Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia
Abstract Background The development of pretreatment drug resistance (PDR) is becoming an obstacle to the success of antiretroviral therapy (ART). Besides, data from developing settings including Ethiopia is still limited. Therefore, this study was aimed to assess HIV-1 genetic diversity and PDR muta...
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| Format: | Article |
| Language: | English |
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BMC
2020-09-01
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| Series: | Retrovirology |
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| Online Access: | http://link.springer.com/article/10.1186/s12977-020-00542-0 |
| _version_ | 1818485871733637120 |
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| author | Mulugeta Kiros Dawit Hailu Alemayehu Eleni Geberekidan Adane Mihret Melanie Maier Woldaregay Erku Abegaz Andargachew Mulu |
| author_facet | Mulugeta Kiros Dawit Hailu Alemayehu Eleni Geberekidan Adane Mihret Melanie Maier Woldaregay Erku Abegaz Andargachew Mulu |
| author_sort | Mulugeta Kiros |
| collection | DOAJ |
| description | Abstract Background The development of pretreatment drug resistance (PDR) is becoming an obstacle to the success of antiretroviral therapy (ART). Besides, data from developing settings including Ethiopia is still limited. Therefore, this study was aimed to assess HIV-1 genetic diversity and PDR mutations among ART-naive recently diagnosed HIV-1 infected individuals in Addis Ababa, Ethiopia. Methods Institutional based cross-sectional study was conducted from June to December 2018 in Addis Ababa among ART-naive recently diagnosed individuals. Partial HIV-1 pol region covering the entire protease (PR) and partial reverse transcriptase (RT) regions of 51 samples were amplified and sequenced using an in-house assay. Drug resistance mutations were examined using calibrated population resistance (CPR) tool version 6.0 from the Stanford HIV drug resistance database and the International Antiviral Society-USA (IAS-USA) 2019 mutation list. Results According to both algorithms used, 9.8% (5/51) of analyzed samples had at least one PDR Mutation. PDR mutations to Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) were the most frequently detected (7.8% and 9.8%, according to the CPR tool and IAS-USA algorithm, respectively). The most frequently observed NNRTIs-associated mutations common to both algorithms were K103N (2%), Y188L (2%), K101E (2%), and V106A (2%), while E138A (2%) was observed according to IAS-USA only. Y115F and M184V (mutations that confer resistance to NRTIs) dual mutations were detected according to both criteria in a single study participant (2%). PDR mutation to protease inhibitors was found to be low (only G73S; 2% according to the CPR tool). Phylogenetic analysis showed that 98% (50/51) of the study participants were infected with HIV-1C virus while one individual (2%) was infected with HIV-1A1 virus. Conclusions This study showed an increased level of PDR and persistence HIV-1C clade homogeneity after 15 years of the rollout of ART and 3 decades of HIV-1C circulation in Ethiopia, respectively. Therefore, we recommend routine baseline genotypic drug resistance testing for all newly diagnosed HIV infected patients before initiating treatment. This will aid the selection of appropriate therapy in achieving the 90% of patients having an undetectable viral load in consonance with the UN target. |
| first_indexed | 2024-12-10T16:14:50Z |
| format | Article |
| id | doaj.art-98e079b48baa40839e667ad177aad93d |
| institution | Directory Open Access Journal |
| issn | 1742-4690 |
| language | English |
| last_indexed | 2024-12-10T16:14:50Z |
| publishDate | 2020-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Retrovirology |
| spelling | doaj.art-98e079b48baa40839e667ad177aad93d2022-12-22T01:41:59ZengBMCRetrovirology1742-46902020-09-0117111010.1186/s12977-020-00542-0Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in EthiopiaMulugeta Kiros0Dawit Hailu Alemayehu1Eleni Geberekidan2Adane Mihret3Melanie Maier4Woldaregay Erku Abegaz5Andargachew Mulu6Department of Medical Laboratory Science, College of Medicine and Health Science, Debre Tabor UniversityArmauer Hansen Research InstituteThe Ethiopian Public Health InstituteArmauer Hansen Research InstituteInstitute of Virology, Leipzig UniversityDepartment of Microbiology, Parasitology, and Immunology, School of Medicine, Addis Ababa UniversityArmauer Hansen Research InstituteAbstract Background The development of pretreatment drug resistance (PDR) is becoming an obstacle to the success of antiretroviral therapy (ART). Besides, data from developing settings including Ethiopia is still limited. Therefore, this study was aimed to assess HIV-1 genetic diversity and PDR mutations among ART-naive recently diagnosed HIV-1 infected individuals in Addis Ababa, Ethiopia. Methods Institutional based cross-sectional study was conducted from June to December 2018 in Addis Ababa among ART-naive recently diagnosed individuals. Partial HIV-1 pol region covering the entire protease (PR) and partial reverse transcriptase (RT) regions of 51 samples were amplified and sequenced using an in-house assay. Drug resistance mutations were examined using calibrated population resistance (CPR) tool version 6.0 from the Stanford HIV drug resistance database and the International Antiviral Society-USA (IAS-USA) 2019 mutation list. Results According to both algorithms used, 9.8% (5/51) of analyzed samples had at least one PDR Mutation. PDR mutations to Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) were the most frequently detected (7.8% and 9.8%, according to the CPR tool and IAS-USA algorithm, respectively). The most frequently observed NNRTIs-associated mutations common to both algorithms were K103N (2%), Y188L (2%), K101E (2%), and V106A (2%), while E138A (2%) was observed according to IAS-USA only. Y115F and M184V (mutations that confer resistance to NRTIs) dual mutations were detected according to both criteria in a single study participant (2%). PDR mutation to protease inhibitors was found to be low (only G73S; 2% according to the CPR tool). Phylogenetic analysis showed that 98% (50/51) of the study participants were infected with HIV-1C virus while one individual (2%) was infected with HIV-1A1 virus. Conclusions This study showed an increased level of PDR and persistence HIV-1C clade homogeneity after 15 years of the rollout of ART and 3 decades of HIV-1C circulation in Ethiopia, respectively. Therefore, we recommend routine baseline genotypic drug resistance testing for all newly diagnosed HIV infected patients before initiating treatment. This will aid the selection of appropriate therapy in achieving the 90% of patients having an undetectable viral load in consonance with the UN target.http://link.springer.com/article/10.1186/s12977-020-00542-0HIV-1HIV-1 genetic diversityPretreatment drug resistanceHIV-1 subtypeART-naiveEthiopia |
| spellingShingle | Mulugeta Kiros Dawit Hailu Alemayehu Eleni Geberekidan Adane Mihret Melanie Maier Woldaregay Erku Abegaz Andargachew Mulu Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia Retrovirology HIV-1 HIV-1 genetic diversity Pretreatment drug resistance HIV-1 subtype ART-naive Ethiopia |
| title | Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia |
| title_full | Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia |
| title_fullStr | Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia |
| title_full_unstemmed | Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia |
| title_short | Increased HIV-1 pretreatment drug resistance with consistent clade homogeneity among ART-naive HIV-1 infected individuals in Ethiopia |
| title_sort | increased hiv 1 pretreatment drug resistance with consistent clade homogeneity among art naive hiv 1 infected individuals in ethiopia |
| topic | HIV-1 HIV-1 genetic diversity Pretreatment drug resistance HIV-1 subtype ART-naive Ethiopia |
| url | http://link.springer.com/article/10.1186/s12977-020-00542-0 |
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