Журнал микробиологии, эпидемиологии и иммунобиологии. 2022; 99: 38-53
Разнообразие субтипов, филогенетический анализ и изучение лекарственной устойчивости штаммов ВИЧ-1, циркулирующих в Уральском федеральном округе
https://doi.org/10.36233/0372-9311-178Аннотация
Введение. Уральский федеральный округ (УФО) является одной из наиболее эпидемически неблагополучных территорий в Российской Федерации по ВИЧ-инфекции на протяжении последних 20 лет. Общее число лиц, живущих с ВИЧ/СПИД (ЛЖВС), получающих антиретровирусную терапию (АРТ), превышает 100 тыс. человек (61,7% от всех ЛЖВС в УФО), что создаёт предпосылки для широкого распространения резистентных штаммов.
Целью исследования явились определение субтиповой структуры ВИЧ, оценка генетической гетерогенности выделенных штаммов ВИЧ, анализ распространённости мутаций лекарственной устойчивости (МЛУ) ВИЧ к антиретровирусным препаратам (АРВП) и частоты выявления резистентности к АРВП у лиц, получающих АРТ в УФО.
Материалы и методы. Обследованы 223 пациента на 3–4-й стадии ВИЧ-инфекции, проживающие на территории УФО. Для определения субтипов и МЛУ в гене pol ВИЧ-1 проведены молекулярно-генетические исследования с применением тест-системы «АмплиСенс® HIV-Resist-Seq» методом секвенирования по Сэнгеру на анализаторе «Applied Biosystems 3500». Генетическую гетерогенность оценивали с помощью расчёта идентичности участка генома выделенных штаммов в сравнении с геномами зарубежных штаммов ВИЧ, а также с использованием филогенетического анализа.
Результаты. В изучаемой группе пациентов идентифицированы 5 субтипов ВИЧ-1: субтип A6 встречался в 91,03% случаев, субтип B — в 2,69%, на 3 рекомбинантных субтипа (CRF03_A6B, CRF02_AG, CRF63_02A6) пришлось 6,28%. Среди выделенных штаммов ВИЧ 43,9% имеют большое генетическое сходство (идентичность не менее 97%) со штаммами, выделенными от пациентов из стран ближнего зарубежья (Беларусь, Казахстан, Кыргызстан, Узбекистан, Литва); 35,9% сходны со штаммами, выделенными от пациентов из стран дальнего зарубежья (США, Китай, Южная Корея, Австралия, Швеция, Германия). Установлена высокая гетерогенность генетических вариантов штаммов ВИЧ, циркулирующих на территории УФО, что является неблагоприятным фактором для диагностики резистентности и лечения ВИЧ. Наиболее распространены МЛУ одновременно к нуклеозидным и ненуклеозидным ингибиторам обратной транскриптазы, выявленные в 81 (36,3%) образце. МЛУ M184V, формирующая резистентность к НИОТ, встречалась чаще других (p = 0,0008) и была выявлена в 88 (39,5%) образцах.
Заключение. В субтиповой структуре ВИЧ доминирующим субтипом являлся субтип A6, наиболее распространённый в странах, ранее входивших в состав СССР. Генетическая гетерогенность штаммов ВИЧ, циркулирующих в УФО, позволяет предполагать продолжающиеся заносы ВИЧ-инфекции в УФО из популяций, находящихся за пределами России. Полученные результаты подтверждают высокую распространённость МЛУ (62,8%) и лекарственной устойчивости ВИЧ-1 (60,1%) среди лиц с ВИЧ/СПИД, проживающих на территории УФО. При этом резистентность высокого уровня выявлена у 56,5% пациентов, что требует увеличения охвата лиц, живущих с ВИЧ, обследованием на резистентность ВИЧ, в том числе внедрения мониторинга за первичной резистентностью, в целях оптимизации схем АРТ первой линии.
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Journal of microbiology, epidemiology and immunobiology. 2022; 99: 38-53
HIV-1 subtype diversity, phylogenetic analysis and study of drug resistance in strains circulating in the Ural Federal District
https://doi.org/10.36233/0372-9311-178Abstract
Introduction. Ural Federal District (UFD) has been one of the most HIV-affected areas in the Russian Federation during past 20 years. The total number of people living with HIV/AIDS (PLWH) and receiving antiretroviral therapy (ART) exceeds 100,000 (61.7% of all PLWH in the UFD), which creates opportunities for the wide spread of resistant HIV strains.
Research aim was to determine the distribution of HIV-1 subtypes, evaluate the genetic heterogeneity of HIV-1 strains, and analyze the prevalence of HIV-1 drug resistance mutations (DRM) and the incidence of acquired resistance to antiretroviral drugs (ARVDs) in PLWH receiving ART in the UFD.
Materials and methods. 223 patients receiving ART at stage III–IV of HIV infection living in the UFD were examined. To determine the subtypes and the DRM in the HIV-1 pol gene, molecular genetic studies were performed using the AmpliSense® HIV-Resist-Seq kit by Sanger sequencing on the Applied Biosystems 3500 Genetic Analyzer. The genetic heterogeneity was evaluated by calculating the identity of the genome region of the isolated strains in comparison with the genomes of foreign HIV strains, as well as using phylogenetic analysis.
Results. In the studied group of patients, 5 subtypes of HIV-1 were identified: subtype A6 prevalence was 91.03%, that of subtype B was 2.69%, 3 recombinant subtypes (CRF03_A6B, CRF02_AG, CRF63_02A6) accounted for 6.28%. Among analyzed HIV-1 strains, 43.9% had a significant genetic similarity (identity of at least 97%) with the strains isolated from patients from neighboring countries (Belarus, Kazakhstan, Kyrgyzstan, Uzbekistan, Lithuania), 35.9% were similar to the strains isolated from patients from far-abroad countries (USA, China, South Korea, Australia, Sweden, Germany). A high heterogeneity of the circulating genetic variants of HIV-1 strains in the territory of the UFD region was established, which is an unfavorable factor for the diagnosis and treatment of HIV. The most common DRMs to both nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) were detected in 81 specimens (36.3%). NRTI resistance-forming M184V DRM was more common than any other DRM with statistical significance (p = 0,0008) and was detected in 88 specimens (39.5%).
Conclusion. In the subtype structure of HIV-1, the dominant subtype was subtype A6, the most common in the countries that were formerly part of the USSR. The heterogeneity of the HIV-1 strains circulating in the UFD suggests that HIV-1 infection continues to be introduced into the UFD from populations outside the Russian Federation. The findings confirm the high prevalence of DRMs (62.8%) and secondary drug resistance of HIV-1 (60.1%) among PLWH in the territory of the UFD. At the same time, high-level resistance was detected in 56.5% of patients, which requires increasing the coverage of HIV resistance testing, including the introduction of monitoring for primary resistance, in order to optimize first-line ART regimens.
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