Molecular epidemiology of hepatitis C virus and resistance to direct-acting antivirals in tuberculosis patients of Western Siberia (Tomsk Region)

Background Hepatitis C virus infection and tuberculosis represent two major infectious disease burdens worldwide, with co-infection posing particular clinical challenges. The advent of direct-acting antivirals targeting hepatitis C virus (HCV) non-structural proteins NS3, NS5A, and NS5B has transformed hepatitis C treatment, achieving viral eradication in over 95% of patients. However, the emergence of resistance-associated substitutions (RAS) threatens treatment efficacy, particularly in vulnerable populations such as tuberculosis patients, who face elevated risks of drug-induced liver injury and complex drug interactions. Objective To assess the prevalence, genetic diversity, and presence of RAS in HCV isolates circulating among infected patients residing in the Tomsk Region of Russia. Materials and methods A total of 308 serum samples were collected from tuberculosis patients with confirmed HCV RNA positivity. HCV subtypes and recombinant form were determined by phylogenetic analysis of core region and NS5B region sequences which were obtained via Sanger sequencing. For a part of subtype 1b ( n = 29) and 3a ( n = 57) isolates, full-genome or targeted NS3, NS5A, and NS5B sequences were obtained via Illumina next-generation sequencing, followed by RAS analysis. Results Four HCV subtypes and one recombinant form were identified: 1b (43.5%), 3a (42.2%), 1a (12.3%), 2a (1.0%), 2k/1b (1.0%). The study yielded the following baseline RAS frequency data depending on the subtype. NS3: A166S/T (21.1%) was detected among subtype 3a isolates; Y56F (10.3%), S122G (10.3%) and V170I (13.8%) were detected among subtype 1b isolates. NS5A: A30K/S (5.3%), Q/S62L (12.3%) and Y93H (1.8%) were detected among subtype 3a isolates; among the subtype 1b isolates, R30Q (3.4%), L31M (3.4%), P58S (3.4%), and Y93H (3.4%) were detected. NS5B: among the subtype 3a isolates, A150V (40.4%) and K206E (22.8%) were detected; among the subtype 1b isolates, L159F (37.9%), C316N (48.3%), M414L (3.4%), and S556G (24.1%) were detected.