No correspondence between resistance mutations in the HCV-NS3 protease at baseline and early telaprevir-based triple therapy

This study aimed to examine HCV-NS3 protease variants at baseline and at 4weeks under triple therapy. To this end, we analyzed the presence of variants in HCV-NS3 protease region from peripheral blood samples of 16 patients infected with HCV-1 at baseline and at 4weeks of combined therapy with telaprevir, pegylated interferon, and ribavirin, using next-generation sequencing. Several variants with synonymous and non-synonymous amino acid substitutions were detected at both time points. Variants detected at low frequency corresponded to 74% (HCV-1a) and 35% (HCV-1b) of non-synonymous substitutions. We found nine PI-resistance associated variants (V36A, T54S, V55I, Q80K, Q80R, V107I, I132V, D168E, M175L) in HCV-NS3 of 10 patients. There was no correspondence of resistance-associated variant profile between baseline and at 4weeks. Moreover these resistance variants at baseline and short term treatment are not good predictors of outcome under triple therapy. Our study also shows a large number of others minor and major non-synonymous variants in HCV-NS3 early in telaprevir-based therapy that can be important for further drug-resistance association studies with newly developed PI agents.
Source: BBA Clinical - Category: Biochemistry Source Type: research