HIV-1 subtype diversity, phylogenetic analysis and study of drug resistance in strains circulating in the Ural Federal District

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 opport...

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Main Authors: M. V. Piterskiy, A. G. Gusev, O. A. Khodakov, Yu. A. Zakharova, A. V. Semenov
Format: Article
Language:Russian
Published: Central Research Institute for Epidemiology 2022-03-01
Series:Журнал микробиологии, эпидемиологии и иммунобиологии
Subjects:
Online Access:https://microbiol.crie.ru/jour/article/viewFile/1177/702
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author M. V. Piterskiy
A. G. Gusev
O. A. Khodakov
Yu. A. Zakharova
A. V. Semenov
author_facet M. V. Piterskiy
A. G. Gusev
O. A. Khodakov
Yu. A. Zakharova
A. V. Semenov
author_sort M. V. Piterskiy
collection DOAJ
description 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 IIIIV 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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spelling doaj.art-c4be7472cf8a4cba93ac9b8c0b98fc6b2023-11-13T17:19:30ZrusCentral Research Institute for EpidemiologyЖурнал микробиологии, эпидемиологии и иммунобиологии0372-93112686-76132022-03-01991385310.36233/0372-9311-178789HIV-1 subtype diversity, phylogenetic analysis and study of drug resistance in strains circulating in the Ural Federal DistrictM. V. Piterskiy0https://orcid.org/0000-0001-5506-2389A. G. Gusev1https://orcid.org/0000-0002-7886-9406O. A. Khodakov2https://orcid.org/0000-0003-1493-6080Yu. A. Zakharova3https://orcid.org/0000-0003-3416-0902A. V. Semenov4https://orcid.org/0000-0003-3223-8219Yekaterinburg Research Institute of Viral Infections, State Research Center of Virology and Biotechnology “Vector”Yekaterinburg Research Institute of Viral Infections, State Research Center of Virology and Biotechnology “Vector”Yekaterinburg Research Institute of Viral Infections, State Research Center of Virology and Biotechnology “Vector”Yekaterinburg Research Institute of Viral Infections, State Research Center of Virology and Biotechnology “Vector”Yekaterinburg Research Institute of Viral Infections, State Research Center of Virology and Biotechnology “Vector”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 IIIIV 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.https://microbiol.crie.ru/jour/article/viewFile/1177/702hivsubtypegenotyperesistancedrug resistance mutationsgenetic barriers to resistance
spellingShingle M. V. Piterskiy
A. G. Gusev
O. A. Khodakov
Yu. A. Zakharova
A. V. Semenov
HIV-1 subtype diversity, phylogenetic analysis and study of drug resistance in strains circulating in the Ural Federal District
Журнал микробиологии, эпидемиологии и иммунобиологии
hiv
subtype
genotype
resistance
drug resistance mutations
genetic barriers to resistance
title HIV-1 subtype diversity, phylogenetic analysis and study of drug resistance in strains circulating in the Ural Federal District
title_full HIV-1 subtype diversity, phylogenetic analysis and study of drug resistance in strains circulating in the Ural Federal District
title_fullStr HIV-1 subtype diversity, phylogenetic analysis and study of drug resistance in strains circulating in the Ural Federal District
title_full_unstemmed HIV-1 subtype diversity, phylogenetic analysis and study of drug resistance in strains circulating in the Ural Federal District
title_short HIV-1 subtype diversity, phylogenetic analysis and study of drug resistance in strains circulating in the Ural Federal District
title_sort hiv 1 subtype diversity phylogenetic analysis and study of drug resistance in strains circulating in the ural federal district
topic hiv
subtype
genotype
resistance
drug resistance mutations
genetic barriers to resistance
url https://microbiol.crie.ru/jour/article/viewFile/1177/702
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