Cell culture studies of the efficacy and barrier to resistance of sofosbuvir/velpatasvir and glecaprevir/pibrentasvir against hepatitis C virus genotypes 2a, 2b and 2c.

Cell culture studies of the efficacy and barrier to resistance of sofosbuvir/velpatasvir and glecaprevir/pibrentasvir against hepatitis C virus genotypes 2a, 2b and 2c. Antimicrob Agents Chemother. 2019 Dec 09;: Authors: Ramirez S, Fernandez-Antunez C, Mikkelsen LS, Pedersen J, Li YP, Bukh J Abstract Introduction of highly efficient therapies with direct-acting antivirals (DAA) for patients with chronic hepatitis C virus (HCV) infection offers exceptional opportunities to globally control this deadly disease. For achieving this ambitious goal, it is essential to prevent antiviral resistance against the most optimal first-line and retreatment DAA choices. We performed independent comparisons of the efficacy and barrier to resistance of pangenotypic DAA regimens for HCV genotype 2 infections, using previously, and newly developed efficient cell culture adapted strains of subtypes 2a, 2b and 2c. With applied experimental cell culture conditions, combination treatment with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir DAA-regimens was efficient in eradicating HCV infections, in contrast to single drug treatments frequently leading to viral escape. Sequence analysis of drug targets from recovered viruses revealed known resistance associated substitutions (RAS) emerging in the NS3 protease or NS5A after treatment failure, which were genetically stable after viral passage and exhibited significant phenotypic resistance. After sofosbuvi...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research