Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs

The increasing use of the integrase strand transfer inhibitor (INSTI) class for the treatment of HIV-infection has pointed to the importance of analyzing the features of HIV-1 subtypes for an improved understanding of viral genetic variability in the occurrence of drug resistance (DR). In this study...

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Main Authors: Alina Kirichenko, Ilya Lapovok, Pavel Baryshev, David A. M. C. van de Vijver, Jeroen J. A. van Kampen, Charles A. B. Boucher, Dimitrios Paraskevis, Dmitry Kireev
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/12/8/838
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author Alina Kirichenko
Ilya Lapovok
Pavel Baryshev
David A. M. C. van de Vijver
Jeroen J. A. van Kampen
Charles A. B. Boucher
Dimitrios Paraskevis
Dmitry Kireev
author_facet Alina Kirichenko
Ilya Lapovok
Pavel Baryshev
David A. M. C. van de Vijver
Jeroen J. A. van Kampen
Charles A. B. Boucher
Dimitrios Paraskevis
Dmitry Kireev
author_sort Alina Kirichenko
collection DOAJ
description The increasing use of the integrase strand transfer inhibitor (INSTI) class for the treatment of HIV-infection has pointed to the importance of analyzing the features of HIV-1 subtypes for an improved understanding of viral genetic variability in the occurrence of drug resistance (DR). In this study, we have described the prevalence of INSTI DR in a Russian cohort and the genetic features of HIV-1 integrase sub-subtype A6. We included 408 HIV infected patients who were not exposed to INSTI. Drug resistance mutations (DRMs) were detected among 1.3% of ART-naïve patients and among 2.7% of INSTI-naïve patients. The prevalence of 12 polymorphic mutations was significantly different between sub-subtypes A6 and A1. Analysis of the genetic barriers determined two positions in which subtype A (A1 and A6) showed a higher genetic barrier (G140C and V151I) compared with subtype B, and one position in which subtypes A1 and B displayed a higher genetic barrier (L74M and L74I) than sub-subtype A6. Additionally, we confirmed that the L74I mutation was selected at the early stage of the epidemic and subsequently spread as a founder effect in Russia. Our data have added to the overall understanding of the genetic features of sub-subtype A6 in the context of drug resistance.
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spelling doaj.art-b16e5b5e1a8946f5ab8dc3bb0a5ecf8c2023-11-20T08:40:36ZengMDPI AGViruses1999-49152020-07-0112883810.3390/v12080838Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIsAlina Kirichenko0Ilya Lapovok1Pavel Baryshev2David A. M. C. van de Vijver3Jeroen J. A. van Kampen4Charles A. B. Boucher5Dimitrios Paraskevis6Dmitry Kireev7Central Research Institute of Epidemiology, 111123 Moscow, RussiaCentral Research Institute of Epidemiology, 111123 Moscow, RussiaCentral Research Institute of Epidemiology, 111123 Moscow, RussiaViroscience Department, Erasmus Medical Centre, 3015 CE Rotterdam, The NetherlandsViroscience Department, Erasmus Medical Centre, 3015 CE Rotterdam, The NetherlandsViroscience Department, Erasmus Medical Centre, 3015 CE Rotterdam, The NetherlandsDepartment of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 11527 Goudi, Athens, GreeceCentral Research Institute of Epidemiology, 111123 Moscow, RussiaThe increasing use of the integrase strand transfer inhibitor (INSTI) class for the treatment of HIV-infection has pointed to the importance of analyzing the features of HIV-1 subtypes for an improved understanding of viral genetic variability in the occurrence of drug resistance (DR). In this study, we have described the prevalence of INSTI DR in a Russian cohort and the genetic features of HIV-1 integrase sub-subtype A6. We included 408 HIV infected patients who were not exposed to INSTI. Drug resistance mutations (DRMs) were detected among 1.3% of ART-naïve patients and among 2.7% of INSTI-naïve patients. The prevalence of 12 polymorphic mutations was significantly different between sub-subtypes A6 and A1. Analysis of the genetic barriers determined two positions in which subtype A (A1 and A6) showed a higher genetic barrier (G140C and V151I) compared with subtype B, and one position in which subtypes A1 and B displayed a higher genetic barrier (L74M and L74I) than sub-subtype A6. Additionally, we confirmed that the L74I mutation was selected at the early stage of the epidemic and subsequently spread as a founder effect in Russia. Our data have added to the overall understanding of the genetic features of sub-subtype A6 in the context of drug resistance.https://www.mdpi.com/1999-4915/12/8/838HIV-1A6integraseINSTIL74Ipolymorphisms
spellingShingle Alina Kirichenko
Ilya Lapovok
Pavel Baryshev
David A. M. C. van de Vijver
Jeroen J. A. van Kampen
Charles A. B. Boucher
Dimitrios Paraskevis
Dmitry Kireev
Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs
Viruses
HIV-1
A6
integrase
INSTI
L74I
polymorphisms
title Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs
title_full Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs
title_fullStr Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs
title_full_unstemmed Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs
title_short Genetic Features of HIV-1 Integrase Sub-Subtype A6 Predominant in Russia and Predicted Susceptibility to INSTIs
title_sort genetic features of hiv 1 integrase sub subtype a6 predominant in russia and predicted susceptibility to instis
topic HIV-1
A6
integrase
INSTI
L74I
polymorphisms
url https://www.mdpi.com/1999-4915/12/8/838
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