Problems of VirologyProblems of VirologyВопросы вирусологии0507-40882411-2097Central Research Institute for Epidemiology12265ArticlesСтатьиResearch ArticleA problem of the HIV drug resistanceПроблема резистентности вируса иммунодефицита человека к антиретровирусным препаратам15082014594VOL 59, NO4 (2014)ТОМ 59, №4 (2014)5909062023Copyright ©; 2014, Nossik M.N.Copyright ©; 2014, Носик М.Н.2014Nossik M.N.Носик М.Н.https://creativecommons.org/licenses/by/4.0https://virusjour.crie.ru/jour/article/view/12265

The wide use of the highly active antiretroviral therapy (HAART) of HIV infection leads to the HIV drug resistance. The simultaneous formation of the resistance to different groups of antiviral drugs compromises the efficacy of HAART. Thus, the problem of the drug resistance becomes of an enormous significance. In this review, a definition of the resistance is given; the problem of the drug-resistant strains transmission is discussed; the assays used for resistance testing are described; recommendations for the antiviral drug-resistance testing are given.

Широкое использование антиретровирусной (АРВ) терапии вируса иммунодефицита человека (ВИЧ) приводит к формированию у ВИЧ-инфицированных резистентности к лекарственным препаратам. При развитии резистентности к препаратам сразу нескольких групп возможности АРВ-терапии значительно сокращаются. Таким образом, проблема лекарственной устойчивости приобретает все большее значение. в обзоре дается понятие термина «резистентность», освещается проблема передачи резистентных вариантов ВИЧ, описываются существующие в настоящее время методы определения резистентности и показания к проверке на лекарственную резистентность.

human immunodeficiency virusantiretroviral therapyantiviral drug-resistanceвирус иммунодефицита человекаантиретровирусная терапиялекарственная резистентностьCoovadia A., Hunt G., Abrams E.J. et al. Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitorbased therapy. Clin. Infect. Dis. 2009; 48: 462-72.Hauser A., Mugenyi K., Kabasiguzi R. et al. Emergence and persistence of minor drug-resistant HIV-1 variants in Ugandan women after nevirapine single-dose prophylaxis. PLoS One. 2011; 6 (5). Available at: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0020357 (Accessed 16 September 2013).Alteri C., Svicher V., Gori C. et al. Characterization of the patterns of drug-resistance mutations in newly diagnosed HIV-1 infected patients naive to the antiretroviral drugs. BMC Infect. Dis. 2009; 9: 111. doi: 10.1186/1471-2334-9-111.Hrazic M., Pellegrin I., Deveaue C. et al. Genotypic drug resistance during HIV-1-primary infection in France (1996-1999): frequency and response to treatment. AIDS. 2002; 16: 793-6.Lapadula G., Izzo I., Gargiulo F. et al. Updated prevalence of genotypic resistance among HIV-1 positive patients naive to antiretroviral therapy: a single center analysis. J. Med. Virol. 2008; 80: 747-53.Little S., Holte S., Routy J. et al. Antiretroviral-drug resistance among patients recently infected with HIV. N. Engl. J. Med. 2002; 347: 385-94.Hirsch M.S., Gunthard H.F., Schapiro J.M. et al. Antiretroviral drug resistance testing in adult HIV-1 infection: 2008 recommendations of an international AIDS society-USA panel. Clin. Infect. Dis. 2008; 47: 266-85.Shafer R.W., Rhee S.Y., Bennett D.E. Consensus resistance mutations for epidemiological surveillance: basic principles and potential controversies. Antivir. Ther. 2008; 13: 59-68.Rhee S.Y., Taylor J., Fessel W.J. et al. HIV-1 protease mutations and protease inhibitor cross-resistance. Antimicrob. Agents Chemother. 2010; 54 (10): 4253-61.Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. Developed by the HHS panel on antiretroviral guidelines for adults and adolescents - a Working Group of the OARAC. 2011: 1-167.Coffin J. HIV population dynamics in vivo implications for genetic variation, pathogenesis and therapy. Science. 1995; 267: 483-9.Rayner M., Cordova B., Jackson D. Population dynamics studies of wild-type and drug-resistant mutant HIV in mixed infections. Virology. 1997; 236: 85-94.Yerli S., von Wyl V., Lederberger B. et al. Transmission of HIV-1 drug resistance in Switzerland: a 10-year molecular epidemiology survey. AIDS. 2007; 21: 2223-9.Erice A., Mayers D.L., Strike D.G. et al. Brief report: primary infection with zidovudin-resistant human immunodeficiency virus type 1. N. Engl. J. Med 1993; 328: 1163 -5.De Ronde A., Schuurman R., Goudsmit J. et al. First case of a new infection with zidovudine-resistant HIV-1 among prospectively studied intravenous drug users and homosexual men in Amsterdam, the Netherlands. AIDS. 1996; 10: 231-2.Siergrist C., Yerly S., Kaiser L. et al. Mother-to-child transmission of zidovudine-resistant HIV-1. Lancet. 1994; 344: 1771-2.Turner D., Brenner B., Moisi D. et al. Diminished representation of HIV-1 variants containing select drug resistance-conferring mutations in primary HIV-1 infection. J. Acquir. Immune Defic. Syndr. 2004; 37: 1627-31.Bloor S., Kemp S., Herzogs K. et al. Patterns of HIV drug resistance in routine clinical practice: a survey of almost 12000 samples from the USA in 1999. Antivir. Ther. 2000; 5 (Suppl. 3): 132.Pereira A., Kashuba A., Fiscus S. et al. Nucleoside analogs achieve high concentrations in seminal plasma: relationship between drug concentration and virus burden. J. Infect. Dis. 1999; 180: 2039-43.Pereira A., Smeaton L., Gerber J. et al. The pharmokinetics of amprenavir, zidovudine and lamivudine in the genital tracts of men infected with HIV-1 (AIDS clinical trials group study 850). J. Infect. Dis. 2002; 186: 198-204.Taylor S., van Heeswijk R., Hoetelmans R. et al. Concentrations of nevirapine, lamivudine and stavudine in semen of HIV-1-infected men. AIDS. 2000; 14: 1979-84.Ghosn J., Viard J.P., Katlama C. et al. Evidence of genotypic resistance diversity of archived and circulating viral strains in blood and semen of pre-treated HIV-infected men. AIDS. 2004; 18: 447-57.Choudhury B., Pillay D., Taylor S.P. Analysis of HIV-1 variation in blood and semen during treatment and treatment interruption. J. Med. Virol. 2002; 68: 467-72.Sedaghat A.R., Siliciano R.F., Wilke C.O. Low-level HIV-1 replication and the dynamics of the resting CD4+T cell reservoir for HIV-1 in the setting of HAART. BMC Infect. Dis. 2008; 8. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2254415/ (Accessed 16 September 2013).Kozal M., Amico K., Chiarella J. et al. Antiretroviral resistance and high-risk transmission behavior among HIV-positive patients in clinical care. AIDS. 2004; 18: 2185-9.Sethi A., Celentano D., Gange S. et al. High-risk behavior and potential transmission of drug-resistant HIV among injection drug users. J. Acquir. Immune Defic. Syndr. 2004; 35: 503-10.Long E., Martin H., Kreiss J. et al. Gender differences in HIV-1 diversity at time of infection. Nat. Med. 2000; 6: 71-5.Sagar M., Kirktgaard E., Long E. et al. Human immunodeficiency Virus type 1 (HIV-1) diversity at time of infection is not restricted to certain risk groups or specific HIV-1 subtypes. J. Virol. 2004; 78: 7279-83.Mayes B., Schrooten Y., Snoeck J. et al. Performance of ViroSeq HIV-1 genotyping system in routine practice at a Belgium clinical laboratory. J. Virol. Meth. 2004; 119: 45-9.Определение чувствительности вируса иммунодефицита человека к лекарственным препаратам: Методические рекомендации №5956-РХот06.08.2007.М.:Минздравсоцразвития РФ; 2007.Beerenwinkel N., Daumer M., Oette M. et al. Geno2pheno: estimating phenotypic drug resistance from HIV-1 genotypes. Nucl. Acids Res. 2003; 31: 3850-5.Mazzotta F., Lo Caputo S., Torti C. et al. Reazl versus virtual phenotype to guide treatment in heavily pretreated patients: 48-week follow-up of the Genotipo-Fenotipo di resistenza (GenPheRex) trial. J. Acquir. Immune Defic. Syndr. 2003; 32: 268-80.Palmer S., Kearny M., Maldarelli F. et al. Multiple, linked human immunodeficiency virus type 1 drug resistance mutations in treatment-experienced patients are missed by standard genotype analysis. J. Clin. Microbiol. 2005; 43: 406-13.Simen B.B., Huppler-Hullsiek K. Novak R.M. et al. Prevalence of low abundant drug resistant variants by ultra-deep sequencing in chronically HIV-infected antiretroviral naive patients and the impact on virologic outcomes. Antivir. Ther. 2007; 12: S149.Soriano V., Ledesma E., Spanish Drug Resistance Panel. Second Spanish consensus on the use of drug resistance testing in clinical practice. AIDS Rev. 2000; 2: 111-8.Bennett D.E., Bertagnolio S., Sutherland D., Gilks C.F. The World Health Organization’s global strategy for prevention and assessment of HIV drug resistance. Antivir. Ther. 2008; 13 (Suppl. 2): 1-13.О проведении надзора за циркуляцией генетических вариантов вируса иммунодефецита человека, включая циркуляцию штаммов, резистентных к антиретровирусным препаратам: Методические рекомендации № 5958-РХ от 06.08.2007. М.: Минздравсоцразвития РФ; 2007.Ладная Н.Н., Круглова А.И., Богословская Е.В. и др. Отчет о проведении порогового исследования по резистентности к АРВ препаратам в г. Москве и Московской области. Проект «Развитие стратегии лечения населения Российской Федерации, уязвимого к ВИЧ/СПИД и туберкулезу», финансируемый Глобальным фондом по борьбе со СПИДом, туберкулезом и малярией. М.; 2006.Рахманова А.Г., Петрова Л.В., Яковлев А.А. и др. Результаты определения резистентности ВИЧ к антиретровирусным препаратам у ВИЧ-инфицированных больных по материалам ГИБ №30 им. С.П. Боткина. В кн.: Материалы II конференции по вопросам ВИЧ/СПИД в Восточной Европе и Центральной Азии (ЕЕСААС 2008):2008, май 3-5, Москва. М.; 2008: 90.Nosik M., Ryzhov K., Kravtchenko A. et al. Genotypic analyses of HIV in antiretroviral drug-naive patients from Moscow and Moscow Region, Russia: In: Proceedings of 6th IAS conference on HIV pathogenesis, treatment and prevention. 2011, July 17-20, Rome, Italy: CDA002.Казеннова Е.В., Антонова О.В., Кузин С.Н. и др. Молекулярно-эпидемиологическое исследование распространения ВИЧ-1 на территории Республики Саха (Якутия). Вопросы вирусологии. 2011; 5: 30-4.