Hepacivirus C Targeted Locus (Loci)

Hepatitis C virus (HCV) variants that confer resistance to direct-acting-antiviral agents (DAA) have been detected by standard dideoxy-nucleoside sequencing in genotype (G) 1 viruses from DAA-naive patients. The proportion of G1 viruses containing low-abundance DAA-resistant mutations, defined as being present in between 0.5% and 25% of circulating virus variants, has been studied only in small numbers of patients, and the prevalence and potential impact of low-abundance DAA-resistant mutations in G1a- and G1b-infected patients are not fully known. We used ultradeep pyrosequencing (UDPS) to determine the proportion of patients infected with low-abundance DAA-resistant variants that could potentially explain the observed lower response rates among G1a patients. We assessed the prevalence of DAA-resistant mutations in 191 NS3 and 116 NS5B isolates from 208 DAA-naive G1-infected patients.