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; Samuel Kyobe; Fred Ashaba Katabazi; Edgar Kigozi; Savannah Mwesigwa; Moses Joloba; Alebachew Messele; Wondwossen Amogne; Mengistu Legesse; Rembert Pieper; Gobena Ameni

doi:10.2147/IDR.S337485

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

Infect Drug Resist. 2021 Nov 18:14:4833-4847. doi: 10.2147/IDR.S337485. eCollection 2021.

Authors

Affiliations

¹ Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.
² College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
³ College of Health Sciences, Makerere University, Kampala, Uganda.
⁴ Janssen Biopharma, South San Francisco, CA, USA.

Abstract

Purpose: 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: ART experienced; Ethiopia; HIV-1; South Omo; acquired drug resistance; genetic diversity.

Grants and funding

U01 HG007472/HG/NHGRI NIH HHS/United States