Prevalence of drug-resistance mutations to direct-acting antiviral drugs in hepatitis C virus 3a
Objective. Determination of the prevalence of drug-resistance mutations to direct-acting antiviral drugs (DAAs) in hepatitis C virus (HCV) genotype 3a.Grishaeva A.A., Chernyshova A.S., Ponezheva Zh.B., Makashova V.V., Mannanova I.V., Omarova Kh.G., Khafizov K.F., Chanyshev M.D.
Materials and methods. The study included 44 patients diagnosed with chronic hepatitis C, genotype 3a. Five patients (11.4%) had a history of DAA therapy for chronic hepatitis C without virological response. HCV RNA sequencing was performed using the HCV-seq NGS panel.
Results. Genomic sequences were obtained for all samples, and therapy resistance mutations were analyzed. The following mutation frequencies were observed in NS3: A166S/T – 20.5%; D168R – 2.3%; I170V – 11.4%; in NS5a: A30K/S/T – 9.1%; L31I – 2.3%; S62T/L – 22.7%; Y93H – 4.5%; in NS5b: K100R – 2.3%. Quasispecies were analyzed for resistance mutations in five patients with a history of unsuccessful DAA therapy. Patient 1 was found to have the A30K mutation, while quasispecies analysis revealed P32L and Y93H in 10% and 14% of reads, respectively. Patient 2 was found to have the 28M and 62L mutations and the A30S quasivariant (10%). The viral genome of patient 3 also contained the 28M and 62L mutations; quasispecies were absent. Patient 4 was found to have the A30K mutation, and patient 5 had the S62L mutation.
Conclusion. Investigation of HCV resistance mutations is advisable in patients with a history of unsuccessful therapy. Additional quasispecies analysis can identify hidden resistance mutations that can lead to treatment failure and relapse.
Keywords
hepatitis C virus
mutations
resistance
therapy
genotype 3a
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About the Authors
Antonina A. Grishaeva, Cand. Med. Sci., Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; antoninagrishaeva@yandex.ru; https://orcid.org/0000-0002-1326-9274Anastasia S. Chernyshova, Laboratory Assistant, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; asyaq01@gmail.com; https://orcid.org/0009-0000-2440-1309
Zhanna B. Ponezheva, MD, Head, Department of Clinical Infectious Pathology, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; doktorim@mail.ru; http://orcid.org/0000-0002-6539-4878
Professor Vera V. Makashova, MD, Leading Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; veramakashova@yandex.ru; https://orcid.org/0000-0002-0982-3527
Irina V. Mannanova, Cand. Med. Sci., Senior Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; irinasemenova07@rambler.ru; https://orcid.org/0000-0003-2244-8810
Khadizhat G. Omarova, Cand. Med. Sci., Head, Department of Clinical Trials, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; omarova71@inbox.ru; http://orcid.org/0000-0002-9682-2230
Kamil F. Khafizov, Cand. Biol. Sci., Head, Laboratory of Genomic Research, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; kkhafizov@gmail.com; https://orcid.org/0000-0001-5524-0296
Mikhail D. Chanyshev, Cand. Biol. Sci., Senior Researcher, Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, Moscow, Russia; chanishq@gmail.com; https://orcid.org/0000-0002-6943-2915
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