Prevalence of NS3 Mutations Inducing Resistance to Protease Inhibitors in Chronically Infected Hepatitis C Virus Genotype 4 Patients in Egypt

Abstract

Background and Objectives: Directly acting antiviral agents, like NS3 protease inhibitors, are representing the backbone for the current therapy of Hepatitis C virus infection. Given the heterogeneities in HCV genome, not all protease inhibitors will be equally effective against all HCV genotypes and subtypes. Data on HCV-4 mainly Egyptian strains are still inadequate. Here we investigated the prevalence of natural NS3 mutations and Resistance-associated substitutions (RAS) among HCV-4 Egyptian isolates. Methods: The NS5b and NS3 domains from 40 HCV Egyptian patients (20 therapy-naïve and 20 pegylated interferon-experienced patients, who failed to achieve sustained viral response) were sequenced. Results: Using NS5b nucleotide sequences, our 40 cases were genotyped as HCV-4 of which 38 (95%) were HCV-4a, and 2 (5%) were HCV-4o. NS3 amino acid sequence analysis showed that substitutions C16T and V36L were detected in all cases while D168H/E and T54A were found in only 3 and 1 cases, respectively. No difference could be detected between naïve and experienced patients in NS3 polymorphism. Conclusion: Our results confirm the high genetic diversity of NS3 in HCV-4 that could impair the use of some protease inhibitors to treat HCV-4 infections. The use of cocktail therapy for HCV-4 is indispensable.