المؤلفون: Kirichenko, A. (Alina), Lapovok, I. (Ilya), Baryshev, P. (Pavel), Vijver, D.A.M.C. (David) van de, Kampen, J.J.A. (Jeroen) van, Boucher, C.A.B. (Charles), Paraskevis, D. (Dimitrios), Kireev, D. (Dmitry)

المصدر: Viruses vol. 12 no. 8

مصطلحات موضوعية: A6, founder effect, genetic barrier, HIV-1, INSTI, integrase, L74I, phylogenetics, polymorphisms, Russia

الوصف: 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.

وصف الملف: application/pdf

العلاقة: http://repub.eur.nl/pub/129477Test; urn:hdl:1765/129477

الإتاحة: https://doi.org/10.3390/v12080838Test
http://repub.eur.nl/pub/129477Test

المؤلفون: El, Bouzidi, K., Kemp, S.A., Charurat, M.E.

مصطلحات موضوعية: integrase L74I mutation, HIV Integrase Inhibitors, HIV-1, Africa, Western

الوصف: OBJECTIVES: HIV-1 integrase inhibitors are recommended as first-line therapy by WHO, though efficacy and resistance data for non-B subtypes are limited. Two recent trials have identified the integrase L74I mutation to be associated with integrase inhibitor treatment failure in HIV-1 non-B subtypes. We sought to define the prevalence of integrase resistance mutations, including L74I, in West Africa. METHODS: We studied a Nigerian cohort of recipients prior to and during receipt of second-line PI-based therapy, who were integrase inhibitor-naive. Illumina next-generation sequencing with target enrichment was used on stored plasma samples. Drug resistance was interpreted using the Stanford Resistance Database and the IAS-USA 2019 mutation lists. RESULTS: Of 115 individuals, 59.1% harboured CRF02_AG HIV-1 and 40.9% harboured subtype G HIV-1. Four participants had major IAS-USA integrase resistance-associated mutations detected at low levels (2%-5% frequency). Two had Q148K minority variants and two had R263K (one of whom also had L74I). L74I was detected in plasma samples at over 2% frequency in 40% (46/115). Twelve (26.1%) had low-level minority variants of between 2% and 20% of the viral population sampled. The remaining 34 (73.9%) had L74I present at >20% frequency. L74I was more common among those with subtype G infection (55.3%, 26/47) than those with CRF02_AG infection (29.4%, 20/68) (P?=?0.005). CONCLUSIONS: HIV-1 subtypes circulating in West Africa appear to have very low prevalence of major integrase mutations, but significant prevalence of L74I. A combination of in vitro and clinical studies is warranted to understand the potential implications. Copyright The Author(s) 2020. ; https://doi.org/10.1093/jac/dkaa033Test

العلاقة: The Journal of antimicrobial chemotherapy; https://www.scopus.com/inward/record.uri?eid=2-s2.0-85084717778&doi=10.1093%2fjac%2fdkaa033&partnerID=40&md5=277fe6b3b47b946788ca899eeb461748Test; http://hdl.handle.net/10713/12825Test

الإتاحة: https://doi.org/10.1093/jac/dkaa033Test
http://hdl.handle.net/10713/12825Test

المؤلفون: 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

المصدر: Viruses; Volume 12; Issue 8; Pages: 838

مصطلحات موضوعية: HIV-1, A6, integrase, INSTI, L74I, polymorphisms, genetic barrier, founder effect, phylogenetics, Russia

جغرافية الموضوع: agris

الوصف: 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.

وصف الملف: application/pdf

العلاقة: Animal Viruses; https://dx.doi.org/10.3390/v12080838Test

الإتاحة: https://doi.org/10.3390/v12080838Test

المؤلفون: Ilya Lapovok, Charles A. Boucher, Jeroen J. A. van Kampen, Pavel Baryshev, Kireev De, David A. M. C. van de Vijver, Alina Kirichenko, Dimitrios Paraskevis

المساهمون: Virology

المصدر: Viruses, Vol 12, Iss 838, p 838 (2020)
Viruses, 12(8):838. Multidisciplinary Digital Publishing Institute (MDPI)
Viruses
Volume 12
Issue 8

مصطلحات موضوعية: 0301 basic medicine, Adult, Male, Genotype, 030106 microbiology, lcsh:QR1-502, Context (language use), HIV Infections, Drug resistance, HIV Integrase, medicine.disease_cause, INSTI, Article, lcsh:Microbiology, Russia, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Virology, Drug Resistance, Viral, medicine, Prevalence, Humans, Genetic variability, HIV Integrase Inhibitors, genetic barrier, A6, Phylogeny, Genetics, Mutation, Polymorphism, Genetic, biology, virus diseases, Sequence Analysis, DNA, Integrase, phylogenetics, 030104 developmental biology, Infectious Diseases, founder effect, Cohort, biology.protein, Hiv 1 integrase, HIV-1, Female, integrase, L74I, polymorphisms, Founder effect

الوصف: 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-naï
ve patients and among 2.7% of INSTI-naï
ve 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.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1afb5e24fc4ff9aba35f560745b1a2edTest
https://www.mdpi.com/1999-4915/12/8/838Test

مستخلص: 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.

مصطلحات الفهرس: A6, founder effect, genetic barrier, HIV-1, INSTI, integrase, L74I, phylogenetics, polymorphisms, Russia, info:eu-repo/semantics/article

URL: http://repub.eur.nl/pub/129477Test