Characterization of primary direct-acting antiviral (DAA) drugs resistance mutations in NS5A/NS5B regions of hepatitis C virus with genotype 1a and 1b from patients with chronic hepatitis

Author(s)

Ana Paula de Torres Santos ^[1] ; Vanessa Cristina Martins Silva ^[2] ; Maria Cássia Mendes-Corrêa ^[3] ; Marcilio Figueiredo Lemos ^[4] ; Fernanda de Mello Malta ^[5] ; Rúbia Anita Ferraz Santana ^[6] ; Gregório Tadeu Fernando Dastoli ^[7] ; Vanessa Fusco Duarte de Castro ^[8] ; João Renato Rebello Pinho ; Regina Célia Moreira ^[10]

Affiliation

^[1] Universidade de São Paulo. Faculdade de Medicina. Hospital das Clínicas - Brasil

^[2] Instituto Adolfo Lutz, Centro de Virologia. Laboratório de Hepatites Virais - Brasil

^[3] Universidade de São Paulo. Faculdade de Medicina. Instituto de Medicina Tropical de São Paulo - Brasil

^[4] Instituto Adolfo Lutz, Centro de Virologia. Laboratório de Hepatites Virais - Brasil

^[5] Universidade de São Paulo. Faculdade de Medicina. Instituto de Medicina Tropical de São Paulo - Brasil

^[6] Hospital Israelita Albert Einstein - Brasil

^[7] Hospital Israelita Albert Einstein - Brasil

^[8] Hospital Israelita Albert Einstein - Brasil

^[10] Instituto Adolfo Lutz, Centro de Virologia. Laboratório de Hepatites Virais - Brasil

• Document type: Journal article
• Source: Revista do Instituto de Medicina Tropical de São Paulo; v. 64, 2022-09-30.

Abstract

ABSTRACT The Hepatitis C virus (HCV) infection is a public health problem. The high level of HCV replication and its lack of post-transcriptional correction mechanisms results in the emergence of viral variants and the difficulty in determining polymorphisms and variants that contain the substitutions associated with resistance towards new antivirals. The main focus of this study was to map the NS5A and NS5B polymorphisms and resistance mutations to new antiviral drugs in HCV strains genotype 1 from patients with chronic hepatitis C infection. Serum samples were collected from patients who underwent routine viral load tests at the Instituto Adolfo Lutz, Sao Paulo city, Brazil. A total of 698 and 853 samples were used for the characterization of NS5A and NS5B regions, respectively, which comprise the HCV genotypes 1a and 1b. The prevalence of resistance mutations found in the NS5A region was 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 analyzed drugs. These findings support that 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. (AU)

• FAPESP's process: 17/01809-9 - Characterizing HCV primary resistance mutations for direct acting antiviral drug (DAA)
• Grantee: Regina Célia Moreira
• Support Opportunities: Regular Research Grants