Background: The first direct acting antivirals (DAAs) have been recently approved in Israel, and new DAAs are being evaluated. Though resistance mutations have been identified, the impact of naturally occurring baseline mutations on treatment success is questionable.
Methods: HCV sequences were assessed in 61 HCV genotype 1carriers prior to receiving DDA treatment which included either anti HCV NS3/4A protease (Telaprevir, Boceprevir MK-5172 or ABT-450); anti NS5A (Daclatasvir, MK-8742 or ABT-267) or ABT-333 targeting the NS5B polymerase. Baseline HCV sequences of NS3/4A (n=51), NS5A (n=19) and NS5B (n=16) were interpreted using Geno2Pheno tool. In cases of breakthrough or relapse, sequencing was repeated with a new sample.
Results: Geno2Pheno identified the following baseline amino acid substitutions possibly associated with resistance: 117H (8/51, 15.6%) and 54A (1/51, 1.9%) in the NS3/4A protease. 30R (18/19, 94.7%), 31M (3/19, 15.8%), 30Q, 58A and 58S (each 1/19, 5.0%) and 93H (5/19, 26.3%) in the NS5A. No baseline NS5B mutations were found. Most patients have responded well to the various treatments and 24 weeks SVR has already been obtained in 23 (37.7%) of them. In one of two patients which relapsed following anti NS3/4A+NS5A treatment, NS5A 30R and 31M mutations were found at baseline, and an additional 93H NS5A mutation was identified following the relapse. Breakthrough occurred in one case following invico containing treatment with 54H NS3 mutation identified only after virological failure.
Conclusions: Though most baseline mutations identified herein did not affect treatment outcome, the relevance and impact of baseline resistance mutations for successful HCV combination treatment should be further assessed in a larger cohort.
