Frequency of baseline NS5A resistance-associated substitutions in patients infected with genotype 1 of hepatitis C virus in Croatia. (November 2019)

• Record Type: Journal Article
• Authors: Simicic, Petra; Grgic, Ivana; Santak, Maja; Vince, Adriana; Lepej, Snjezana Zidovec
• Is Part Of: Microbial pathogenesis. Volume 136(2019)
• Publication Date: 2019-11
• Subjects: Hepatitis C virus -- Genotype 1 -- Resistance-associated substitutions -- Direct-acting antivirals -- Population-based sequencing; RAS resistance-associated substitution -- SVR sustained virological response -- DAA direct-acting antivirals -- EBV elbasvir -- DCV daclatasvir -- LDV ledipasvir -- OMV ombitasvir -- PBV pibrentasvir -- VPV velpatasvir; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2019.103694
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: The backbone of current treatment for chronic Hepatitis C virus (HCV) infection are direct-acting antivirals targeting viral nonstructural proteins (NS3, NS4A, NS5A, NS5B). To date, there are six NS5A inhibitors approved for treatment of chronic HCV infection. The presence of drug-associated resistance substitutions is mainly due to fast error-prone replication, showing differential frequency between genotypes and subtypes. The aim of this study was to determine the frequency of baseline resistance to NS5A protein inhibitors in patients with genotype 1 HCV in Croatia. Resistance-associated substitutions (RAS) were detected by Sanger sequencing of HCV NS5A region amplified from 84 patients followed by phylogenetic analysis and analysis with Geno2Pheno algorithm. The frequency of NS5A RAS was 14.3% and highly dependent on viral subtype. The overall frequency of NS5A RAS was higher in patients infected with HCV subtype 1b (24.2%) than in those infected with HCV subtype 1a (7.8%). Overall, three resistance-conferring mutations were detected (Q30R, M28T and Y93H) along with two mutations (M28V and L31I) that cause reduced susceptibility to NS5A inhibitors. Analysis of the sequences showed two distinct subtype 1a clades with RAS detected in 4.3% (1/23) clade I and 10.7% (3/28) clade II sequences. Only a few distinct NS5A RAS were detected suggesting a high degree of homogeneity of the viral population. High frequency of clinically relevant NS5A RAS in Croatia suggest that the analysis of frequency and patterns of resistance mutations in local populations and evaluation of their possible clinical impact could be beneficial. Highlights: The frequency of baseline NS5A RAS was 14.3% in HCV genotype 1-infected patients. The type and the frequency of RAS were highly dependent on viral subtype. The frequency of RAS was three-fold higher in patients infected with HCV subtype 1b. Only a few distinct RAS suggest a high degree of homogeneity of the viral population.