Applying Next-Generation Sequencing to Track HIV-1 Drug Resistance Mutations Circulating in Portugal
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
Affiliations
Victor Pimentel
Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Rua da Junqueira 100, 1349-008 Lisbon, Portugal
Marta Pingarilho
Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Rua da Junqueira 100, 1349-008 Lisbon, Portugal
Cruz S. Sebastião
Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Rua da Junqueira 100, 1349-008 Lisbon, Portugal
Mafalda Miranda
Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Rua da Junqueira 100, 1349-008 Lisbon, Portugal
Fátima Gonçalves
Laboratório de Biologia Molecular, Serviço de Patologia Clínica, Unidade Local de Saúde Lisboa Ocidental, Hospital Egas Moniz, 1349-019 Lisbon, Portugal
Joaquim Cabanas
Laboratório de Biologia Molecular, Serviço de Patologia Clínica, Unidade Local de Saúde Lisboa Ocidental, Hospital Egas Moniz, 1349-019 Lisbon, Portugal
Inês Costa
Laboratório de Biologia Molecular, Serviço de Patologia Clínica, Unidade Local de Saúde Lisboa Ocidental, Hospital Egas Moniz, 1349-019 Lisbon, Portugal
Isabel Diogo
Laboratório de Biologia Molecular, Serviço de Patologia Clínica, Unidade Local de Saúde Lisboa Ocidental, Hospital Egas Moniz, 1349-019 Lisbon, Portugal
Sandra Fernandes
Laboratório de Biologia Molecular, Serviço de Patologia Clínica, Unidade Local de Saúde Lisboa Ocidental, Hospital Egas Moniz, 1349-019 Lisbon, Portugal
Olga Costa
Biologia Molecular, Serviço de Patologia Clínica, Centro Hospitalar de Lisboa Central, 1150-199 Lisbon, Portugal
Rita Corte-Real
Biologia Molecular, Serviço de Patologia Clínica, Centro Hospitalar de Lisboa Central, 1150-199 Lisbon, Portugal
M. Rosário O. Martins
Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Rua da Junqueira 100, 1349-008 Lisbon, Portugal
Sofia G. Seabra
Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Rua da Junqueira 100, 1349-008 Lisbon, Portugal
Ana B. Abecasis
Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Rua da Junqueira 100, 1349-008 Lisbon, Portugal
Perpétua Gomes
Laboratório de Biologia Molecular, Serviço de Patologia Clínica, Unidade Local de Saúde Lisboa Ocidental, Hospital Egas Moniz, 1349-019 Lisbon, Portugal
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 3 (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).