The median time to loss of resistant Galunisertib molecular weight variants was 13 months overall (Table 2) (13, 15, and 9 months for prior null and partial responders, and relapsers, respectively). The median time to loss of the common genotype 1b variants (position 54 and 156; 3-4 months) was generally less than that of the common genotype 1a variants (position 36, 155, and 36+155; 13-15 months). This subanalysis of peginterferon/ribavirin treatment-experienced patients treated with the HCV protease inhibitor telaprevir in the REALIZE trial explored the effect of peginterferon/ribavirin lead-in, prior peginterferon/ribavirin treatment response,

genotype subtype, and baseline variants on treatment outcome, and further characterized the emergence of resistance in patients who did not achieve an SVR. No new telaprevir-resistant variants were detected and the pattern of resistance pathways selleck compound was consistent with

that seen in treatment-naïve patients.19 Importantly, this analysis also showed that resistant variants could no longer be detected by population sequencing in the majority of patients after a median follow-up time of 11 months. Prior to treatment in the REALIZE trial, predominant variants resistant to protease inhibitors were generally detectable by population sequencing in only a very small percentage (typically <3%) of patients, which is in agreement with other studies including those in the treatment-naïve setting.19-21 Also in line with other studies,20, 22, 23 the presence of resistant variants at baseline does not necessarily preclude successful treatment (i.e., SVR) in all patient groups,

especially in prior relapsers. However, there might have been an effect in prior null responders. Regarding the use of a 4-week peginterferon/ribavirin lead-in phase before the initiation of telaprevir, no differences in the rates of on-treatment virologic failure or relapse were observed between the concurrent and delayed initiation of telaprevir. Further, the use (or not) of a peginterferon/ribavirin Farnesyltransferase lead-in had no significant effect on the number of patients who had emergent telaprevir-resistant variants, or on the type of variants observed following virologic failure. The data from this virologic analysis are in agreement with results from the primary analysis of the REALIZE trial,4 in which SVR rates were similar between the telaprevir-based treatment arms with and without a lead-in. Therefore, our findings confirm that a peginterferon/ribavirin lead-in is not required with telaprevir. In contrast, a Phase 2 study of boceprevir previously suggested that lowering HCV RNA levels with a 4-week peginterferon/ribavirin pretreatment may reduce the emergence of protease-resistant variants, decrease viral breakthrough rates during treatment, and increase SVR rates.