Characterization of Primary Direct Acting Antiviral Drugs (DAA) Resistance Mutations in NS5A/NS5B Regions of Hepatitis C Virus with Genotype 1a and 1b from Patients with Chronic Hepatitis

Abstract Hepatitis C virus (HCV) infection is a public health problem with an estimated 71 million infected people worldwide. The high level of HCV replication and its lack of post - transcriptional correction mechanisms result in the rapid emergence of viral variants, difficulty in determining polymorphisms, and variants that contain substitutions associated with resistance and/or reduction of susceptibility towards new antivirals. The aim of this study was to map the polymorphisms in NS5A and NS5B and resistance mutations to new antiviral drugs in HCV strains with genotype 1a and 1b derived from patients with chronic hepatitis C infection. Serum samples from patients who underwent routine viral load tests and monitoring at the laboratory of viral hepatitis at the Adolfo Lutz Institute, São Paulo, Brazil were collected. A total of 698 and 853 samples were used for the characterization of NS5A and NS5B regions respectively; comprising HCV genotypes 1a and 1b. The prevalence of resistance mutations in the NS5A region was found to be 6.4%, with Y93H, L31M, Q30R, and Y93N as the main resistance-associated substitutions (RAS). No NS5B- associated RAS was observed for any of the drugs analyzed. This study reveals the presence of significant RAS in the HCV serum samples. These findings support the RAS test should be offered to individuals with poor response to double combination regimens prior to treatment initiation, thereby assisting strain vigilance and selection of effective treatment or retreatment options using DAA regimens.