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Advisor(s)
Abstract(s)
The surveillance of drug resistance in the HIV-1 naïve population remains critical to optimizing the effectiveness of antiretroviral therapy (ART), mainly in the era of integrase strand transfer inhibitor (INSTI) regimens. Currently, there is no data regarding resistance to INSTI in Angola since Dolutegravir-DTG was included in the first-line ART regimen. Herein, we investigated the HIV-1 genetic diversity and pretreatment drug resistance (PDR) profile against nucleoside/tide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and INSTIs, using a next-generation sequencing (NGS) approach with MinION, established to track and survey DRMs in Angola. This was a cross-sectional study comprising 48 newly HIV-diagnosed patients from Luanda, Angola, screened between March 2022 and May 2023. PR, RT, and IN fragments were sequenced for drug resistance and molecular transmission cluster analysis. A total of 45 out of the 48 plasma samples were successfully sequenced. Of these, 10/45 (22.2%) presented PDR to PIs/NRTIs/NNRTIs. Major mutations for NRTIs (2.2%), NNRTIs (20%), PIs (2.2%), and accessory mutations against INSTIs (13.3%) were detected. No major mutations against INSTIs were detected. M41L (2%) and I85V (2%) mutations were detected for NRTI and PI, respectively. K103N (7%), Y181C (7%), and K101E (7%) mutations were frequently observed in NNRTI. The L74M (9%) accessory mutation was frequently observed in the INSTI class. HIV-1 pure subtypes C (33%), F1 (17%), G (15%), A1 (10%), H (6%), and D (4%), CRF01_AG (4%) were observed, while about 10% were recombinant strains. About 31% of detected HIV-1C sequences were in clusters, suggesting small-scale local transmission chains. No major mutations against integrase inhibitors were detected, supporting the continued use of INSTI in the country. Further studies assessing the HIV-1 epidemiology in the era of INSTI-based ART regimens are needed in Angola.
Description
This research was funded by the Fundação Calouste Gulbenkian (FCG), under the ENVOLVE Ciência PALOP
program that funded the HITOLA project (Number 250466), AREF (AREF-312-CRUZ-F-C0931), Science
and Technology Development Project (PDCT) within the scope of the MUTHIVAO project (Number 36
MESCTI/PDCT/2022), FCT MARVEL (PTDC/SAU-PUB/4018/2021), FCT GHTM-UID/04413/2020 and
LA-REAL-LA/P/0117/2020.
Keywords
Genetics Drug resistance mutations Genetic diversity HIV-1 INSTI Integrase strand transfer inhibitor NGS Next-generation sequencing Angola Luanda PTDC/SAU-PUB/4018/2021 GHTM-UID/04413/2020 LA-REAL-LA/P/0117/2020 AREF-312-CRUZ-F-C0931 MESCTI/PDCT/2022
Citation
Sebastião CS, Abecasis AB, Jandondo D, Sebastião JM, Vigário J, Brito M, et al. HIV-1 diversity and pre-treatment drug resistance in the era of integrase inhibitor among newly diagnosed ART-naïve adult patients in Luanda, Angola. Sci Rep. 2024;14(1):15893.
