Patients in the T12/PR48 arm (without a lead-in) received telaprevir plus peginterferon/ribavirin for 12 weeks, followed simultaneously by placebo for 4 weeks and peginterferon/ribavirin for 36 weeks. Telaprevir was taken orally at 750 mg every 8 hours, with ribavirin MAPK inhibitor at 1,000-1,200 mg/day, and peginterferon alfa-2a administered subcutaneously

at a dose of 180 μg/week. Telaprevir was stopped in patients with HCV RNA >100 IU/mL at weeks 4, 6, and 8 after the start of telaprevir; these individuals could continue peginterferon/ribavirin. All treatment was discontinued in patients with <2 log10 HCV RNA decrease from baseline to week 12 in the T12/PR48 group Decitabine in vitro or week 16 in the lead-in T12/PR48 group, or in those with detectable HCV RNA at weeks 24 or 36. Plasma HCV RNA quantification was performed using the COBAS TaqMan assay, v. 2.0 (Roche, Switzerland). The lower limit of quantification (LLOQ) was 25 IU/mL. Results below the LLOQ were reported as “<25 IU/mL, detected,” or “<25 IU/mL, target not detected.” HCV RNA “<25 IU/mL, target not detected” is also described as undetectable HCV RNA in the study. HCV RNA levels were measured at the following study visits: screening, baseline, day 3, weeks 1, 2, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24, and 36, end of treatment (week 48 or

time of early discontinuation), and at follow-up visits 4, 12, and 24 weeks after the end of treatment. HCV RNA levels were also assessed at week 72 for all patients, including those who discontinued early. In line with the primary efficacy analysis, SVR was defined as undetectable HCV RNA 24 weeks after the last planned dose of study medication. An NS3-based genotyping method was used for genotype and subtype determination in this virologic analysis. To study HCV variants, sequencing analysis of the HCV NS3·4A regions was performed on all baseline samples. GPX6 HCV RNA was extracted from plasma virions under denaturing conditions and viral RNA was isolated on a standard commercial silica-gel

membrane using a modified QIAamp Virus BioRobot 9604 method (Qiagen, Valencia, CA). The NS3·4A protease regions were amplified using a nested reverse-transcriptase polymerase chain reaction assay. The resulting DNA was purified and sequenced; the lower limit of detection for the sequencing assay was ∼1,000 IU/mL of HCV RNA. Population sequencing can typically detect down to about 25% of the viral population. In addition to baseline samples, sequencing analyses were conducted at the time of failure in cases of on-treatment virologic failure (i.e., in patients with viral breakthrough or who met a virologic stopping rule) or relapse and in patients with detectable HCV RNA at the end of treatment.