However, the addition of telaprevir/boceprevir to PegIFN/RBV has led to an increase in adverse events.[26-29] Boceprevir and telaprevir were studied in five phase 3 clinical buy PFT�� trials in both treatment-naïve and treatment-experienced patients. These trials have been extensively reviewed, so we will limit our discussion to a brief overview and focus on the implications for use of RGT. Triple-therapy using boceprevir was studied in the SPRINT-2 trial, which enrolled treatment-naïve patients with chronic, genotype 1 HCV infection.[26] This trial employed a 4-week lead-in period of PegIFN/RBV, after which treatments diverged into three

groups. Group 1 received placebo plus PegIFN/RBV; group 2 (response-guided arm) received boceprevir PLX4032 nmr triple therapy for 24 weeks, at which time all treatment was discontinued in those who had undetectable HCV RNA at clinic visits between week 8 and week 24 (not including week 24) and those with detectable HCV RNA continued treatment with PegIFN/RBV plus placebo to complete 48 weeks of therapy; and group 3 that received boceprevir plus PegIFN for a total of 44 weeks (after a 4-week lead in) even if virus levels were undetectable between weeks 8 and 24. Patients in any group who had detectable HCV RNA at week 24 were discontinued according to rules of futility.[26] Forty-four percent of patients in the boceprevir response-guided arm were eligible to stop therapy

at week 28 based on undetectable HCV RNA levels between weeks 8 and 24. Similarly, 44% of patients in the 48-week triple therapy arm had undetectable HCV RNA between weeks 8 and 24 but continued therapy to full 48-week duration as per the study protocol; HCV RNA levels were undetectable in only 12% of patients in the control arm between weeks 8 and 24. Ninety-six percent of patients in each boceprevir treatment selleck chemicals arm who achieved undetectable HCV RNA between weeks 8 and 24 also achieved SVR (group 2: 156/162; group 3: 155/161).[26] The SPRINT-2 trial had a 4-week

lead-in of PegIFN/RBV, and 5% of patients achieved RVR (undetectable HCV RNA after 4 weeks of PegIFN/RBV) during that time. Previous guidelines recommended that these patients could be considered for a shortened duration of PegIFN/RBV therapy if baseline factors supported such a decision.[4] With the addition of a DAA and the application of different RGT criteria, more patients are eligible for shortened duration of therapy with triple therapy (44%) than would have been eligible with PegIFN/RBV alone (12%).[26] The RESPOND-2 trial studied boceprevir-containing triple therapy among chronically infected, genotype 1 HCV-infected patients who had prior exposure to PegIFN/RBV and were either partial responders or relapsers (prior null responders were not included in the trial).[29] The RESPOND-2 trial used a lead-in of PegIFN/RBV treatment similar to the SPRINT-2 trial.