Percorrer por autor "Pingarilho, Marta"
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- Applying next-generation sequencing to track HIV-1 drug resistance mutations circulating in PortugalPublication . Pimentel, Victor; Pingarilho, Marta; Sebastião, Cruz S.; Miranda, Mafalda; Gonçalves, Fátima; Cabanas, Joaquim; Costa, Inês; Diogo, Isabel; Fernandes, Sandra; Costa, Olga; Corte-Real, Rita; Martins, M. Rosário O.; Seabra, Sofia G.; Abecasis, Ana B.; Gomes, PerpétuaBackground: 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).
- Characterization of a large cluster of HIV-1 A1 infections detected in Portugal and connected to several Western European countriesPublication . Araújo, Pedro M. M.; Carvalho, Alexandre; Pingarilho, Marta; BEST-HOPE study group; Abecasis, Ana B.; Osório, Nuno S.HIV-1 subtypes associate with differences in transmission and disease progression. Thus, the existence of geographic hotspots of subtype diversity deepens the complexity of HIV-1/AIDS control. The already high subtype diversity in Portugal seems to be increasing due to infections with sub-subtype A1 virus. We performed phylogenetic analysis of 65 A1 sequences newly obtained from 14 Portuguese hospitals and 425 closely related database sequences. 80% of the A1 Portuguese isolates gathered in a main phylogenetic clade (MA1). Six transmission clusters were identified in MA1, encompassing isolates from Portugal, Spain, France, and United Kingdom. The most common transmission route identified was men who have sex with men. The origin of the MA1 was linked to Greece, with the first introduction to Portugal dating back to 1996 (95% HPD: 1993.6–1999.2). Individuals infected with MA1 virus revealed lower viral loads and higher CD4+ T-cell counts in comparison with those infected by subtype B. The expanding A1 clusters in Portugal are connected to other European countries and share a recent common ancestor with the Greek A1 outbreak. The recent expansion of this HIV-1 subtype might be related to a slower disease progression leading to a population level delay in its diagnostic.
- Cruising Venues as a Context for HIV Risky Behavior Among Men Who Have Sex With MenPublication . Gama, Ana; Abecasis, Ana; Pingarilho, Marta; Mendão, Luís; Martins, Maria O.; Barros, Henrique; Dias, SóniaWe examined differences in sexual risk behaviors, HIV prevalence, and demographic characteristics between men who have sex with men (MSM) who visit different types of venues to meet sexual partners, and identified correlates of high-risk behaviors. A cross-sectional behavioral survey was conducted with a venue-based sample of 1011 MSM in Portugal. Overall, 36.3 % of MSM usually visit cruising venues to meet sexual partners (63.7 % only visit social gay venues). Cruising venues' visitors reported higher HIV prevalence (14.6 % [95 % CI 11-18 %] vs. 5.5 % [95 % CI 4-7 %]). Visiting cruising venues was more likely among those older, reporting high number of male sexual partners, group sex, and unprotected anal sex with a partner whose HIV status was unknown. Cruising venues play an important role in increasing risk of HIV transmission among MSM who frequent them. Venue-focused behavioral interventions that promote healthy sexual behaviors are needed.
- Determinants of HIV late presentation among men who have sex with men in Portugal (2014–2019) : who’s being left behind?Publication . Abrantes, Ricardo; Pimentel, Victor; Miranda, Mafalda N. S.; Silva, Ana Rita; Diniz, António; Ascenção, Bianca; Piñeiro, Carmela; Koch, Carmo; Rodrigues, Catarina; Caldas, Cátia; Morais, Célia; Faria, Domitília; Silva, Elisabete Gomes da; Teófilo, Eugénio; Monteiro, Fátima; Roxo, Fausto; Maltez, Fernando; Rodrigues, Fernando; Gaião, Guilhermina; Ramos, Helena; Costa, Inês; Germano, Isabel; Simões, Joana; Oliveira, Joaquim; Ferreira, José; Poças, José; Cunha, José Saraiva da; Soares, Jorge; Fernandes, Sandra; Mansinho, Kamal; Pedro, Liliana; Aleixo, Maria João; Gonçalves, Maria João; Manata, Maria José; Mouro, Margarida; Serrado, Margarida; Caixeiro, Micaela; Marques, Nuno; Costa, Olga; Pacheco, Patrícia; Proença, Paula; Rodrigues, Paulo; Pinho, Raquel; Tavares, Raquel; Abreu, Ricardo Correia de; Côrte-Real, Rita; Serrão, Rosário; Castro, Rui Sarmento e; Nunes, Sofia; Faria, Telo; Baptista, Teresa; Simões, Daniel; Mendão, Luís; Martins, M. Rosário O.; Gomes, Perpétua; Pingarilho, Marta; Abecasis, Ana B.; the BESTHOPE Study GroupIntroduction: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019. Methods: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP). Results: The median age was 31 years, 51% had a current income between 501–1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP. Conclusion: Our study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.
- Determinants of HIV late presentation among men who have sex with men in Portugal (2014–2019): who’s being left behind?Publication . Abrantes, Ricardo; Pimentel, Victor; Miranda, Mafalda N. S.; Silva, Ana Rita; Diniz, António; Ascenção, Bianca; Piñeiro, Carmela; Koch, Carmo; Rodrigues, Catarina; Caldas, Cátia; Morais, Célia; Faria, Domitília; Gomes da Silva, Elisabete; Teófilo, Eugénio; Monteiro, Fátima; Roxo, Fausto; Maltez, Fernando; Rodrigues, Fernando; Gaião, Guilhermina; Ramos, Helena; Costa, Inês; Germano, Isabel; Simões, Joana; Oliveira, Joaquim; Ferreira, José; Poças, José; Saraiva da Cunha, José; Soares, Jorge; Fernandes, Sandra; Mansinho, Kamal; Pedro, Liliana; Aleixo, Maria João; Gonçalves, Maria João; Manata, Maria José; Mouro, Margarida; Serrado, Margarida; Caixeiro, Micaela; Marques, Nuno; Costa, Olga; Pacheco, Patrícia; Proença, Paula; Rodrigues, Paulo; Pinho, Raquel; Tavares, Raquel; Correia de Abreu, Ricardo; Côrte-Real, Rita; Serrão, Rosário; Sarmento e Castro, Rui; Nunes, Sofia; Faria, Telo; Baptista, Teresa; Simões, Daniel; Mendão, Luís; Martins, M. Rosário O.; Gomes, Perpétua; Pingarilho, Marta; Abecasis, Ana B.Introduction: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019. Methods: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP). Results: The median age was 31 years, 51% had a current income between 501-1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP. Conclusion: Our study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.
- Determinants of HIV-1 transmission clusters and transmitted drug resistance in men who have sex with men : a multicenter study in Portugal (2014-2019)Publication . Abrantes, Ricardo; Pimentel, Victor; Sebastião, Cruz; Miranda, Mafalda N. S.; Seabra, Sofia; Silva, Ana Rita; Diniz, António; Ascenção, Bianca; Piñeiro, Carmela; Koch, Carmo; Rodrigues, Catarina; Caldas, Cátia; Morais, Célia; Faria, Domitília; Silva, Elisabete Gomes da; Teófilo, Eugénio; Monteiro, Fátima; Roxo, Fausto; Maltez, Fernando; Rodrigues, Fernando; Gaião, Guilhermina; Ramos, Helena; Costa, Inês; Diogo, Isabel; Germano, Isabel; Simões, Joana; Oliveira, Joaquim; Ferreira, José; Poças, José; Cunha, José Saraiva da; Soares, Jorge; Mansinho, Kamal; Pedro, Liliana; Aleixo, Maria João; Gonçalves, Maria João; Manata, Maria José; Mouro, Margarida; Serrado, Margarida; Caixeiro, Micaela; Marques, Nuno; Costa, Olga; Pacheco, Patrícia; Proença, Paula; Rodrigues, Paulo; Pinho, Raquel; Tavares, Raquel; Abreu, Ricardo Correia de; Côrte-Real, Rita; Serrão, Rosário; Castro, Rui Sarmento e; Nunes, Sofia; Faria, Telo; Baptista, Teresa; Simões, Daniel; Mendão, Luís; Martins, M. Rosário O.; Gomes, Perpétua; Pingarilho, Marta; Abecasis, Ana B.; On behalf of BESTHOPE Study GroupIntroduction: In the EU/EEA, men who have sex with men (MSM) is a priority group for the prevention and control of HIV-1 infection. In Portugal, the 2023 HIV incidence rate was 8.2 per 100,000 inhabitants, with 876 new infections, 41.7% in MSM. We aim to characterize HIV-1 transmission clusters (TC) and transmitted drug resistance (TDR) and its sociodemographic, behavioral, clinical, and viral genomic determinants in MSM newly diagnosed in Portugal between 2014 and 2019. Methods: A total of 340 MSM newly diagnosed with HIV-1 infection at 17 hospitals in Portugal were included. TC was identified with branch support ≥90% and 1.5% genetic distance. Logistic regression models were used to examine factors associated with TC and TDR. Results: We identified 38 TC with 104 MSM, which includes 81 (26.6%) of the 305 MSM from our sample included in cluster analysis. The overall prevalence of TDR was 8.2%. Only HIV-1 subtype C was significantly associated with TDR. Overall, 10.5% of the clusters had at least 1 surveillance drug resistance mutation. There was no significant difference in the prevalence of TDR or the proportion of Portuguese and migrant MSM inside and outside clusters. Age at diagnosis, district of residence, unprotected sex with a woman, HIV testing, presenter status, and HIV-1 subtype were significantly associated with TC. Conclusion: Specific subgroups of MSM are contributing to HIV-1 clustered transmission in Portugal. However, no association was found between TDR and sociodemographic or behavioral factors. Directed prevention measures should focus on those subgroups.
- Differential patterns of postmigration HIV-1 infection acquisition among Portuguese immigrants of different geographical originsPublication . Pimentel, Victor Figueiredo; Pingarilho, Marta; Sole, Giordano; Alves, Daniela; Miranda, Mafalda; Diogo, Isabel; Fernandes, Sandra; Pineda-Pena, Andrea; Martins, M. Rosário O; Camacho, Ricardo; Gomes, Perpétua; Abecasis, Ana B.Objective: To investigate the dynamics of phylogenetic transmission clusters involving immigrants of Portuguese Speaking Countries living in Portugal. Design/methods: We included genomic sequences, sociodemographic and clinical data from 772 HIV migrants followed in Portugal between 2001 and 2017. To reconstruct HIV-1 transmission clusters, we applied phylogenetic inference from 16 454 patients: 772 migrants, 2973 Portuguese and 12 709 global controls linked to demographic and clinical data. Transmission clusters were defined using: clusters with SH greater than 90% (phylogenetic support), genetic distance less than 3.5% and clusters that included greater than 66% of patients from one specific geographic origin compared with the total of sequences within the cluster. Logistic regression was performed to assess factors associated with clustering. Results: Three hundred and six (39.6%) of migrants were included in transmission clusters. This proportion differed substantially by region of origin [Brazil 54% vs. Portuguese Speaking African Countries (PALOPs) 36%, P < 0.0001] and HIV-1 infecting subtype (B 52%, 43% subtype G and 32% CRF02_AG, P < 0.001). Belonging to a transmission cluster was independently associated with treatment-naive patients, CD4+ greater than 500, with recent calendar years of sampling, origin from PALOPs and with seroconversion. Among Brazilian migrants – mainly infected with subtype B – 40.6% were infected by Portuguese. Among migrants from PALOPs – mainly infected with subtypes G and CFR02_AG – the transmission occurred predominantly within the migrants’ community (53 and 80%, respectively). Conclusion: The acquisition of infection among immigrants living in Portugal differs according to the country of origin. These results can contribute to monitor the HIV epidemic and prevent new HIV infections among migrants.
- Drivers of HIV-1 transmission: The Portuguese casePublication . Pineda-Peña, Andrea-Clemencia; Pingarilho, Marta; Li, Guangdi; Vrancken, Bram; Libin, Pieter; Gomes, Perpétua; Camacho, Ricardo Jorge; Theys, Kristof; Abecasis, Ana Barroso; Portuguese HIV-1 Resistance Study GroupBackground Portugal has one of the most severe HIV-1 epidemics in Western Europe. Two subtypes circulate in parallel since the beginning of the epidemic. Comparing their transmission patterns and its association with transmitted drug resistance (TDR) is important to pinpoint transmission hotspots and to develop evidence-based treatment guidelines. Methods Demographic, clinical and genomic data were collected from 3599 HIV-1 naive patients between 2001 and 2014. Sequences obtained from drug resistance testing were used for subtyping, TDR determination and transmission clusters (TC) analyses. Results In Portugal, transmission of subtype B was significantly associated with young males, while transmission of subtype G was associated with older heterosexuals. In Portuguese originated people, there was a decreasing trend both for prevalence of subtype G and for number of TCs in this subtype. The active TCs that were identified (i.e. clusters originated after 2008) were associated with subtype B-infected males residing in Lisbon. TDR was significantly different when comparing subtypes B (10.8% [9.5–12.2]) and G (7.6% [6.4–9.0]) (p = 0.001). Discussion TC analyses shows that, in Portugal, the subtype B epidemic is active and fueled by young male patients residing in Lisbon, while transmission of subtype G is decreasing. Despite similar treatment rates for both subtypes in Portugal, TDR is significantly different between subtypes.
- Emerging patterns in HIV integrase resistancePublication . Veloso, Margarida; Ribeiro, Marta; Cabanas, Joaquim; Gonçalves, Fátima; Fernandes, Sandra; Diogo, Isabel; Costa, Inês; Pimentel, Victor; Pingarilho, Marta; Abecasis, Ana; Gomes, PerpétuaWe assessed integrase resistance in 837 treatment-experienced people with HIV (PWH) with virological failure (2022–2024) in Portugal. Major resistance mutations were found in 5.5%, with N155H and R263K being the most common. Resistance was more frequent in non-B subtypes and often co-occurred with resistance to other antiretroviral classes. Though prevalence remains low, the findings highlight the need for continued surveillance to inform treatment decisions, especially as integrase inhibitors like dolutegravir, bictegravir and cabotegravir become more widely used.
- Genetic diversity and antiretroviral resistance in HIV-1-infected patients newly diagnosed in Cabo VerdePublication . Leal, Silvânia da Veiga; Pimentel, Victor; Gonçalves, Paloma; Araújo, Isabel Inês Monteiro de Pina; Parreira, Ricardo; Taveira, Nuno; Pingarilho, Marta; Abecasis, Ana B.The high genetic variability of HIV-1 and the emergence of transmitted drug resistance (TDR) can impact treatment efficacy. In this study, we investigated the prevalent HIV-1 genotypes and drug-resistance-associated mutations in drug-naïve HIV-1 individuals in Cabo Verde. The study, conducted between 2018 and 2019, included drug-naïve HIV-1 individuals from the São Vicente, Boa Vista, Fogo, and Santiago islands. The HIV-1 pol gene was sequenced using Sanger sequencing. TDR was identified using the Stanford Calibrated Population Resistance tool, and resistance levels to different drugs were interpreted with the Stanford HIV database. The genetic diversity of HIV-1 was determined through phylogenetic analysis, and epidemiological and behavioural data were collected via questionnaires. Of the 73 participants, the majority were male (52.1%). The CRF02_AG recombinant form predominated (41.1%), followed by subtype G (37.0%). The overall prevalence of TDR was 9.6%. Nucleoside Reverse Transcriptase Inhibitor (NRTI) mutations occurred in 2.7% of individuals, while Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) mutations occurred in 9.6%. The most prevalent mutations were K103N (5.5%) and M184V (2.7%). No protease- or integrase-associated mutations were found. The high levels of resistance to NNRTIs found demonstrate the need for surveillance of resistance mutations to ensure the efficacy and durability of the current therapeutic regimen, which includes Dolutegravir.
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