Percorrer por autor "Martins, M. Rosário O."
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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).
- 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.
- Increasing prevalence of HIV-1 transmitted drug resistance in Portugal: implications for first line treatment recommendationsPublication . Pingarilho, Marta; Pimentel, Victor; Diogo, Isabel; Fernandes, Sandra; Miranda, Mafalda; Pineda-Pena, Andrea; Libin, Pieter; Theys, Kristof; Martins, M. Rosário O.; Vandamme, Anne-Mieke; Camacho, Ricardo; Gomes, Perpétua; Abecasis, Ana; Portuguese HIV-1 Resistance Study GroupIntroduction: Treatment for All recommendations have allowed access to antiretroviral (ARV) treatment for an increasing number of patients. This minimizes the transmission of infection but can potentiate the risk of transmitted (TDR) and acquired drug resistance (ADR). Objective: To study the trends of TDR and ADR in patients followed up in Portuguese hospitals between 2001 and 2017. Methods: In total, 11,911 patients of the Portuguese REGA database were included. TDR was defined as the presence of one or more surveillance drug resistance mutation according to the WHO surveillance list. Genotypic resistance to ARV was evaluated with Stanford HIVdb v7.0. Patterns of TDR, ADR and the prevalence of mutations over time were analyzed using logistic regression. Results and Discussion: The prevalence of TDR increased from 7.9% in 2003 to 13.1% in 2017 (p < 0.001). This was due to a significant increase in both resistance to nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleotide reverse transcriptase inhibitors (NNRTIs), from 5.6% to 6.7% (p = 0.002) and 2.9% to 8.9% (p < 0.001), respectively. TDR was associated with infection with subtype B, and with lower viral load levels (p < 0.05). The prevalence of ADR declined from 86.6% in 2001 to 51.0% in 2017 (p < 0.001), caused by decreasing drug resistance to all antiretroviral (ARV) classes (p < 0.001). Conclusions: While ADR has been decreasing since 2001, TDR has been increasing, reaching a value of 13.1% by the end of 2017. It is urgently necessary to develop public health programs to monitor the levels and patterns of TDR in newly diagnosed patients.
- MARVEL-minimising the emergence and dissemination of HIV-1 drug resistance in Portuguese-speaking African Countries (PALOP) : low-cost portable NGS platform for HIV-1 surveillance in AfricaPublication . Sebastião, Cruz S.; Pingarilho, Marta; Bathy, Jamila; Bonfim, Elizângela; Toancha, Katia; Miranda, Mafalda N. S.; Martins, M. Rosário O.; Gomes, Perpétua; Lázaro, Lazismino; Pina-Araujo, Isabel; Nhampossa, Tacilta; Leal, Silvania; Abecasis, Ana B.; Pimentel, VictorBackground: HIV-1 infections remain a global public health concern. Scaled-up antiretroviral treatment (ART) is crucial for reducing morbidity and mortality related to HIV/AIDS. The emergence of drug-resistance mutations (DRMs) compromises viral suppression and contributes to the continued HIV-1 transmission. Several reports indicate a recent increase in acquired (ADR) and transmitted (TDR) drug resistance in Africa, probably linked to the lack of implementation of HIV drug resistance (HIVDR) testing and suboptimal treatment adherence. Herein, we will develop a low-cost protocol using third-generation sequencing (Oxford Nanopore Technology) for HIV-1 surveillance in Portuguese-speaking African Countries - PALOP [Angola (AO), Cape Verde (CV), Mozambique (MZ), and Sao Tome & Principe (STP)]. Methods: This is a multicentric cross-sectional study that includes around 600 adult patients newly diagnosed with HIV-1 in the PALOP. An epidemiological questionnaire previously validated by our research team will be used to collect sociodemographic and clinical data. Also, whole blood samples will be collected and the plasma samples will be subjected to drug resistance testing using an in-house low-cost NGS protocol. Data analysis will involve bioinformatics, biostatistics and machine learning techniques to generate accurate and up-to-date information about HIV-1 genetic diversity, ADR and TDR. Discussion: The implementation of this low-cost NGS platform for HIV-1 surveillance in the PALOP will allow: (i) to increase DRM surveillance capacity in resource-limited settings; (ii) to understand the pattern and determinants of dissemination of resistant HIV-1 strains; and (iii) to promote the development of technical and scientific skills of African researchers for genomic surveillance of viral pathogens and bioinformatics analysis. These objectives will contribute to reinforcing the capacity to combat HIV infection in Africa by optimizing the selection of ART regimens, improving viral suppression, and reducing ADR or TDR prevalence in PALOPs, with relevant implications for public health.
- Molecular epidemiology of HIV-1 infected migrants followed up in Portugal: trends between 2001–2017Publication . Pimentel, Victor; Pingarilho, Marta; Alves, Daniela; Diogo, Isabel; Fernandes, Sandra; Miranda, Mafalda; Pineda-Peña, Andrea-Clemencia; Libin, Pieter; Martins, M. Rosário O.; Vandamme, Anne-Mieke; Camacho, Ricardo; Gomes, Perpétua; Abecasis, AnaMigration is associated with HIV-1 vulnerability. Objectives: To identify long-term trends in HIV-1 molecular epidemiology and antiretroviral drug resistance (ARV) among migrants followed up in Portugal Methods: 5177 patients were included between 2001 and 2017. Rega, Scuel, Comet, and jPHMM algorithms were used for subtyping. Transmitted drug resistance (TDR) and Acquired drug resistance (ADR) were defined as the presence of surveillance drug resistance mutations (SDRMs) and as mutations of the IAS-USA 2015 algorithm, respectively. Statistical analyses were performed. Results: HIV-1 subtypes infecting migrants were consistent with the ones prevailing in their countries of origin. Over time, overall TDR significantly increased and specifically for Non-nucleoside reverse transcriptase inhibitor (NNRTIs) and Nucleoside reverse transcriptase inhibitor (NRTIs). TDR was higher in patients from Mozambique. Country of origin Mozambique and subtype B were independently associated with TDR. Overall, ADR significantly decreased over time and specifically for NRTIs and Protease Inhibitors (PIs). Age, subtype B, and viral load were independently associated with ADR. Conclusions: HIV-1 molecular epidemiology in migrants suggests high levels of connectivity with their country of origin. The increasing levels of TDR in migrants could indicate an increase also in their countries of origin, where more efficient surveillance should occur.
- Sociodemographic, clinical, and behavioral factors associated with sexual transmitted infection among HIV-1 positive migrants in Portugal : are there differences between sexes?Publication . Miranda, Mafalda N. S.; Pimentel, Victor; Graça, Jacqueline; Seabra, Sofia G.; Sebastião, Cruz S.; Diniz, António; Faria, Domitília; Teófilo, Eugénio; Roxo, Fausto; Maltez, Fernando; Germano, Isabel; Oliveira, Joaquim; Ferreira, José; Poças, José; Mansinho, Kamal; Mendão, Luís; Gonçalves, Maria João; Mouro, Margarida; Marques, Nuno; Pacheco, Patrícia; Proença, Paula; Tavares, Raquel; Abreu, Ricardo Correia de; Serrão, Rosário; Faria, Telo; BESTHOPE Study Group; Martins, M. Rosário O.; Gomes, Perpétua; Abecasis, Ana B.; Pingarilho, MartaIntroduction: Sexually transmitted infections (STIs) continue to occur at high levels. According to the WHO, each year there are an estimated 374 million new infections with syphilis, gonorrhea, chlamydia, and trichomoniasis. STIs are associated with an increased risk of acquiring HIV infection. Migrants are reportedly highly affected by STIs. Objectives: This study aims to characterize factors associated with STIs in a population of HIV-positive migrants living in Portugal. Methodology: This is a cross-sectional observational study of 265 newly diagnosed HIV-1 positive migrants, who were defined as individuals born outside Portugal. This group of people were part of the BESTHOPE study that was developed in 17 Portuguese hospitals between September 2014 and December 2019, and included information collected through sociodemographic and behavioral questionnaires filled in by the migrant patients, clinical questionnaires filled in by the clinicians and HIV-1 genomic sequences generated through resistance testing (Sanger sequencing). A multivariable statistical analysis was used to analyze the association between sociodemographic characteristics, sexual behaviors, HIV testing and sexual infections. Results: Most HIV-1 positive individuals included in the study were men (66.8%) and aged between 25 and 44 years old (59.9%). Men had a higher proportion of STIs when compared to women (40.4% vs. 14.0%) and the majority of men reported homosexual contacts (52.0%). Most men reported having had two or more occasional sexual partners in the previous year (88.8%) and 50.9% reported always using condoms with occasional partners, while 13.2% never used it. For regular partners, only 29.5% of the women reported using condoms, compared to 47.3% of men. Other risk behaviors for acquiring HIV, such as tattooing and performing invasive medical procedures, were more prevalent in men (38.0% and 46.2%, respectively), when compared to women (30.4% and 45.1% respectively) and 4.7% of men reported having already shared injectable materials, with no data for comparison in the case for women. Additionally, 23.9% of women reported having had a blood transfusion while only 10.3% of men reported having had this medical procedure. Meanwhile, 30.9% of the individuals reported having been diagnosed with some type of STI in the last 12 months. In addition, 43.3% of individuals that answered a question about hepatitis reported to be infected with hepatitis B, while 13.0% reported having hepatitis C infection. According to the multivariable analysis, the only transmission route was significantly associated with reports of previous STI infection: men who have sex with men (MSM) were 70% more likely to have been diagnosed with an STI in the past 12 months compared to the heterosexual route. Conclusion: HIV-1 infected men were more likely to report previous STIs than women. On the other hand, most migrant women had a regular sexual partner and never or only sometimes used condoms. This somewhat discrepant findings suggest that gender inequalities may make women unable to negotiate safe sexual practices, resulting in increased susceptibility to infection. However, since migrant women report less STIs, we cannot exclude that these STIs may remain undiagnosed. The implementation of safer sex awareness campaigns for condom use and screening for STIs in women is crucial. On the other hand, health education campaigns for STI knowledge need to be implemented for both MSM and women and their partners.