Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia

Erdaw Tachbele,1,2 Samuel Kyobe,3 Fred Ashaba Katabazi,3 Edgar Kigozi,3 Savannah Mwesigwa,3 Moses Joloba,3 Alebachew Messele,1 Wondwossen Amogne,2 Mengistu Legesse,1 Rembert Pieper,4 Gobena Ameni1 1Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia; 2College of Hea...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Tachbele E, Kyobe S, Katabazi FA, Kigozi E, Mwesigwa S, Joloba M, Messele A, Amogne W, Legesse M, Pieper R, Ameni G
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	hiv-1 genetic diversity acquired drug resistance art experienced south omo ethiopia. Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/58cc8429429f41d986a5bd41e970d01e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:58cc8429429f41d986a5bd41e970d01e
record_format	dspace
spelling	oai:doaj.org-article:58cc8429429f41d986a5bd41e970d01e2021-11-18T19:40:25ZGenetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia1178-6973https://doaj.org/article/58cc8429429f41d986a5bd41e970d01e2021-11-01T00:00:00Zhttps://www.dovepress.com/genetic-diversity-and-acquired-drug-resistance-mutations-detected-by-d-peer-reviewed-fulltext-article-IDRhttps://doaj.org/toc/1178-6973Erdaw Tachbele,1,2 Samuel Kyobe,3 Fred Ashaba Katabazi,3 Edgar Kigozi,3 Savannah Mwesigwa,3 Moses Joloba,3 Alebachew Messele,1 Wondwossen Amogne,2 Mengistu Legesse,1 Rembert Pieper,4 Gobena Ameni1 1Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia; 2College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 3College of Health Sciences, Makerere University, Kampala, Uganda; 4Janssen Biopharma, South San Francisco, CA, USACorrespondence: Erdaw Tachbele Tel +251 911642880Email erdawt@yahoo.comPurpose: This study was conducted to investigate the drug resistance mutations and genetic diversity of HIV-1 in ART experienced patients in South Omo, Ethiopia.Patients and Methods: A cross-sectional study conducted on 253 adult patients attending ART clinics for ≥ 6 months in South Omo. Samples with VL ≥ 1000 copies/mL were considered as virological failures (VF) and their reverse transcriptase gene codons 90– 234 were sequenced using Illumina MiSeq. MinVar was used for the identification of the subtypes and drug resistance mutations. Phylogenetic tree was constructed by neighbor-joining method using the maximum likelihood model.Results: The median duration of ART was 51 months and 18.6% (47/253) of the patients exhibited VF. Of 47 viraemic patients, the genome of 41 were sequenced and subtype C was dominant (87.8%) followed by recombinant subtype BC (4.9%), M-09-CPX (4.9) and BF1 (2.4%). Of 41 genotyped subjects, 85.4% (35/41) had at least one ADR mutation. Eighty-one percent (33/41) of viraemic patients harbored NRTI resistance mutations, and 48.8% (20/41) were positive for NNRTI resistance mutations, with 43.9% dual resistance mutations. Among NRTI resistance mutations, M184V (73.2%), K219Q (63.4%) and T215 (56.1%) complex were the most mutated positions, while the most common NNRTI resistance mutations were K103N (24.4%), K101E, P225H and V108I 7.5% each. Active tuberculosis (aOR=13, 95% CI= 3.46– 29.69), immunological failure (aOR=3.61, 95% CI=1.26– 10.39), opportunistic infections (aOR=8.39, 95% CI= 1.75– 40.19), and poor adherence were significantly associated with virological failure, while rural residence (aOR 2.37; 95% CI: 1.62– 9.10, P= 0.05), immunological failures (aOR 2.37; 95% CI: 1.62– 9.10, P= 0.05) and high viral load (aOR 16; 95% CI: 5.35 51.59, P < 0.001) were predictors of ADR mutation among the ART experienced and viraemic study subjects.Conclusion: The study revealed considerable prevalence of VF and ADR mutation with the associated risk indicators. Regular virological monitoring and drug resistance genotyping methods should be implemented for better ART treatment outcomes of the nation.Keywords: HIV-1, genetic diversity, acquired drug resistance, ART experienced, South Omo, EthiopiaTachbele EKyobe SKatabazi FAKigozi EMwesigwa SJoloba MMessele AAmogne WLegesse MPieper RAmeni GDove Medical Pressarticlehiv-1genetic diversityacquired drug resistanceart experiencedsouth omoethiopia.Infectious and parasitic diseasesRC109-216ENInfection and Drug Resistance, Vol Volume 14, Pp 4833-4847 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hiv-1 genetic diversity acquired drug resistance art experienced south omo ethiopia. Infectious and parasitic diseases RC109-216
spellingShingle	hiv-1 genetic diversity acquired drug resistance art experienced south omo ethiopia. Infectious and parasitic diseases RC109-216 Tachbele E Kyobe S Katabazi FA Kigozi E Mwesigwa S Joloba M Messele A Amogne W Legesse M Pieper R Ameni G Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia
description	Erdaw Tachbele,1,2 Samuel Kyobe,3 Fred Ashaba Katabazi,3 Edgar Kigozi,3 Savannah Mwesigwa,3 Moses Joloba,3 Alebachew Messele,1 Wondwossen Amogne,2 Mengistu Legesse,1 Rembert Pieper,4 Gobena Ameni1 1Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia; 2College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 3College of Health Sciences, Makerere University, Kampala, Uganda; 4Janssen Biopharma, South San Francisco, CA, USACorrespondence: Erdaw Tachbele Tel +251 911642880Email erdawt@yahoo.comPurpose: This study was conducted to investigate the drug resistance mutations and genetic diversity of HIV-1 in ART experienced patients in South Omo, Ethiopia.Patients and Methods: A cross-sectional study conducted on 253 adult patients attending ART clinics for ≥ 6 months in South Omo. Samples with VL ≥ 1000 copies/mL were considered as virological failures (VF) and their reverse transcriptase gene codons 90– 234 were sequenced using Illumina MiSeq. MinVar was used for the identification of the subtypes and drug resistance mutations. Phylogenetic tree was constructed by neighbor-joining method using the maximum likelihood model.Results: The median duration of ART was 51 months and 18.6% (47/253) of the patients exhibited VF. Of 47 viraemic patients, the genome of 41 were sequenced and subtype C was dominant (87.8%) followed by recombinant subtype BC (4.9%), M-09-CPX (4.9) and BF1 (2.4%). Of 41 genotyped subjects, 85.4% (35/41) had at least one ADR mutation. Eighty-one percent (33/41) of viraemic patients harbored NRTI resistance mutations, and 48.8% (20/41) were positive for NNRTI resistance mutations, with 43.9% dual resistance mutations. Among NRTI resistance mutations, M184V (73.2%), K219Q (63.4%) and T215 (56.1%) complex were the most mutated positions, while the most common NNRTI resistance mutations were K103N (24.4%), K101E, P225H and V108I 7.5% each. Active tuberculosis (aOR=13, 95% CI= 3.46– 29.69), immunological failure (aOR=3.61, 95% CI=1.26– 10.39), opportunistic infections (aOR=8.39, 95% CI= 1.75– 40.19), and poor adherence were significantly associated with virological failure, while rural residence (aOR 2.37; 95% CI: 1.62– 9.10, P= 0.05), immunological failures (aOR 2.37; 95% CI: 1.62– 9.10, P= 0.05) and high viral load (aOR 16; 95% CI: 5.35 51.59, P < 0.001) were predictors of ADR mutation among the ART experienced and viraemic study subjects.Conclusion: The study revealed considerable prevalence of VF and ADR mutation with the associated risk indicators. Regular virological monitoring and drug resistance genotyping methods should be implemented for better ART treatment outcomes of the nation.Keywords: HIV-1, genetic diversity, acquired drug resistance, ART experienced, South Omo, Ethiopia
format	article
author	Tachbele E Kyobe S Katabazi FA Kigozi E Mwesigwa S Joloba M Messele A Amogne W Legesse M Pieper R Ameni G
author_facet	Tachbele E Kyobe S Katabazi FA Kigozi E Mwesigwa S Joloba M Messele A Amogne W Legesse M Pieper R Ameni G
author_sort	Tachbele E
title	Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia
title_short	Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia
title_full	Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia
title_fullStr	Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia
title_full_unstemmed	Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia
title_sort	genetic diversity and acquired drug resistance mutations detected by deep sequencing in virologic failures among antiretroviral treatment experienced human immunodeficiency virus-1 patients in a pastoralist region of ethiopia
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/58cc8429429f41d986a5bd41e970d01e
work_keys_str_mv	AT tachbelee geneticdiversityandacquireddrugresistancemutationsdetectedbydeepsequencinginvirologicfailuresamongantiretroviraltreatmentexperiencedhumanimmunodeficiencyvirus1patientsinapastoralistregionofethiopia AT kyobes geneticdiversityandacquireddrugresistancemutationsdetectedbydeepsequencinginvirologicfailuresamongantiretroviraltreatmentexperiencedhumanimmunodeficiencyvirus1patientsinapastoralistregionofethiopia AT katabazifa geneticdiversityandacquireddrugresistancemutationsdetectedbydeepsequencinginvirologicfailuresamongantiretroviraltreatmentexperiencedhumanimmunodeficiencyvirus1patientsinapastoralistregionofethiopia AT kigozie geneticdiversityandacquireddrugresistancemutationsdetectedbydeepsequencinginvirologicfailuresamongantiretroviraltreatmentexperiencedhumanimmunodeficiencyvirus1patientsinapastoralistregionofethiopia AT mwesigwas geneticdiversityandacquireddrugresistancemutationsdetectedbydeepsequencinginvirologicfailuresamongantiretroviraltreatmentexperiencedhumanimmunodeficiencyvirus1patientsinapastoralistregionofethiopia AT jolobam geneticdiversityandacquireddrugresistancemutationsdetectedbydeepsequencinginvirologicfailuresamongantiretroviraltreatmentexperiencedhumanimmunodeficiencyvirus1patientsinapastoralistregionofethiopia AT messelea geneticdiversityandacquireddrugresistancemutationsdetectedbydeepsequencinginvirologicfailuresamongantiretroviraltreatmentexperiencedhumanimmunodeficiencyvirus1patientsinapastoralistregionofethiopia AT amognew geneticdiversityandacquireddrugresistancemutationsdetectedbydeepsequencinginvirologicfailuresamongantiretroviraltreatmentexperiencedhumanimmunodeficiencyvirus1patientsinapastoralistregionofethiopia AT legessem geneticdiversityandacquireddrugresistancemutationsdetectedbydeepsequencinginvirologicfailuresamongantiretroviraltreatmentexperiencedhumanimmunodeficiencyvirus1patientsinapastoralistregionofethiopia AT pieperr geneticdiversityandacquireddrugresistancemutationsdetectedbydeepsequencinginvirologicfailuresamongantiretroviraltreatmentexperiencedhumanimmunodeficiencyvirus1patientsinapastoralistregionofethiopia AT amenig geneticdiversityandacquireddrugresistancemutationsdetectedbydeepsequencinginvirologicfailuresamongantiretroviraltreatmentexperiencedhumanimmunodeficiencyvirus1patientsinapastoralistregionofethiopia
_version_	1718420727793713152

Genetic Diversity and Acquired Drug Resistance Mutations Detected by Deep Sequencing in Virologic Failures among Antiretroviral Treatment Experienced Human Immunodeficiency Virus-1 Patients in a Pastoralist Region of Ethiopia

Ejemplares similares