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

• Published in: Viruses
• Main Authors: Victor Pimentel, Marta Pingarilho, Cruz S. Sebastião, Mafalda Miranda, Fátima Gonçalves, Joaquim Cabanas, Inês Costa, Isabel Diogo, Sandra Fernandes, Olga Costa, Rita Corte-Real, M. Rosário O. Martins, Sofia G. Seabra, Ana B. Abecasis, Perpétua Gomes
• Format: Article
• Language: English
• Published: MDPI AG 2024-04-01
• Subjects: HIV-1; drug resistance; INSTIs; NGS; Portugal; Europe
• Online Access: https://www.mdpi.com/1999-4915/16/4/622

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, <i>p</i> = 0.015), originating from Portuguese-speaking African countries (PALOPs) (OR: 1.55, <i>p</i> = 0.050), HIV-1 subtype G (OR: 1.78, <i>p</i> = 0.010), and with CD4 < 200 cells/mm³ (OR: 1.70, <i>p</i> = 0.043) were more likely to present with DRMs, while the males (OR: 0.63, <i>p</i> = 0.003) with a viral load between 4.1 to 5.0 Log₁₀ (OR: 0.55, <i>p</i> = 0.003) or greater than 5.0 Log₁₀ (OR: 0.52, <i>p</i> < 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).