Applying Next-Generation Sequencing to Track HIV-1 Drug Resistance Mutations Circulating in Portugal

Viruses. 2024 Apr 17;16(4):622. doi: 10.3390/v16040622.

Abstract

Background: The global scale-up of antiretroviral treatment (ART) offers significant health benefits by suppressing HIV-1 replication and increasing CD4 cell counts. However, incomplete viral suppression poses a potential threat for the emergence of drug resistance mutations (DRMs), limiting ART options, and increasing HIV transmission.

Objective: We investigated the patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) among HIV-1 patients in Portugal.

Methods: Data were obtained from 1050 HIV-1 patient samples submitted for HIV drug resistance (HIVDR) testing from January 2022 to June 2023. Evaluation of DRM affecting viral susceptibility to nucleoside/tide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) was performed using an NGS technology, the Vela Diagnostics Sentosa SQ HIV-1 Genotyping Assay.

Results: About 71% of patients were ART naïve and 29% were experienced. Overall, 20% presented with any DRM. The prevalence of TDR and ADR was 12.6% and 41.1%, respectively. M184V, T215S, and M41L mutations for NRTI, K103N for NNRTI, and M46I/L for PIs were frequent in naïve and treated patients. E138K and R263K mutations against INSTIs were more frequent in naïve than treated patients. TDR and ADR to INSTIs were 0.3% and 7%, respectively. Patients aged 50 or over (OR: 1.81, p = 0.015), originating from Portuguese-speaking African countries (PALOPs) (OR: 1.55, p = 0.050), HIV-1 subtype G (OR: 1.78, p = 0.010), and with CD4 < 200 cells/mm3 (OR: 1.70, p = 0.043) were more likely to present with DRMs, while the males (OR: 0.63, p = 0.003) with a viral load between 4.1 to 5.0 Log10 (OR: 0.55, p = 0.003) or greater than 5.0 Log10 (OR: 0.52, p < 0.001), had lower chances of presenting with DRMs.

Conclusions: We present the first evidence on TDR and ADR to INSTI regimens in followed up patients presenting for healthcare in Portugal. We observed low levels of TDR to INSTIs among ART-naïve and moderate levels in ART-exposed patients. Regimens containing PIs could be an alternative second line in patients with intermediate or high-level drug resistance, especially against second-generation INSTIs (dolutegravir, bictegravir, and cabotegravir).

Keywords: Europe; HIV-1; INSTIs; NGS; Portugal; drug resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents* / pharmacology
  • Anti-HIV Agents* / therapeutic use
  • Drug Resistance, Viral* / genetics
  • Female
  • Genotype
  • HIV Infections* / drug therapy
  • HIV Infections* / epidemiology
  • HIV Infections* / virology
  • HIV-1* / drug effects
  • HIV-1* / genetics
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Portugal / epidemiology
  • Reverse Transcriptase Inhibitors / pharmacology
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Young Adult

Substances

  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors

Grants and funding

This research was funded by FCT in the Scopus of INTEGRIV project (PTDC/SAU-INF/31990/2017), FCT MARVEL (PTDC/SAU-PUB/4018/2021), Calouste Gulbenkian Foundation (FCG), under the ENVOLVE Ciência PALOP program that funded the HITOLA project (Nº.250466), Africa Research Excellence Fund (AREF) (AREF-312-CRUZ-F-C0931), Science and Technology Development Project (PDCT) within the scope of the MUTHIVAO project (Nº.36 MESCTI/PDCT/2022), and by funds from FCT to GHTM-UID/04413/2020 and LA-REAL-LA/P/0117/2020. SGS was funded by FCT, Portugal, through a program contract (CEECINST/00102/2018/CP1567/CT0040). CiiEM has provided support through Project 10.54499/UIDB/04585/2020, funded by FCT.