Genetic landscape for majority and minority HIV-1 drug resistance mutations in antiretroviral therapy naive patients in Accra, Ghana

Appiah, Pious and Gbassana, Gaspah and Adusei-Poku, Mildred and Obeng, Billal Musah and Duedu, Kwabena and Sagoe, Kwamena William Coleman (2024) Genetic landscape for majority and minority HIV-1 drug resistance mutations in antiretroviral therapy naive patients in Accra, Ghana. Heliyon, 10 (12). e33180. ISSN 2405-8440

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The successful detection of drug-resistance mutations (DRMs) in HIV-1 infected patients has improved the management of HIV infection. Next-generation sequencing (NGS) to detect low-frequency mutations is predicted to be useful for efficiently testing minority drug resistance mutations, which could contribute to virological failure. This study employed Sanger sequencing and NGS to detect and compare minority and majority drug resistance mutations in HIV-1 strains in treatment-naive patients from Ghana.
From a previous study, 20 antiretroviral therapy (ART)-naive participants were selected for a cross-sectional study. Sanger sequencing and NGS techniques were used to detect the majority and minority HIV drug resistance (HIVDR) mutations, respectively, in the protease (PR) and partial reverse transcriptase (RT) genes. NGS detected mutations at 1 % and 5 % frequencies and Sanger sequencing at ≥20 % frequencies. The sequences obtained from NGS and Sanger sequencing platforms were submitted to the Stanford HIV drug resistance database for subtyping, mutation identification, and interpretations.
Sequences from the twenty participants where the CRF02_AG was the predominant strain (16, 80 %) were analyzed. NGS detected 25 mutations in the RT and PR genes, compared to 21 mutations by Sanger sequencing. Minority DRMs were detected at the prevalence of 55.0 % with NGS against 35 % DRMs by Sanger sequencing. One of the patients had eight different HIVDR variants, with two minority variants. These mutations were directed against PI (K20I and D30DN), NNRTI (Y181C, M23LM and V108I) and NRTI (K65R, M184I, and D67N).
The study affirms the usefulness of genomic sequencing for drug resistance testing in HIV. It further shows that Sanger sequencing alone may not be adequate to detect mutations and that NGS capacity should be developed and deployed in the Ghanaian clinical settings for patients living with HIV.

Item Type: Article
Identification Number:
15 June 2024Accepted
19 June 2024Published Online
Uncontrolled Keywords: HIV drug resistance, minority drug-resistance mutations, quasispecies, next-generation sequencing, virological failure
Subjects: CAH03 - biological and sport sciences > CAH03-01 - biosciences > CAH03-01-01 - biosciences (non-specific)
Divisions: Faculty of Health, Education and Life Sciences > College of Health and Care Professions
Depositing User: Gemma Tonks
Date Deposited: 26 Jun 2024 14:46
Last Modified: 26 Jun 2024 14:46

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