HEPATITIS C VIRUS (NS5A) DRUG RESISTANCE MUTATIONS IN PATIENTS WITH THE HISTORY OF DIRECT-ACTING ANTIVIRAL DRUGS TREATMENT (2018–2024)
Abstract
Background. Identifying NS5A gene resistance mutations in patients with treatment failure is crucial for personalized therapy indication, making it possible to prevent repeated failures and achieve complete viral eradication. Objective. To assess the spectrum and prevalence of HCV NS5A gene drug resistance mutations in patients with virological failure of direct-acting antiviral (DAA) therapy based on the results of the 2018–2024 study. Material and methods. The study included 675 patients with virological failure after the treatment with NS5A inhibitors. HCV genotyping and resistance mutation detection were performed using Sanger sequencing of Core/E1 and NS5A genome fragments. Statistical data processing was performed using Statistica v.10. Results. HCV subtypes 3a, 1b, and 1a are predominant among patients with DAA therapy failure. Resistanceassociated mutations (RASs) were detected in 64,0% of cases. RASs were identified in 23,6% of cases for the subtype 1a, in 67,3% for the subtype 1b and in 75,9% for the subtype 3a. Overall, the RAS spectrum for the subtype 1b was broader than for the subtypes 1a and 3a. Conclusion. For the first time in the Republic of Belarus, the prevalence and profile of RAS in HCV-infected patients with DAA therapy failure were determined. HCV-3a exhibits the highest RAS prevalence compared to HCV-1a and HCV-1b. The predominance of multiple mutations requires a personalized approach to the therapy to achieve HCV
elimination.
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