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
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Date
2021
Journal Title
Journal ISSN
Volume Title
Publisher
Infection and Drug Resistance
Abstract
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.
Description
Keywords
HIV-1, Genetic diversity, Acquired drug resistance, ART experienced
Citation
Tachbele, E., Kyobe, S., Katabazi, F. A., Kigozi, E., Mwesigwa, S., Joloba, M., ... & Ameni, G. (2021). 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. Infection and Drug Resistance, 4833-4847. https://doi.org/10.2147/IDR.S337485