83.0% (200 of 241) achieved

SVR12. Among simeprevir-treated patients who did not meet RGT criteria, 40.0% (6 of 15) achieved SVR12. The RVR rate was 77.2% (200 of 259) in the simeprevir/PR group compared with 3.1% (4 of 129) treated with placebo/PR. Among simeprevir-treated patients who achieved RVR, 86.5% (173 of 200) subsequently achieved SVR12. At week 4, 5% (12 of 260) of simeprevir-treated patients had HCV-RNA level of 25 IU/mL or greater. Irrespective

of factors such as baseline see more HCV-RNA level, IL28B genotype, METAVIR score, and HCV subtype, SVR12 rates were significantly higher in the simeprevir/PR group than in the placebo/PR group (all P < .001) ( Table 3, Figure 1B). In simeprevir-treated patients with HCV genotype 1a infection, the presence of the Q80K polymorphism at check details baseline was associated with a lower SVR12 rate compared with those without this polymorphism at baseline (46.7% [14 of 30] vs 78.5% [62 of 79], respectively). However, the SVR12 rate was high among the 13 simeprevir-treated patients with baseline Q80K polymorphism who achieved RVR (76.9% vs 23.5% among patients without RVR). Only one simeprevir-treated patient with HCV genotype 1b infection had Q80K polymorphism at baseline; this patient achieved PIK3C2G SVR12. The

possible effect of baseline characteristics and early response parameters on SVR12 in the simeprevir/PR group is presented in Supplementary Table 1. The rate of on-treatment failure was 3.1% (8 of 260) for simeprevir/PR and 27.1% (36 of 133) for placebo/PR (Table 2). Five patients (1.9%) in the simeprevir/PR group and 93 patients (69.9%) in the placebo/PR group met the virologic stopping rule at week 4, which dictated stopping simeprevir/placebo only and continuing with PR. Respective proportions of patients meeting a virologic stopping rule requiring discontinuation of all treatment at weeks 12, 24, or 36 were 1.9% (5 of 260) and 11.4% (15 of 133) in the simeprevir/PR and placebo/PR groups. Viral breakthrough occurred in 2.3% (6 of 260) of simeprevir-treated patients; this rate was similar in patients infected with genotype 1a/other (2.7%) and genotype 1b (2.0%). No placebo-treated patients had viral breakthrough. Viral breakthrough occurred mainly during the first 12 weeks of treatment with simeprevir/PR, and 5 of 6 simeprevir-treated patients with viral breakthrough also met a virologic stopping rule. Among patients with undetectable HCV RNA at EOT, 18.5% (46 of 249) in the simeprevir/PR group and 48.4% (45 of 93) in the placebo/PR group had experienced viral relapse.