microbeПроблемы особо опасных инфекцийProblems of Particularly Dangerous Infections0370-10692658-719XRussian Research Anti-Plague Institute “Microbe”10.21055/0370-1069-2020-3-97-105microbe-1369Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESПервичные мутации лекарственной устойчивости вируса гепатита C у пациентов с впервые выявленной ВИЧ-инфекциейPrimary HCV Drug Resistance Mutations in Patients with Newly Diagnosed HIV Infectionhttps://orcid.org/0000-0003-2270-8897ОстанковаЮ. В.OstankovaYu. V.

Российская Федерация, 197101, Санкт-Петербург, ул. Мира, 14

14, Mira St., Saint Petersburg, 197101, Russian Federation

shenna1@yandex.ruhttps://orcid.org/0000-0002-0931-102XВалутитеД. Э.ValutiteD. E.

Российская Федерация, 197101, Санкт-Петербург, ул. Мира, 14

14, Mira St., Saint Petersburg, 197101, Russian Federation

pasteur@pasteurorg.ruhttps://orcid.org/0000-0002-0579-110XЗуеваЕ. Б.ZuevaE. B.

Российская Федерация, 197101, Санкт-Петербург, ул. Мира, 14

14, Mira St., Saint Petersburg, 197101, Russian Federation

pasteur@pasteurorg.ruhttps://orcid.org/0000-0002-0547-3945СериковаЕ. Н.SerikovaE. N.

Российская Федерация, 197101, Санкт-Петербург, ул. Мира, 14

14, Mira St., Saint Petersburg, 197101, Russian Federation

pasteur@pasteurorg.ruhttps://orcid.org/0000-0002-3139-3674ЩемелевА. Н.ShchemelevA. N.

Российская Федерация, 197101, Санкт-Петербург, ул. Мира, 14

14, Mira St., Saint Petersburg, 197101, Russian Federation

pasteur@pasteurorg.ruBoumbalyS.BoumbalyS.

Гвинейская Республика, Киндия;

Гвинейская Республика, Нзерекаре

 Kindia, Republic of Guinea

Nzerekare, Republic of Guinea

drboumbaly@yahoo.frBaldeT. A.L.BaldeT. A.L.

Гвинейская Республика, Киндия

Kindia, Republic of Guinea

thiernoamadoulabe.balde@gmail.comhttps://orcid.org/0000-0003-3223-8219СеменовА. В.SemenovA. V.

Российская Федерация, 197101, Санкт-Петербург, ул. Мира, 14

14, Mira St., Saint Petersburg, 197101, Russian Federation

pasteur@pasteurorg.ruФБУН «Санкт-Петербургский научно-исследовательский институт эпидемиологии и микробиологии им. Пастера»РоссияSaint-Petersburg Pasteur Research Institute of Epidemiology and MicrobiologyRussian FederationНаучно-исследовательский институт прикладной биологии Гвинеи; Международный исследовательский центр по тропическим инфекциям в ГвинееГвинеяResearch Institute of Applied Biology; Centre International de Recherche sur les Infections Tropicales en Guinée/International Research Center on Tropical Infections in the Republic of GuineaGuineaНаучно-исследовательский институт прикладной биологии ГвинеиГвинеяResearch Institute of Applied BiologyGuineaФБУН «Санкт-Петербургский научно-исследовательский институт эпидемиологии и микробиологии им. Пастера»; ГБОУ ВПО «Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова»; ГБОУ ВПО «Северо-Западный государственный медицинский университет им. И.И. Мечникова»РоссияSaint-Petersburg Pasteur Research Institute of Epidemiology and Microbiology; Saint-Petersburg State Medical University n.a. acad. I. P. Pavlov; North-Western State Medical University n.a. I. I. MechnikovRussian Federation2020191020200397105Copyright © Останкова Ю.В., Валутите Д.Э., Зуева Е.Б., Серикова Е.Н., Щемелев А.Н., Boumbaly S., Balde T.A., Семенов А.В., 20202020Останкова Ю.В., Валутите Д.Э., Зуева Е.Б., Серикова Е.Н., Щемелев А.Н., Boumbaly S., Balde T.A., Семенов А.В.Ostankova Y.V., Valutite D.E., Zueva E.B., Serikova E.N., Shchemelev A.N., Boumbaly S., Balde T.A., Semenov A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.microbe.ru/jour/article/view/1369Цель

Цель. Оценка распространенности первичных мутаций лекарственной устойчивости ВГС в гене NS5b у пациентов с впервые выявленной инфекцией ВИЧ.

Материалы и методы

Материалы и методы. Материалом исследования служили 196 бразцов плазмы крови пациентов, проживающих на территории СЗ ФО, с впервые выявленным ВИЧ.  Образцы обследовали на наличие антител анти-HCV и РНК ВГС . В случае выявления РНК ВГС осуществляли амплификацию с использованием трех пар праймеров, совместно  фланкирующих ген NS5b. После секвенирования нуклеотидной последовательности указанного гена определяли субтип вируса и выявляли мутации лекарственной устойчивости.

Результаты и обсуждение

Результаты и обсуждение. Антитела к ВГС выявлены у 18,87 % ВИЧ -инфицированных лиц, РНК ВГС – у 18,36 % пациентов, включая 89,18 % анти-ВГС  -позитивных и 1,88 % анти-ВГС -негативных больных. Показано, что ко-инфекция чаще встречается у мужчин (77,8 %), чем у женщин (22,2 %). Выявлено отличие по вирусной нагрузке ВИЧ между группами с моноинфекцией ВИЧ и с ко-инфекцией ВИЧ + ВГС , показано достоверное отличие групп по количеству CD4+ лифоцитов. При филогенетическом анализе субтипы ВГС распределены следующим образом: ВГС 1b – 47,2 %, ВГС 3а – 30,6 %, ВГС 1а – 13,9 %, ВГС 2а – 5,5 % и единственный образец определен как ВГС 2k – 2,8 %. В девяти образцах (25 %) обнаружены мутации NS5b в положениях, связанных с развитием лекарственной устойчивости ВГС , в том числе по два образца среди ВГС генотипов 1а и 3а, а также пять образцов среди ВГС 1b. Мутации среди ВГС 1а представляли собой замены C316Y и N444D, среди ВГС 1b выявлены замены C316N, C451S, S556N/G. У пациентов с ВГС 3а выявлены два образца с мутацией D310N, ассоциированной с неблагоприятным прогнозом заболевания. Полученные  данные рационально использовать для оценки динамики распространенности первичной фармакорезистентности ВГС среди ВИЧ -инфицированных лиц. 

Objective of our work was to assess prevalence of the primary HCV drug resistance mutations in the NS5b gene in patients with newly diagnosed HIV infection.

Materials and methods

Materials and methods. The study material was 196 blood plasma samples from patients living in the North-Western Federal District with newly diagnosed HIV. Samples were examined for the anti-HCV antibodies and HCV RNA presence. If HCV RNA was detected, amplification was performed using three primers pairs that co-flanked the NS5b gene. After sequencing the indicated gene nucleotide sequence, the virus subtype was determined and drug resistance mutations were detected.

Results and discussion

Results and discussion. Antibodies to HCV were detected in 18.87 % of HIV-infected individuals. HCV RNA was detected in 18.36 % of the patients, including 89.18 % anti-HCV-positive and 1.88 % anti-HCV-negative. It was shown that co-infection is more common in men (77.8 %) compared to women (22.2 %) – χ2 = 3.996 at p = 0.0456, df = 2. The difference in the HIV viral load between the groups with HIV monoinfection and with HIV + HCV coinfection was demonstrated (χ2 = 6.284 at p = 0.0432, df = 2). A significant difference between the groups by the CD4 + lyphocytes number was shown. In the phylogenetic analysis, the HCV subtypes are distributed as follows: HCV 1b – 47.2 %, HCV 3a – 30.6 %, HCV 1a – 13.9 %, HCV 2a – 5.5 % and only one sample was defined as HCV 2k – 2.8 %, respectively. Nine samples (25 %) presented NS5b mutations in  the positions related to the development of drug resistance of HCV, including two samples among HCV genotypes 1a and 3a (i.e., 5.6 % of the total HIV + HCV group), as well as five samples among HCV 1b (13.9 % of the total group). Mutations among HCV 1a were C316Y and N444D substitutions. Among HCV 1b, C316N, C451S, S556N/G substitutions were identified. Among patients with HCV 3a, 2 samples (5.6 %) with a D310N mutation associated with an unfavorable disease prognosis were found. The introduction of direct sequencing of HCV nucleotide sequences into the routine laboratory diagnostics will allow us to estimate the primary drug resistance mutations prevalence in risk groups to predict the HCV life-threatening complications development – fibrosis, cirrhosis, hepatocellular carcinoma, as well as the outcome of antiviral therapy prognosis. The data obtained can be rationally used to assess the dynamics of the HCV primary pharmacoresistance prevalence among HIV-infected individuals.

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The authors declare that there are no conflicts of interest present.