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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Main Authors: Mulugeta Kiros, Dawit Hailu Alemayehu, Eleni Geberekidan, Adane Mihret, Melanie Maier, Woldaregay Erku Abegaz, Andargachew Mulu
Format: Article
Language:English
Published: BMC 2020-09-01
Series:Retrovirology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12977-020-00542-0
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spelling doaj-98e079b48baa40839e667ad177aad93d2020-11-25T03:23:50ZengBMCRetrovirology1742-46902020-09-0117111010.1186/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
collection DOAJ
language English
format Article
sources DOAJ
author Mulugeta Kiros
Dawit Hailu Alemayehu
Eleni Geberekidan
Adane Mihret
Melanie Maier
Woldaregay Erku Abegaz
Andargachew Mulu
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
author_facet Mulugeta Kiros
Dawit Hailu Alemayehu
Eleni Geberekidan
Adane Mihret
Melanie Maier
Woldaregay Erku Abegaz
Andargachew Mulu
author_sort Mulugeta Kiros
title 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_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_sort increased hiv-1 pretreatment drug resistance with consistent clade homogeneity among art-naive hiv-1 infected individuals in ethiopia
publisher BMC
series Retrovirology
issn 1742-4690
publishDate 2020-09-01
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.
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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