HIV-1 diversity and pre-treatment drug resistance in the era of integrase inhibitor among newly diagnosed ART-naïve adult patients in Luanda, Angola

Cruz S. Sebastião, Ana B. Abecasis, Domingos Jandondo, Joana M.K. Sebastião, João Vigário, Felícia Comandante, Marta Pingarilho, Bárbara Pocongo, Edson Cassinela, Fátima Gonçalves, Perpétua Gomes, Marta Giovanetti, Ngiambudulu M. Francisco, Euclides Sacomboio, Miguel Brito, Jocelyne Neto de Vasconcelos, Joana Morais, Victor Pimentel

Research output: Contribution to journalArticlepeer-review

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Abstract

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.

Original languageEnglish
Article number15893
JournalScientific Reports
Volume14
Issue number1
DOIs
Publication statusPublished - Dec 2024

Keywords

  • Angola
  • Drug resistance mutations
  • Genetic diversity
  • HIV-1
  • INSTI
  • NGS
  • Angola/epidemiology
  • Cross-Sectional Studies
  • Humans
  • Middle Aged
  • Male
  • HIV Integrase Inhibitors/therapeutic use
  • HIV Infections/drug therapy
  • Genetic Variation
  • Young Adult
  • Drug Resistance, Viral/genetics
  • HIV-1/genetics
  • Adult
  • Female
  • High-Throughput Nucleotide Sequencing
  • HIV Integrase/genetics

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