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Low level of HIV-1C integrase strand transfer inhibitor resistance mutations among recently diagnosed ART-naive Ethiopians

With the widespread use of Integrase strand transfer inhibitors (INSTIs), surveillance of HIV-1 pretreatment drug resistance is critical in optimizing antiretroviral treatment efficacy. However, despite the introduction of these drugs, data concerning their resistance mutations (RMs) is still limite...

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Autores principales: Kiros, Mulugeta, Tefera, Dessalegn Abeje, Andualem, Henok, Geteneh, Alene, Tesfaye, Abebech, Woldemichael, Tamirayehu Seyoum, Kidane, Eleni, Alemayehu, Dawit Hailu, Maier, Melanie, Mihret, Adane, Abegaz, Woldaregay Erku, Mulu, Andargachew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121640/
https://www.ncbi.nlm.nih.gov/pubmed/37085698
http://dx.doi.org/10.1038/s41598-023-33850-4
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author Kiros, Mulugeta
Tefera, Dessalegn Abeje
Andualem, Henok
Geteneh, Alene
Tesfaye, Abebech
Woldemichael, Tamirayehu Seyoum
Kidane, Eleni
Alemayehu, Dawit Hailu
Maier, Melanie
Mihret, Adane
Abegaz, Woldaregay Erku
Mulu, Andargachew
author_facet Kiros, Mulugeta
Tefera, Dessalegn Abeje
Andualem, Henok
Geteneh, Alene
Tesfaye, Abebech
Woldemichael, Tamirayehu Seyoum
Kidane, Eleni
Alemayehu, Dawit Hailu
Maier, Melanie
Mihret, Adane
Abegaz, Woldaregay Erku
Mulu, Andargachew
author_sort Kiros, Mulugeta
collection PubMed
description With the widespread use of Integrase strand transfer inhibitors (INSTIs), surveillance of HIV-1 pretreatment drug resistance is critical in optimizing antiretroviral treatment efficacy. However, despite the introduction of these drugs, data concerning their resistance mutations (RMs) is still limited in Ethiopia. Thus, this study aimed to assess INSTI RMs and polymorphisms at the gene locus coding for Integrase (IN) among viral isolates from ART-naive HIV-1 infected Ethiopian population. This was a cross-sectional study involving isolation of HIV-1 from plasma of 49 newly diagnosed drug-naive HIV-1 infected individuals in Addis-Ababa during the period between June to December 2018. The IN region covering the first 263 codons of blood samples was amplified and sequenced using an in-house assay. INSTIs RMs were examined using calibrated population resistance tool version 8.0 from Stanford HIV drug resistance database while both REGA version 3 online HIV-1 subtyping tool and the jumping profile Hidden Markov Model from GOBICS were used to examine HIV-1 genetic diversity. Among the 49 study participants, 1 (1/49; 2%) harbored a major INSTIs RM (R263K). In addition, blood specimens from 14 (14/49; 28.5%) patients had accessory mutations. Among these, the M50I accessory mutation was observed in a highest frequency (13/49; 28.3%) followed by L74I (1/49; 2%), S119R (1/49; 2%), and S230N (1/49; 2%). Concerning HIV-1 subtype distribution, all the entire study subjects were detected to harbor HIV-1C strain as per the IN gene analysis. This study showed that the level of primary HIV-1 drug resistance to INSTIs is still low in Ethiopia reflecting the cumulative natural occurrence of these mutations in the absence of selective drug pressure and supports the use of INSTIs in the country. However, continues monitoring of drug resistance should be enhanced since the virus potentially develop resistance to this drug classes as time goes by.
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spelling pubmed-101216402023-04-23 Low level of HIV-1C integrase strand transfer inhibitor resistance mutations among recently diagnosed ART-naive Ethiopians Kiros, Mulugeta Tefera, Dessalegn Abeje Andualem, Henok Geteneh, Alene Tesfaye, Abebech Woldemichael, Tamirayehu Seyoum Kidane, Eleni Alemayehu, Dawit Hailu Maier, Melanie Mihret, Adane Abegaz, Woldaregay Erku Mulu, Andargachew Sci Rep Article With the widespread use of Integrase strand transfer inhibitors (INSTIs), surveillance of HIV-1 pretreatment drug resistance is critical in optimizing antiretroviral treatment efficacy. However, despite the introduction of these drugs, data concerning their resistance mutations (RMs) is still limited in Ethiopia. Thus, this study aimed to assess INSTI RMs and polymorphisms at the gene locus coding for Integrase (IN) among viral isolates from ART-naive HIV-1 infected Ethiopian population. This was a cross-sectional study involving isolation of HIV-1 from plasma of 49 newly diagnosed drug-naive HIV-1 infected individuals in Addis-Ababa during the period between June to December 2018. The IN region covering the first 263 codons of blood samples was amplified and sequenced using an in-house assay. INSTIs RMs were examined using calibrated population resistance tool version 8.0 from Stanford HIV drug resistance database while both REGA version 3 online HIV-1 subtyping tool and the jumping profile Hidden Markov Model from GOBICS were used to examine HIV-1 genetic diversity. Among the 49 study participants, 1 (1/49; 2%) harbored a major INSTIs RM (R263K). In addition, blood specimens from 14 (14/49; 28.5%) patients had accessory mutations. Among these, the M50I accessory mutation was observed in a highest frequency (13/49; 28.3%) followed by L74I (1/49; 2%), S119R (1/49; 2%), and S230N (1/49; 2%). Concerning HIV-1 subtype distribution, all the entire study subjects were detected to harbor HIV-1C strain as per the IN gene analysis. This study showed that the level of primary HIV-1 drug resistance to INSTIs is still low in Ethiopia reflecting the cumulative natural occurrence of these mutations in the absence of selective drug pressure and supports the use of INSTIs in the country. However, continues monitoring of drug resistance should be enhanced since the virus potentially develop resistance to this drug classes as time goes by. Nature Publishing Group UK 2023-04-21 /pmc/articles/PMC10121640/ /pubmed/37085698 http://dx.doi.org/10.1038/s41598-023-33850-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kiros, Mulugeta
Tefera, Dessalegn Abeje
Andualem, Henok
Geteneh, Alene
Tesfaye, Abebech
Woldemichael, Tamirayehu Seyoum
Kidane, Eleni
Alemayehu, Dawit Hailu
Maier, Melanie
Mihret, Adane
Abegaz, Woldaregay Erku
Mulu, Andargachew
Low level of HIV-1C integrase strand transfer inhibitor resistance mutations among recently diagnosed ART-naive Ethiopians
title Low level of HIV-1C integrase strand transfer inhibitor resistance mutations among recently diagnosed ART-naive Ethiopians
title_full Low level of HIV-1C integrase strand transfer inhibitor resistance mutations among recently diagnosed ART-naive Ethiopians
title_fullStr Low level of HIV-1C integrase strand transfer inhibitor resistance mutations among recently diagnosed ART-naive Ethiopians
title_full_unstemmed Low level of HIV-1C integrase strand transfer inhibitor resistance mutations among recently diagnosed ART-naive Ethiopians
title_short Low level of HIV-1C integrase strand transfer inhibitor resistance mutations among recently diagnosed ART-naive Ethiopians
title_sort low level of hiv-1c integrase strand transfer inhibitor resistance mutations among recently diagnosed art-naive ethiopians
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121640/
https://www.ncbi.nlm.nih.gov/pubmed/37085698
http://dx.doi.org/10.1038/s41598-023-33850-4
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