Low level of HIV-1C integrase strand transfer inhibitor resistance mutations among recently diagnosed ART-naive Ethiopians
Abstract 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 sti...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-33850-4 |
| _version_ | 1797841076386529280 |
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| author | Mulugeta Kiros Dessalegn Abeje Tefera Henok Andualem Alene Geteneh Abebech Tesfaye Tamirayehu Seyoum Woldemichael Eleni Kidane Dawit Hailu Alemayehu Melanie Maier Adane Mihret Woldaregay Erku Abegaz Andargachew Mulu |
| author_facet | Mulugeta Kiros Dessalegn Abeje Tefera Henok Andualem Alene Geteneh Abebech Tesfaye Tamirayehu Seyoum Woldemichael Eleni Kidane Dawit Hailu Alemayehu Melanie Maier Adane Mihret Woldaregay Erku Abegaz Andargachew Mulu |
| author_sort | Mulugeta Kiros |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-09T16:25:11Z |
| format | Article |
| id | doaj.art-6cf7fff221ac44a3b28050c9e21188da |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T16:25:11Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-6cf7fff221ac44a3b28050c9e21188da2023-04-23T11:15:38ZengNature PortfolioScientific Reports2045-23222023-04-011311810.1038/s41598-023-33850-4Low level of HIV-1C integrase strand transfer inhibitor resistance mutations among recently diagnosed ART-naive EthiopiansMulugeta Kiros0Dessalegn Abeje Tefera1Henok Andualem2Alene Geteneh3Abebech Tesfaye4Tamirayehu Seyoum Woldemichael5Eleni Kidane6Dawit Hailu Alemayehu7Melanie Maier8Adane Mihret9Woldaregay Erku Abegaz10Andargachew Mulu11Department of Medical Laboratory Science, College of Medicine and Health Sciences, Aksum UniversityArmauer Hansen Research InstituteDepartment of Medical Laboratory Science, College of Medicine and Health Sciences, Debre Tabor UniversityDepartment of Medical Laboratory Science, College of Health Sciences, Woldia UniversityArmauer Hansen Research InstituteArmauer Hansen Research InstituteThe Ethiopian Public Health InstituteArmauer Hansen Research InstituteDepartment Virology, Institute Medical Microbiology and Virology, Leipzig UniversityArmauer Hansen Research InstituteDepartment of Microbiology, Parasitology, and Immunology, School of Medicine, Addis Ababa UniversityArmauer Hansen Research InstituteAbstract 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.https://doi.org/10.1038/s41598-023-33850-4 |
| spellingShingle | Mulugeta Kiros Dessalegn Abeje Tefera Henok Andualem Alene Geteneh Abebech Tesfaye Tamirayehu Seyoum Woldemichael Eleni Kidane Dawit Hailu Alemayehu Melanie Maier Adane Mihret Woldaregay Erku Abegaz Andargachew Mulu Low level of HIV-1C integrase strand transfer inhibitor resistance mutations among recently diagnosed ART-naive Ethiopians Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-023-33850-4 |
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