Журнал микробиологии, эпидемиологии и иммунобиологии. 2021; 98: 18-27
Выявление мутаций лекарственной устойчивости вируса гепатита С у пациентов с неэффективной терапией препаратами прямого противовирусного действия
https://doi.org/10.36233/0372-9311-47Аннотация
Актуальность. Появление препаратов прямого противовирусного действия (ПППД) стало большим достижением в лечении пациентов с хроническим гепатитом С. Однако выявляются случаи отсутствия ответа на лечение. В 5% случаев наиболее вероятной причиной вирусологического прорыва являются мутации устойчивости к ПППД в геноме вируса гепатита С.
Цель работы — выявить мутации лекарственной устойчивости вируса гепатита С у пациентов с неэффективной терапией ПППД.
Материалы и методы. Материалом исследования служили образцы плазмы крови 3 пациентов с подтвержденным диагнозом хронического гепатита С с вирусологической неэффективностью терапии ПППД. Генотип всех изолятов — 1b. Применяли метод определения мутаций лекарственной устойчивости на основе прямого секвенирования генов NS3, NS5A, NS5B, разработанный в НИИЭМ им. Пастера. Результаты. Мутации лекарственной устойчивости были выявлены во всех случаях. Согласно базе данных Geno2pheno [hcv] 0.92, нуклеотидные замены были определены в разных генах вируса и, предположительно, обусловливали устойчивость или снижение чувствительности в отношении препаратов, как входящих в состав комбинированной терапии софосбувир + даклатасвир, так и отсутствующих в ней. Неэффективность терапии противовирусными препаратами у пациентов с хроническим гепатитом С обусловлена мутациями лекарственной устойчивости.
Выводы. Разработанный метод позволяет выявлять мутации лекарственной устойчивости в генах NS3, NS5A, NS5B при вирусологической неэффективности терапии ПППД.
Список литературы
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Journal of microbiology, epidemiology and immunobiology. 2021; 98: 18-27
Detection of drug resistance mutations of hepatitis C virus in patients with failure of the treatment with direct acting antivirals
https://doi.org/10.36233/0372-9311-47Abstract
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.
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