Patients with HCV genotype-1 who have failed a direct-acting antiviral regimen: virological characteristics and efficacy of retreatment

BACKGROUND: This real-world clinical-setting study characterized the virological patterns in genotype-1 patients failing IFN-free regimens and evaluated the efficacy of re-treatment. METHODS: Seventy-three consecutive patients failing IFN-free regimens were enrolled (17 genotype 1a and 56 1b). At failure Sanger sequencing of NS3, NS5A and NS5B regions was performed by home-made protocols. RESULTS: In patients having failed an NS3 inhibitor, the prevalence of NS3-RASs was higher in the 10 with genotype 1a than in the 24 with genotype 1b (80% vs. 41.6%). In patients treated with an NS5A inhibitor, the prevalence of NS5A-RASs was very high in the 14 with genotype 1a and the 27 with genotype 1b (78.6% and 92.5%, respectively). In patients having failed sofosbuvir, the prevalence of NS5B-RASs was more frequently identified in the 45 with genotype 1b than in the 10 with genotype 1a (37.7% vs. 10%). The prevalence of NS5B-RASs in patients having failed dasabuvir was high in both genotypes, 66.6% in the 6 with genotype 1a and 45.5% in the 11 with genotype 1b. CONCLUSIONS: The prevalence of RASs was high in our real-world population. NS3, NS5A and NS5B sequencing seems mandatory in the choice of DAA re-treatment.