Abstract
Background. The development of direct acting antivirals (DAAs) has spurred a revolution in treatment of patients with chronic hepatitis C. However, there are cases showing no response to treatment. In 5% of cases, the viral breakthrough is most likely caused by DAA resistance mutations in the hepatitis C virus genome.The purpose of the study is to detect drug resistance mutations of hepatitis C virus in patients with DAA treatment failure.Materials and methods. The study was performed on plasma samples from 3 patients diagnosed with chronic hepatitis C virus infection and demonstrating DAA virological treatment failure. All isolates had genotype 1b. Drug resistance mutations were detected by using direct sequencing of NS3, NS5A, and NS5B genome regions. The detection technique was developed at the Pasteur Research Institute of Epidemiology and Microbiology.Results. Drug resistance mutations were detected in all cases. By using the Geno2pheno [hcv] 0.92 tool, nucleotide substitutions were detected in different viral genome regions and presumably caused resistance or decreased sensitivity to antivirals both present and absent in the sofosbuvir + daclatasvir combination therapy. Antiviral treatment failure in patients with chronic hepatitis C is caused by drug resistance mutations.Conclusions. The developed technique is efficient for detection of drug resistance mutations in NS3, NS5A, and NS5B regions in cases of virological failure of DAA treatment.
Highlights
The development of direct acting antivirals (DAAs) has spurred a revolution in treatment of patients with chronic hepatitis C
Direct-acting antiviral agents resistance-associated polymorphisms in Сhinese treatment-naïve patients infected with genotype 1b hepatitis C virus
The article was submitted 27.05.2020; accepted for publication 28.10.2020; published 25.02.2021
Summary
Валутите Д.Э.1 , Семенов А.В.1–3, Останкова Ю.В.1, Козлов К.В.4, Борисов А.Г.5, Назаров В.Д.2, Тотолян А.А.1,2. Появление препаратов прямого противовирусного действия (ПППД) стало большим достижением в лечении пациентов с хроническим гепатитом С. Цель работы — выявить мутации лекарственной устойчивости вируса гепатита С у пациентов с неэффективной терапией ПППД. Мутации лекарственной устойчивости были выявлены во всех случаях. Неэффективность терапии противовирусными препаратами у пациентов с хроническим гепатитом С обус ловлена мутациями лекарственной устойчивости. Разработанный метод позволяет выявлять мутации лекарственной устойчивости в генах NS3, NS5A, NS5B при вирусологической неэффективности терапии ПППД. Ключевые слова: вирус гепатита С, мутации лекарственной устойчивости, препараты прямого противовирусного действия. Для цитирования: Валутите Д.Э., Семенов А.В., Останкова Ю.В., Козлов К.В., Борисов А.Г., Назаров В.Д., Тотолян А.А. Выявление мутаций лекарственной устойчивости вируса гепатита С у пациентов с неэффективной терапией препаратами прямого противовирусного действия.
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