Dynamic changes of HCV genomes under selective pressure from DAAs therapy in relapsed patients

Currently, direct-acting antiviral drugs (DAAs) are widely used as therapeutic methods for hepatitis C virus (HCV)-positive patients, however, patients may experience treatment failure, and the dynamic changes of HCV genomes in these patients are unknown. In this study, three real-world DAAs cohorts were enrolled to observe clinical efficacy. In addition, serum samples from treatment failure patients at baseline and relapse were used to analyze changes of the HCV genomes at near full-length genome level, including resistance-associated variants (RAVs), viral quasispecies diversity and selection analysis. Next-generation sequencing was used as the detection method. The overall sustained virological response at 12 w after the end of treatment was achieved in 91.9% (57/62) of HCV patients, and 3 paired samples obtained from relapsed patients. All the 3 patients harbored baseline NS5A RAVs, the frequency of NS5A RAVs increased in 2 patients and a new NS5A RAV emerged in 1 patient at relapse, and almost all the viral strains existed with NS5A RAVs at relapse. The results of the viral quasispecies diversity analysis revealed that viral quasispecies diversity decreased at relapse compared to baseline, and the results of selection analysis indicated that the virus population experienced a bottleneck phenomenon, recent selective sweep and population expansion or was under purification selection after DAAs treatment. This study indicated that the clinical efficacy was excellent in real-world DAAs cohorts, and the viral strains existed at relapse were selective by DAAs therapy.