HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019

Pingarilho, Marta; Pimentel, Victor; Miranda, María Adelaide; Silva, Ana Rita; Diniz, António; Ascenção, Bianca Branco; Piñeiro, Carmela; Koch, Carmen M.; Rodrigues, Catarina; Caldas, Carolina; Morais, Catarina M.; Faria, Domitília; Silva, Elisabete Gomes da; Teófilo, Eugénio; Monteiro, Fátima; Roxo, Fausto; Maltêz, Fernando; Rodrigues, Fernando; Gaião, Guilhermina; Ramos, Helena; Costa, Inês; Germano, Isabel; Simões, Joana; Oliveira, Joaquim; Ferreira, José A.; Poças, José; Cunha, José Saraiva da; Soares, Joaquim; Henriques, Júlia; Kamal, Mehnaz; Pedro, Liliana; Aleixo, Maria João; Goncąlves, Maria Joaõ; Manata, Maria José; Mouro, Margarida Martins; Serrado, Margarida; Caixeiro, Micaela; Marques, Nuno; Costa, Olga; Pacheco, Patrícia; Proença, Paula; Rodrigues, Paulo M. M.; Tavares, Raquel Aguiar; Abreu, Ricardo Correia de; Côrte‐Real, Rita; Serrão, Rosário; Castro, Rui Sarmento e; Nunes, Sofía; Faria, Telo; Baptista, Teresa; Martins, Maria do Rosário Oliveira; Gómes, Perpétua; Mendão, Luís; Simões, Daniel; Abecasis, Ana

doi:10.3389/fmicb.2022.823208

Cited by 6 publications

(6 citation statements)

References 34 publications

(37 reference statements)

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“…We also found that, for subtype B, the age at resistance test was associated with being in cluster, with a higher probability among individuals with younger age. This is in accordance with some other studies (18,25). Migration status was also associated with being in clusters: migrants infected with subtype B were mainly in a cluster, and migrants infected with subtype G were less likely to be in a cluster.…”

Section: Discussionsupporting

confidence: 94%

The role of Late Presenters on HIV-1 transmission clusters in Europe

Miranda

Pingarilho

Pimentel

et al. 2023

Preprint

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Background: Investigating the role of late presenters (LP) on HIV-1 transmission is important, as they can contribute to the onward spread of HIV-1 virus in the long period before diagnosis, when they are not aware of their HIV status Objective: To describe the clinical and socio-demographic characteristics of HIV-1 infected individuals followed in Europe, to characterize patients in clusters and to compare transmission clusters (TC) in LP vs non-late presenters (NLP) populations. Methods: Clinical, socio-demographic and genotypic information from 38531 HIV-1 infected patients was collected from the EuResist Integrated Database (EIDB) between 1981 and 2019. Sequences were aligned using VIRULIGN. Maximum likelihood (ML) phylogenies were constructed using FastTree. Putative transmission clusters were identified using ClusterPicker v1.332. Statistical analyses were performed using R. Results: 32652 (84.7%) sequences were from subtype B, 3603 (9.4%) were from subtype G, and 2276 (5.9%) were from subtype A. The median age was 33 (IQR: 26.0-41.0) years old and 75.5% of patients were males. The main transmission route was through homosexual (MSM) contact (36.9%) and 86.4% were originated from Western Europe. Most patients were native (84.2%), 59.6% had a chronic infection, and 73.4% had acquired drug resistance (ADR). CD4 count and viral load at diagnosis (log10) presented a median of 341 cells/mm3, and of log10 4.3 copies/mL, respectively. 51.4% of patients were classified as LP and 21.6% patients were inside TCs. Most patients from subtype B (85.6%) were in clusters, compared to subtypes A (5.2%) and G (9.2%). Phylogenetic analyses showed consistent clustering of MSM individuals. In subtype A, patients in TCs were more frequently MSM patients and with a recent infection. For subtype B, patients in TCs were more frequently those with older age (≥ 56), MSM transmission route, originating from Western Europe, migrants, and with a recent infection. For subtype G, patients in TC were more frequently patients with recent infection and migrants. When analysing cluster size, we found that NLP more frequently belonged to large clusters (>8 patients) when compared to LP. Conclusion: While late presentation is still a threat to HIV-1 transmission, LP individuals are more present either outside or in small clusters, indicating a limited role of late presentation to HIV-1 transmission.

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Section: Discussionsupporting

confidence: 94%

The role of Late Presenters on HIV-1 transmission clusters in Europe

Miranda

Pingarilho

Pimentel

et al. 2023

Preprint

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“…The detection of SDRMs in the present study was consistent with other recent studies published in Europe [ 6 , 7 , 8 ], making our findings one of the more up-to-date studies including the surveillance of resistance to INSTIs. The rate of SDRMs conferring resistance to NRTIs remained stable and similar to a previous study conducted in Portugal [ 7 ]. Interestingly, M184V continues to be transmitted at a very low proportion, with most SDRMs being transmitted as singletons.…”

Section: Discussionsupporting

confidence: 93%

“…Upon identification of a DRM, ART regimens are usually modified accordingly, replacing ineffective drugs with those that are expected to effectively suppress the viral replication [ 5 ]. The European multi-center cohort study conducted in the past 10 years and the Portuguese HIV drug resistance (HIVDR) study conducted in 2021 showed that the prevalence of HIV resistance increased over time [ 6 , 7 , 8 ]. Based on this evidence, the World Health Organization (WHO) stated that further investigation on this subject is necessary in this era of a global scale-up of ART to achieve the 95-95-95 targets [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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

Pimentel,

Pingarilho,

Sebastião

et al. 2024

Viruses

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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).

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“…In subtypes A and B, there were differences concerning age, recentness of infection, and viral load. In subtypes A and B, younger individuals were associated with being NLPs inside clusters, and this is in accordance with other studies associating younger age with clustering [22,27]. Furthermore, in subtype B, the LPs inside clusters were older (more than 31 y/o), with a higher and growing proportion of LPs in clusters as age increased.…”

Section: Discussionsupporting

confidence: 90%

The Role of Late Presenters in HIV-1 Transmission Clusters in Europe

Miranda,

Pimentel,

Gomes

et al. 2023

Viruses

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Background: Investigating the role of late presenters (LPs) in HIV-1 transmission is important, as they can contribute to the onward spread of HIV-1 virus before diagnosis, when they are not aware of their HIV status. Objective: To characterize individuals living with HIV-1 followed up in Europe infected with subtypes A, B, and G and to compare transmission clusters (TC) in LP vs. non-late presenter (NLP) populations. Methods: Information from a convenience sample of 2679 individuals living with HIV-1 was collected from the EuResist Integrated Database between 2008 and 2019. Maximum likelihood (ML) phylogenies were constructed using FastTree. Transmission clusters were identified using Cluster Picker. Statistical analyses were performed using R. Results: 2437 (91.0%) sequences were from subtype B, 168 (6.3%) from subtype A, and 74 (2.8%) from subtype G. The median age was 39 y/o (IQR: 31.0–47.0) and 85.2% of individuals were males. The main transmission route was via homosexual (MSM) contact (60.1%) and 85.0% originated from Western Europe. In total, 54.7% of individuals were classified as LPs and 41.7% of individuals were inside TCs. In subtype A, individuals in TCs were more frequently males and natives with a recent infection. For subtype B, individuals in TCs were more frequently individuals with MSM transmission route and with a recent infection. For subtype G, individuals in TCs were those with a recent infection. When analyzing cluster size, we found that LPs more frequently belonged to small clusters (<8 individuals), particularly dual clusters (2 individuals). Conclusion: LP individuals are more present either outside or in small clusters, indicating a limited role of late presentation to HIV-1 transmission.

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HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019

Cited by 6 publications

References 34 publications

The role of Late Presenters on HIV-1 transmission clusters in Europe

The role of Late Presenters on HIV-1 transmission clusters in Europe

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

The Role of Late Presenters in HIV-1 Transmission Clusters in Europe

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