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Frequency of baseline NS5A resistance-associated substitutions in patients infected with genotype 1 of hepatitis C virus in Croatia (CROSBI ID 308124)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

Simicic, Petra ; Grgic, Ivana ; Santak, Maja ; Vince, Adriana ; Lepej, Snjezana Zidovec Frequency of baseline NS5A resistance-associated substitutions in patients infected with genotype 1 of hepatitis C virus in Croatia // Microbial pathogenesis, 136 (2019), 103694, 7. doi: 10.1016/j.micpath.2019.103694

Podaci o odgovornosti

Simicic, Petra ; Grgic, Ivana ; Santak, Maja ; Vince, Adriana ; Lepej, Snjezana Zidovec

engleski

Frequency of baseline NS5A resistance-associated substitutions in patients infected with genotype 1 of hepatitis C virus in Croatia

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.

Hepatitis C virus ; Genotype 1 ; Resistance-associated substitutions ; Direct-acting antivirals ; Population-based sequencing

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Podaci o izdanju

136

2019.

103694

7

objavljeno

0882-4010

1096-1208

10.1016/j.micpath.2019.103694

Povezanost rada

Biologija, Interdisciplinarne prirodne znanosti, Kliničke medicinske znanosti, Temeljne medicinske znanosti

Poveznice
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