Naturally occurring dominant resistance mutations to hepatitis C virus protease and polymerase inhibitors in treatment-naïve patients.

Unlabelled: Resistance mutations to hepatitis C virus (HCV) nonstructural protein 3 (NS3) protease inhibitors in <1% of the viral quasispecies may still allow >1000-fold viral load reductions upon treatment, consistent with their reported reduced replicative fitness in vitro. Recently, however, an R155K protease mutation was reported as the dominant quasispecies in a treatment-naïve individual, raising concerns about possible full drug resistance. To investigate the prevalence of dominant resistance mutations against specifically targeted antiviral therapy for HCV (STAT-C) in the population, we analyzed HCV genome sequences from 507 treatment-naïve patients infected with HCV genotype 1 from the United States, Germany, and Switzerland.

Hepatitis C hypervariable region 1: association of reduced selection pressure in african americans with treatment failure.

In a prospective therapeutic trial, features of the hepatitis C quasispecies were investigated as possible markers of therapeutic response. Individuals chronically infected with hepatitis C genotype 1 received antiviral therapy consisting of alpha-interferon plus ribavirin. The study targeted the most rapidly evolving segment of the viral genome, hypervariable region 1 within the envelope-2 gene.