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
| Autor: | Edgar Kigozi, Moses Joloba, Rembert Pieper, Samuel Kyobe, Wondwossen Amogne, Fred A Katabazi, Savannah Mwesigwa, Gobena Ameni, Mengistu Legesse, Alebachew Messele, Erdaw Tachbele |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Drug resistance medicine.disease_cause Deep sequencing acquired drug resistance Internal medicine Antiretroviral treatment Medicine Pharmacology (medical) Genotyping Original Research Pharmacology Genetic diversity Mutation business.industry genetic diversity Resistance mutation South Omo Infectious Diseases Infection and Drug Resistance HIV-1 Ethiopia ART experienced business Corrigendum Viral load |
| Zdroj: | Infection and Drug Resistance |
| ISSN: | 1178-6973 |
| Popis: | 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 90â 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= 3.46â 29.69), immunological failure (aOR=3.61, 95% CI=1.26â 10.39), opportunistic infections (aOR=8.39, 95% CI= 1.75â 40.19), and poor adherence were significantly associated with virological failure, while rural residence (aOR 2.37; 95% CI: 1.62â 9.10, P= 0.05), immunological failures (aOR 2.37; 95% CI: 1.62â 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 |
| Databáze: | OpenAIRE |
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