Prevalence of NS5B Resistance Mutations in Hepatitis C Virus (HCV) Treatment Naive South Africans

Abstract

Background: HCV NS5B is a major target for drugs that directly inhibit viral replication. Naturally occurring mutations that reduce susceptibility to NS5B inhibitors have been reported. Objectives: The present study aimed at screening treatment resistance mutations in the NS5B region in South Africa. Methods: The study comprised 42 NS5B sequences (amino acids 228 - 335), derived from treatment-naive HCV-infected patients at Dr George Mukhari Academic hospital. Nucleotide sequences were aligned, translated into amino acids, and compared to mutations associated with drug resistance described in the literature. Results: The most common mutation in this study was Q309R, which was present in all genotypes except genotype 1b. Mutation A333E was detected only in genotype 5a. The NS5B polymorphism C316N, which is associated with resistance to HCV-796, was found in 3 of 4 genotype 1b sequences. The resistance mutations D244N, S282T, C316Y, S326G, and T329I were not detected in any of the analyzed sequences. Position 309 was under positive selection in genotype 5a. Conclusions: The data indicated the presence of previously described NS5B resistance mutations in South African treatment-naive patients, suggesting that drug resistance testing would be useful prior to the initiation of antiviral therapy for HCV.