Identification of NS5B resistance-associated mutations in hepatitis C virus circulating in treatment-naïve Cameroonian patients.

Objectives: NS5B polymerase inhibitors are essential in the treatment of hepatitis C virus (HCV) infection. Although direct-acting antivirals (DAAs) are generally effective, their efficacy can be compromised by resistance mutations, particularly in the NS5B protein. This research aimed to identify naturally occurring mutations in the NS5B gene linked to DAA resistance in treatment-naïve Cameroonian patients with chronic hepatitis C. Methods: Whole blood samples were collected from patients with chronic hepatitis C, from which plasma was subsequently separated and stored at -80°C for molecular analysis. The NS5B gene fragments were amplified using designated primers, and nucleotide sequences were acquired via the Sanger sequencing platform. Results: Analysis of sequences revealed three genotypes: genotype 4 (38.49%), genotype 1 (38.38%), and genotype 2 (23.14%). The most prevalent subtypes were 4f (22.05%) and 1e (17.84%). The clinically significant S282T mutation, which confers high-level resistance to sofosbuvir, was detected in one patient infected with HCV genotype 1e. Similarly, the C316N substitution, associated with reduced susceptibility to non-nucleoside NS5B inhibitors, was identified in 16 patients, all belonging to genotype 1e. The Q309R mutation was detected in 19 genotype 1 sequences, and the L320F mutation was found in one genotype 4f sequence. Conclusions: Our investigation revealed that HCV patients who had not previously received DAA therapy exhibited a variety of NS5B gene alterations. Consequently, future treatment failure may be more likely due to these alterations.