aidsВИЧ-инфекция и иммуносупрессииHIV Infection and Immunosuppressive Disorders2077-9828Baltic Medical Education Center10.22328/2077-9828-2021-13-1-70-79aids-611Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESПервичная лекарственная устойчивость среди впервые выявленных пациентов с ВИЧ-1 в Санкт-ПетербургеPrimary HIV drug resistance among newly HIV type-1 diagnosed patients in St. PetersburgИнгабиреТ.IngabireThierry

Тьерри Ингабире — аспирант кафедры инфекционных болезней взрослых и эпидемиологии

194100, Санкт-Петербург, Литовская ул., д. 2

Thierry Ingabire — Postgraduate student Department of infectious diseases of adults and epidemiology

194100, Russian Federation, St. Petersburg, Litovskaya, st. 2

ingabire@mail.ruСеменовА. В.SemenovA. V.

Семенов Александр Владимирович — доктор биологических наук, заместитель директора по инновациям, заведующий лабораторией иммунологии и вирусология ВИЧ-инфекции; доцент кафедры клинической лабораторной диагностики

197101, Санкт-Петербург, ул. Мира, д. 14

195067, Санкт-Петербург, Пискаревский пр., 47

Semenov Alexander Vladimirovich — Doctor of Biological Sciences, Deputy Director for Innovation, head of the Laboratory of Immunology and virology of HIV infection; Associate Professor at the Department of Clinical Laboratory Diagnostics

197101, St. Petersburg, st. Mira, 14

195067, Russia, St. Petersburg, Piskarevsky pr., 47

 

ЕсауленкоЕ. В.EsaulenkoE. V.

Эсауленко Елена Владимировна — доктор медицинских наук профессор, заведующая кафедрой инфекционных болезней взрослых и эпидемиологии; заведующая лабораторией вирусных гепатитов

194100, Санкт-Петербург, ул. Литовская ул., д. 2

197101, г. Санкт-Петербург, ул. Мира, 14

Esaulenko Elena Vladimirovna — Doctor of Medical Sciences, Professor, Head of the department of infectious diseases of adults and epidemiology; Head of the laboratory of viral hepatitis

194100, Russian Federation, St. Petersburg, Litovskaya st. 2

197101, St. Petersburg, st. Mira, 14

ЗуеваЕ. В.ZuevaE. B.

Зуева Елена Викторовна — кандидат биологических наук старший научный сотрудник лаборатории молекулярной иммунологии

197101, Санкт-Петербург, ул. Мира, д. 14

Zueva Elena Viktorovna — сandidate of biological sciences senior researcher, laboratory of molecular immunology

197101, St. Petersburg, st. Mira, 14

ЩемелевА. Н.SchemelevA. N.

Щемелев Александр Николаевич — младший научный сотрудник лаборатории иммунологии и вирусология ВИЧ-инфекции

197101, Санкт-Петербург, ул. Мира, 14

Schemelev Alexander Nikolaevich — junior researcher laboratory of immunology and virology of HIV infection

197101, St. Petersburg, st. Mira, 14

БушмановаА. Д.BushmanovaA. D.

Бушманова Анастасия Дмитриевна — кандидат медицинских наук, ассистент кафедры инфекционных болезней взрослых и эпидемиологии; врач-инфекционист отделения профилактики и диагностики вирусных гепатитов

194100, Санкт-Петербург, Литовская ул., д. 2

197101, Санкт-Петербург, ул. Мира, д. 14

Bushmanova Anastasia Dmitrievna — сandidate of Medical Sciences, assistant of the department of infectious diseases of adults and epidemiology; Infectious disease physician department of prevention and diagnosis of viral hepatitis

194100, Russian Federation, St. Petersburg, Litovskaya st. 2

197101, St. Petersburg, st. Mira, 14

Научно-исследовательский институт эпидемиологии и микробиологии имени Пастера; Первый Санкт-Петербургский государственный медицинский университетРоссияSt. Petersburg Pasteur Institute; Department of infectious diseases of adults and epidemiology, St. Petersburg State Pediatric Medical UniversityRussian FederationНаучно-исследовательский институт эпидемиологии и микробиологии имени Пастера; Северо-Западный государственный медицинский университет имени И. И. МечниковаРоссияSt. Petersburg Pasteur Institute; North-Western State Medical University named after I. I. MechnikovRussian FederationНаучно-исследовательский институт эпидемиологии и микробиологии имени ПастераРоссияSt. Petersburg Pasteur InstituteRussian FederationНаучно-исследовательский институт эпидемиологии и микробиологии имени Пастера; Первый Санкт-Петербургский государственный медицинский университетРоссияSt. Petersburg Pasteur InstituteRussian Federation2021270420211317079Copyright © Ингабире Т., Семенов А.В., Есауленко Е.В., Зуева Е.В., Щемелев А.Н., Бушманова А.Д., 20212021Ингабире Т., Семенов А.В., Есауленко Е.В., Зуева Е.В., Щемелев А.Н., Бушманова А.Д.Ingabire T., Semenov A.V., Esaulenko E.V., Zueva E.B., Schemelev A.N., Bushmanova A.D.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://hiv.bmoc-spb.ru/jour/article/view/611

У специалистов есть опасения, что широкое использование антиретровирусных препаратов для лечения инфекции, вызванной вирусом иммунодефицита человека 1 (ВИЧ-1), может привести к возникновению передачи лекарственно- устойчивого вируса среди лиц, впервые инфицированных ВИЧ-1. Россия — одна из растущего числа стран, где лекарственно-устойчивый ВИЧ становится серьезной проблемой для здоровья, поскольку он может снизить эффективность антиретровирусной терапии на уровне населения.

Материалы и методы

Материалы и методы. Проведен генетический анализ гена pol, полученного из плазмы ВИЧ-1, среди впервые выявленных пациентов с ВИЧ-1, не получавших антиретровирусную терапию, в период с ноября 2018 г. по октябрь 2019 г. в СПБ ГБУЗ «Клинической инфекционной больнице им. С. П. Боткина». Использовали полимеразную цепную реакцию с обратной транскриптазой (ОТ-ПЦР) с последующим прямым секвенированием продуктов ПЦР для определения распространенности мутаций, вызывающих первичную лекарственную устойчивость. Генотипы ВИЧ-1 определяли филогенетическим анализом.

Результаты

Результаты. Преобладающим подтипом ВИЧ-1 был A1 (87,2%), далее за ним следовали B (11,8%) и CRF06_cpx (1%). Общая распространенность первичной лекарственной устойчивости составляла 11%. Вирус с известными мутациями, придающими устойчивость к любым ингибиторам нуклеозидной обратной транскриптазы (НИОТ), был обнаружен у 8 человек, к любым не-НИОТ — у 5 пациентов и к любым ингибиторам протеаз — в одном случае. Вирус с множественной лекарственной устойчивостью выявлен у 2 человек (2%).

Заключение

Заключение. Распространение генотипов ВИЧ-1 в Санкт-Петербурге (Россия) разнообразно. Растущая распространенность первичной лекарственной устойчивости у пациентов, ранее не получавших антиретровирусную терапию, демонстрирует важность постоянного мониторинга из-за проблем, которые возникают при дальнейшем лечении.

There is concern that the widespread use of antiretroviral drugs (ARV) to treat human immunodeficiency virus 1 (HIV-1) infection may result in the emergence of transmission of drug-resistant virus among persons newly infected with HIV-1. Russia is one of a growing number of countries in the world where drug-resistant HIV is becoming a serious health problem because it has the potential to compromise the efficacy of antiretroviral therapy (ART) at the population level.

Materials and methods

Materials and methods. We performed a genetic analysis of the HIV-1 plasma derived pol gene among the newly diagnosed ART-naïve HIV-1 infected patients during the period from November 2018 to October 2019 in the St. Petersburg Clinical Infectious Diseases Hospital named after S.P. Botkin. We used reverse transcriptase polymerase chain reaction (RT-PCR) followed by direct sequencing of PCR products to determine the prevalence of primary drug resistance (PDR) conferring mutations. HIV-1 genotypes were determined by phylogenetic analysis.

Results

Results. The predominant HIV-1 subtype was A1 (87.2%), followed by B (11.8%) and CRF06_cpx (1%). The overall prevalence of PDR was 11%. Virus with known resistance-conferring mutations to any nucleoside reverse transcriptase inhibitors (NRTIs) was found in 8 individuals, to any non NRTIs in 5 subjects, and to any protease inhibitors in 1 case. Multidrug-resistant virus was identified in 2 individuals (2%).

Conclusion

Conclusion. The distribution of HIV-1 genotypes in St. Petersburg, Russia is diverse. The emerging prevalence of PDR in ART-naïve patients demonstrates the significance of constant monitoring due to the challenges it presents towards treatment.

ВИЧ-1лекарственная устойчивостьмутацииантиретровирусная терапиялекарственная устойчивость ВИЧ-1HIV-1drug resistancemutationsantiretroviral therapyHIV-1 drug resistanceReferencesUNAIDS (2018). UNAIDS data 2018. State of the epidemic in Eastern Europe and Central Asia. Р. 273–278.UNAIDS (2018). UNAIDS data 2018. State of the epidemic in Eastern Europe and Central Asia. Р. 273–278.Beyrer C., Wirtz A.L., O’Hara G., Léon N., Kazatchkine M. The expanding epidemic of HIV-1 in the Russian Federation // PLOS Medicine. 2017. Vol. 14 (11). e1002462. https://doi.org/10.1371/journal.pmed.1002462.Beyrer C., Wirtz A.L., O’Hara G., Léon N., Kazatchkine M. The expanding epidemic of HIV-1 in the Russian Federation // PLOS Medicine. 2017. Vol. 14 (11). e1002462. https://doi.org/10.1371/journal.pmed.1002462.Clark F. World Report: Gaps remain in Russia’s response to HIV/AIDS // The Lancet. 2016. Vol. 388 (10047). Р. 857–858. https://doi.org/10.1016/S0140-6736(16)31480-5.Clark F. World Report: Gaps remain in Russia’s response to HIV/AIDS // The Lancet. 2016. Vol. 388 (10047). Р. 857–858. https://doi.org/10.1016/S0140-6736(16)31480-5.Belyakov N.A., Rassokhin V.V., Semenov A.V., Konovalova N.V., Ogurtsova S.V., Svetlichnaya Yu.S., Boeva E.V., Bobreshova A.S., Esaulenko E.V., Sukhoruk A.A. HIV infection and comorbidal conditions in the northwestern federal district of the Russian Federation in 2016 // Аnalytical review. St. Petersburg, 2017.Belyakov N.A., Rassokhin V.V., Semenov A.V., Konovalova N.V., Ogurtsova S.V., Svetlichnaya Yu.S., Boeva E.V., Bobreshova A.S., Esaulenko E.V., Sukhoruk A.A. HIV infection and comorbidal conditions in the northwestern federal district of the Russian Federation in 2016 // Аnalytical review. St. Petersburg, 2017.UNAIDS. Global HIV & AIDS statistics 2020. Р. 1–7.UNAIDS. Global HIV & AIDS statistics 2020. Р. 1–7.UNAIDS 90–90–90, an ambitious treatment target to help end the AIDS epidemic. 2017. Р. 1–40.UNAIDS 90–90–90, an ambitious treatment target to help end the AIDS epidemic. 2017. Р. 1–40.Phillips A.N., Stover J., Cambiano V., Nakagawa F., Jordan M.R., Pillay D. et al. Impact of HIV drug resistance on HIV/AIDS associated mortality, new infections and antiretroviral therapy program costs in sub-Saharan Africa // Journal of Infectious Diseases. 2017. Vol. 215 (9). Р. 1362–1365.Phillips A.N., Stover J., Cambiano V., Nakagawa F., Jordan M.R., Pillay D. et al. Impact of HIV drug resistance on HIV/AIDS associated mortality, new infections and antiretroviral therapy program costs in sub-Saharan Africa // Journal of Infectious Diseases. 2017. Vol. 215 (9). Р. 1362–1365.WHO (2017). Guidelines on the public health response to pretreatment HIV drug resistance. Р. 1–84.WHO (2017). Guidelines on the public health response to pretreatment HIV drug resistance. Р. 1–84.Hofstra L.M. High rates of transmission of drug-resistant HIV in Aruba resulting in reduced susceptibility to the WHO recommended first-line regimen in nearly half of newly diagnosed HIV-infected patients // Clinical Infectious Diseases. 2017. Vol. 64. Р. 1092–1097.Hofstra L.M. High rates of transmission of drug-resistant HIV in Aruba resulting in reduced susceptibility to the WHO recommended first-line regimen in nearly half of newly diagnosed HIV-infected patients // Clinical Infectious Diseases. 2017. Vol. 64. Р. 1092–1097.Sanchez Rivas E., Nijhuis M., Bank L.E.A., Wilkinson E, Kelly K., Boden D., Hurley A., Zhang L. et al. HIV-1 drug resistance in newly infected individuals // The Journal of the American Medical Association. 1999. Vol. 282 (12). Р. 1135–1141.Sanchez Rivas E., Nijhuis M., Bank L.E.A., Wilkinson E, Kelly K., Boden D., Hurley A., Zhang L. et al. HIV-1 drug resistance in newly infected individuals // The Journal of the American Medical Association. 1999. Vol. 282 (12). Р. 1135–1141.Chauhan C.K., Lakshmi P.V.M., Sagar V., Sharma A., Arora S.K., Kumar R. Primary HIV Drug Resistance among Recently Infected Cases of HIV in North-West India // AIDS Research and Treatment. 2019. 8 p.Chauhan C.K., Lakshmi P.V.M., Sagar V., Sharma A., Arora S.K., Kumar R. Primary HIV Drug Resistance among Recently Infected Cases of HIV in North-West India // AIDS Research and Treatment. 2019. 8 p.Lebedeva N.N., Zverev S.Y., Kulagin V.V., Kurina N.V., Pronin A.Yu., Mikova O.E., Milovanova I.I., Polovitsa N.V., Sandyreva T.P., Sizova N.V., Sklyar L.F., Tertyshnaya Yu. N., Belkina N.S., Shemshura A.B., Bobkova M.R. HIV drug resistance early warning indicators and their assessment in some regions of Russia // HIV Infection and Immunosuppressive Disorders. 2018. Vol. 10 (4). Р. 67–75.Lebedeva N.N., Zverev S.Y., Kulagin V.V., Kurina N.V., Pronin A.Yu., Mikova O.E., Milovanova I.I., Polovitsa N.V., Sandyreva T.P., Sizova N.V., Sklyar L.F., Tertyshnaya Yu. N., Belkina N.S., Shemshura A.B., Bobkova M.R. HIV drug resistance early warning indicators and their assessment in some regions of Russia // HIV Infection and Immunosuppressive Disorders. 2018. Vol. 10 (4). Р. 67–75.Struck D., Lawyer G., Ternes A.M., Schmit J.C., Bercoff D.P. COMET: adaptive context-based modeling for ultrafast HIV-1 subtype identification // Nucleic Acids Research. 2014. Vol. 42. Р. 144.Struck D., Lawyer G., Ternes A.M., Schmit J.C., Bercoff D.P. COMET: adaptive context-based modeling for ultrafast HIV-1 subtype identification // Nucleic Acids Research. 2014. Vol. 42. Р. 144.Pineda-Pena A.C., Faria N.R., Imbrechts S., Libin P., Abecasis A.B., Deforche K. et al. Automated subtyping of HIV-1 genetic sequences for clinical and surveillance purposes: performance evaluation of the new REGA version 3 and seven other tools // Infection, Genetics and Evolution. 2013. Vol. 19. Р. 337–348.Pineda-Pena A.C., Faria N.R., Imbrechts S., Libin P., Abecasis A.B., Deforche K. et al. Automated subtyping of HIV-1 genetic sequences for clinical and surveillance purposes: performance evaluation of the new REGA version 3 and seven other tools // Infection, Genetics and Evolution. 2013. Vol. 19. Р. 337–348.WHO (2016). Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Recommendations for a public health approach. 2nd ed. Clinical guidelines HIV diagnosis, 2016. Р. 1–34.WHO (2016). Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Recommendations for a public health approach. 2nd ed. Clinical guidelines HIV diagnosis, 2016. Р. 1–34.Maldonado J. The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug- Resistant Mutations // Viruses. 2018. Vol. 10 (7). Р. 376.Maldonado J. The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug- Resistant Mutations // Viruses. 2018. Vol. 10 (7). Р. 376.Hylton E., Wirtz A.L., Zelaya C.E, Latkin C., Peryshkina A., Mogilnyi V. et al. Sexual Identity, Stigma, and Depression: the Role of the «Antigay Propaganda Law» in Mental Health among Men Who Have Sex with Men in Moscow, Russia // Journal of Urban Health. 2017. Vol. 94 (3). Р. 319–329.Hylton E., Wirtz A.L., Zelaya C.E, Latkin C., Peryshkina A., Mogilnyi V. et al. Sexual Identity, Stigma, and Depression: the Role of the «Antigay Propaganda Law» in Mental Health among Men Who Have Sex with Men in Moscow, Russia // Journal of Urban Health. 2017. Vol. 94 (3). Р. 319–329.Wirtz A.L., Zelaya C.E., Peryshkina A., Latkin C., Mogilnyi V., Galai N. et al. Social and structural risks for HIV among migrant and immigrant men who have sex with men in Moscow, Russia: Implications for prevention // AIDS Care. 2014. Vol. 26 (3). Р. 387–395.Wirtz A.L., Zelaya C.E., Peryshkina A., Latkin C., Mogilnyi V., Galai N. et al. Social and structural risks for HIV among migrant and immigrant men who have sex with men in Moscow, Russia: Implications for prevention // AIDS Care. 2014. Vol. 26 (3). Р. 387–395.Deniz G., Cristiana O., Serhat U., Josip B The growing HIV epidemic in Central Europe: a neglected issue? // Journal of Virus Eradication. 2016. Vol. 2 (3). Р. 156–161.Deniz G., Cristiana O., Serhat U., Josip B The growing HIV epidemic in Central Europe: a neglected issue? // Journal of Virus Eradication. 2016. Vol. 2 (3). Р. 156–161.Peltzer K. Correlates of HIV infection among people visiting public HIV counseling and testing clinics in Mpumalanga, South Africa // African Health Sciences. 2012. Vol. 12. Р. 8–16.Peltzer K. Correlates of HIV infection among people visiting public HIV counseling and testing clinics in Mpumalanga, South Africa // African Health Sciences. 2012. Vol. 12. Р. 8–16.Zenin P.V., Pronin A., Serkov I.L., Khametova K.M., Orlova-Morozova E.A., Giliazova A.V. et al. Molecular epidemiology of HIV-1 strains in the Moscow Region // Problems of Virology. 2010. Vol. 55. Р. 25–29.Zenin P.V., Pronin A., Serkov I.L., Khametova K.M., Orlova-Morozova E.A., Giliazova A.V. et al. Molecular epidemiology of HIV-1 strains in the Moscow Region // Problems of Virology. 2010. Vol. 55. Р. 25–29.Vinogradova A., Delgado E., Rakhmanova A., Yakovlev A., Cuevas M. T., Nájera R Thomson M. M. Molecular Epidemiology of HIV-1 in St. Petersburg, Russia: Predominance of Subtype A, Former Soviet Union Variant, and Identification of Intrasubtype Subclusters // Journal of Acquired Immune Deficiency Syndromes. 2009. Vol. 51 (3). Р. 332–339.Vinogradova A., Delgado E., Rakhmanova A., Yakovlev A., Cuevas M. T., Nájera R Thomson M. M. Molecular Epidemiology of HIV-1 in St. Petersburg, Russia: Predominance of Subtype A, Former Soviet Union Variant, and Identification of Intrasubtype Subclusters // Journal of Acquired Immune Deficiency Syndromes. 2009. Vol. 51 (3). Р. 332–339.Lebedev A., Мoskaleychik F., Pronin A., Kazennova E., Bobkova M. Human Immunodeficiency Virus-1 Diversity in the Moscow Region, Russia: Phylodynamics of the Most Common Subtypes // Frontiers in Microbiology. 2019. Vol. 10. doi: 10.3389/fmicb.2019.00320.Lebedev A., Мoskaleychik F., Pronin A., Kazennova E., Bobkova M. Human Immunodeficiency Virus-1 Diversity in the Moscow Region, Russia: Phylodynamics of the Most Common Subtypes // Frontiers in Microbiology. 2019. Vol. 10. doi: 10.3389/fmicb.2019.00320.Bbosa N., Kaleebu P., Ssemwanga D. HIV subtype diversity worldwide // Current Opinion in HIV and AIDS. 2019. Vol. 14 (3). Р. 153–160.Bbosa N., Kaleebu P., Ssemwanga D. HIV subtype diversity worldwide // Current Opinion in HIV and AIDS. 2019. Vol. 14 (3). Р. 153–160.Buchacz K., Young B., Palella F. J., Armon C., Brooks J. T… Trends in use of genotypic resistance testing and frequency of major drug resistance among antiretroviral-naive persons in the HIV Outpatient Study, 1999–2011 // Journal of Antimicrobial Chemotherapy. 2015. Vol. 70 (8). Р. 2337–2346.Buchacz K., Young B., Palella F. J., Armon C., Brooks J. T… Trends in use of genotypic resistance testing and frequency of major drug resistance among antiretroviral-naive persons in the HIV Outpatient Study, 1999–2011 // Journal of Antimicrobial Chemotherapy. 2015. Vol. 70 (8). Р. 2337–2346.Hofstra L.M. et al. Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe // Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2016. Vol. 62. Р. 655–663.Hofstra L.M. et al. Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe // Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2016. Vol. 62. Р. 655–663.Zhao S., Feng Y., Hu J. et al. Prevalence of Transmitted HIV drug resistance in antiretroviral treatment naïve newly diagnosed individuals in China // Scientific Reports. 2018. Vol. 8. Р. 12273.Zhao S., Feng Y., Hu J. et al. Prevalence of Transmitted HIV drug resistance in antiretroviral treatment naïve newly diagnosed individuals in China // Scientific Reports. 2018. Vol. 8. Р. 12273.Pace C.A., Lioznov D., Cheng D.M., Wakeman S.E., Raj A., Walley A.Y., Samet J.H. Sexually transmitted infections among HIV-infected heavy drinkers in St Petersburg, Russia. International // Journal of STD & AIDS. 2012. Vol. 23 (12). Р. 853–858.Pace C.A., Lioznov D., Cheng D.M., Wakeman S.E., Raj A., Walley A.Y., Samet J.H. Sexually transmitted infections among HIV-infected heavy drinkers in St Petersburg, Russia. International // Journal of STD & AIDS. 2012. Vol. 23 (12). Р. 853–858.Bennett D.E., Myatt M., Bertagnolio S., Sutherland D., Gilks C.F. Recommendations for surveillance of transmitted HIV drug resistance in countries scaling up antiretroviral treatment // Antiviral Therapy. 2008. Vol. 13 (2). p. 25–36.Bennett D.E., Myatt M., Bertagnolio S., Sutherland D., Gilks C.F. Recommendations for surveillance of transmitted HIV drug resistance in countries scaling up antiretroviral treatment // Antiviral Therapy. 2008. Vol. 13 (2). p. 25–36.Kirichenko A.A., Kireev D.E., Lopatukhin A.E., Murzakova A.V., Lapovok I.A., Ladnaya N.N., Pokrovsky V.V. Prevalence and structure of HIV-1 drug resistance among treatment naïve patients since the introduction of antiretroviral therapy in the Russian Federation // HIV Infection and Immunosuppressive Disorders. 2019. Vоl. 11 (2). Р. 75–83.Kirichenko A.A., Kireev D.E., Lopatukhin A.E., Murzakova A.V., Lapovok I.A., Ladnaya N.N., Pokrovsky V.V. Prevalence and structure of HIV-1 drug resistance among treatment naïve patients since the introduction of antiretroviral therapy in the Russian Federation // HIV Infection and Immunosuppressive Disorders. 2019. Vоl. 11 (2). Р. 75–83.Oroz M., Begovac J., Planinić A. et al. Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia // Scientific Reports. 2019. Vоl. 9. Р. 17307.Oroz M., Begovac J., Planinić A. et al. Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia // Scientific Reports. 2019. Vоl. 9. Р. 17307.Zaitseva N.N., Parfenova O.Yu. Analysis of spread of initial resistance of HIV to antiretroviral medicines in Privolzhsky Federal District // World of Transport and Transportation. 2016. Vоl. 14 (3). Р. 93–35.Zaitseva N.N., Parfenova O.Yu. Analysis of spread of initial resistance of HIV to antiretroviral medicines in Privolzhsky Federal District // World of Transport and Transportation. 2016. Vоl. 14 (3). Р. 93–35.

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