Prevalence of hepatitis C virus NS5A resistance-associated substitutions in chronic infection with genotype 1: A pooled analysis based on deposited sequences in GenBank.

INTRODUCTION: Resistance-associated substitutions (RASs) in the NS5A gene of hepatitis C virus (HCV) has been studied as one of the predictors of response to NS5A inhibitor-containing regimens. This study aimed to evaluate the prevalence of pre-treatment naturally-occurring NS5A RASs in HCV isolates from patients with chronic HCV genotype 1 (HCV-1) infection retrieved from GenBank.

METHODS: In the search procedure, the studies with published HCV-1 NS5A sequence in GenBank were screened and evaluated for inclusion in the pooled analysis. The sequences of the included studies were retrieved from GenBank and evaluated for substitutions in amino acid positions24, 26, 28, 29, 30, 31, 32, 38, 58, 62, 92 and 93 of HCV NS5A including RASs and RASs conferring >100 resistance fold change (RASs >100X).

RESULTS: In the pooled analysis, 2409 isolates from patients with HCV-1 infection were included, consisting 1305 (54.2%) HCV-1a and 1104 (45.8%) HCV-1b isolates. The prevalence of NS5A RASs and RASs >100X were 16.0% (95%CI = 14.6%-17.5%) and 4.7% (95%CI = 3.9%-5.6%), respectively. The NS5A RASs were more frequently observed in HCV-1b isolates than in HCV-1a isolates (P < 0.001).

CONCLUSION: The naturally-occurring HCV NS5A RASs especially those with clinical relevance (RASs >100X) are observed in a small (4.7%) number of patients with HCV-1 infection.