Percorrer por autor "Pimentel, Victor"
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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.
- 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.
- HIV-1 diversity and pre-treatment drug resistance in the era of integrase inhibitor among newly diagnosed ART-naïve adult patients in Luanda, AngolaPublication . Sebastião, Cruz S.; Abecasis, Ana B.; Jandondo, Domingos; Sebastião, Joana M. K.; Vigário, João; Comandante, Felícia; Pingarilho, Marta; Pocongo, Bárbara; Cassinela, Edson; Gonçalves, Fátima; Gomes, Perpétua; Giovanetti, Marta; Francisco, Ngiambudulu M.; Sacomboio, Euclides; Brito, Miguel; Vasconcelos, Jocelyne Neto de; Morais, Joana; Pimentel, VictorThe surveillance of drug resistance in the HIV-1 naïve population remains critical to optimizing the effectiveness of antiretroviral therapy (ART), mainly in the era of integrase strand transfer inhibitor (INSTI) regimens. Currently, there is no data regarding resistance to INSTI in Angola since Dolutegravir-DTG was included in the first-line ART regimen. Herein, we investigated the HIV-1 genetic diversity and pretreatment drug resistance (PDR) profile against nucleoside/tide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and INSTIs, using a next-generation sequencing (NGS) approach with MinION, established to track and survey DRMs in Angola. This was a cross-sectional study comprising 48 newly HIV-diagnosed patients from Luanda, Angola, screened between March 2022 and May 2023. PR, RT, and IN fragments were sequenced for drug resistance and molecular transmission cluster analysis. A total of 45 out of the 48 plasma samples were successfully sequenced. Of these, 10/45 (22.2%) presented PDR to PIs/NRTIs/NNRTIs. Major mutations for NRTIs (2.2%), NNRTIs (20%), PIs (2.2%), and accessory mutations against INSTIs (13.3%) were detected. No major mutations against INSTIs were detected. M41L (2%) and I85V (2%) mutations were detected for NRTI and PI, respectively. K103N (7%), Y181C (7%), and K101E (7%) mutations were frequently observed in NNRTI. The L74M (9%) accessory mutation was frequently observed in the INSTI class. HIV-1 pure subtypes C (33%), F1 (17%), G (15%), A1 (10%), H (6%), and D (4%), CRF01_AG (4%) were observed, while about 10% were recombinant strains. About 31% of detected HIV-1C sequences were in clusters, suggesting small-scale local transmission chains. No major mutations against integrase inhibitors were detected, supporting the continued use of INSTI in the country. Further studies assessing the HIV-1 epidemiology in the era of INSTI-based ART regimens are needed in Angola.
- HIV-1 late diagnosis : strategies to overcome the misclassification of individuals acutely infected with HIV-1 as individuals diagnosed latePublication . Miranda, Mafalda N. S.; Pimentel, Victor; Santos, André; Alemão, André; Gonçalves, Fátima; Cabanas, Joaquim; Costa, Inês; Diogo, Isabel; Fernandes, Sandra; Seabra, Sofia G.; Gomes, Perpétua; Pingarilho, Marta; Abecasis, Ana; on behalf of the Portuguese HIV-1 Resistance Study GroupObjectives: Late HIV diagnosis is associated with a higher impact on treatment outcomes and a potential for prolonged transmissibility of HIV-1 infection. The consensus definition for late HIV diagnosis is problematic. It was updated in 2022; however, this definition relies on information that might not be clinically available. This study aimed to assess late HIV diagnosis using alternative parameters, in addition to the definition of clusters of differentiation (CD4) cell count, namely, sequence ambiguity rate and estimated time of infection inferred through phylogenetic analysis. Methods: Clinical, socio-demographic, and genotypic information from 3668 antiretroviral therapy–naïve individuals living with HIV was retrieved from the REGA database. Individuals were classified according to three approaches: (i) CD4 cell count, (ii) sequence ambiguity rate, and (iii) phylogenetic reconstruction using TreeTime to estimate the time of most recent common ancestor (MRCA) as a proxy for time of infection. Results: Based on CD4 cell count, 53.8% of individuals had a late diagnosis and 46.2% had a non-late diagnosis. Based on sequence ambiguity rate, 57.8% had a chronic and 42.2% had a recent infection, and 86.4% had an estimated time of infection of more than 3 years, whereas 13.6% had less than 3 years. A total of 114 individuals were classified as diagnosed late by CD4 criteria and showed evidence of recent infection based on low ambiguity rates and MRCA estimates under 3 years. These individuals had significantly lower viral loads than those with true late diagnoses (median 61,358 vs 134,730 copies/ml; P <0.001). Overall, 41% of individuals were consistently classified across all three methods. Conclusions: The definition of late diagnosis remains a major challenge. Alternative and complementary methods, such as the use of viral loads, combined with some more clinical information, may improve the lack of baseline data.
- HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019Publication . Pingarilho, Marta; Pimentel, Victor; Miranda, Mafalda N. S.; Silva, Ana Rita; Diniz, António; Ascenção, Bianca Branco; Piñeiro, Carmela; Koch, Carmo; Rodrigues, Catarina; Caldas, Cátia; Morais, Célia; Faria, Domitília; da Silva, Elisabete Gomes; 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; da Cunha, José Saraiva; Soares, Jorge; Henriques, Júlia; 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; de Abreu, Ricardo Correia; Côrte-Real, Rita; Serrão, Rosário; Castro, Rui Sarmento e; Nunes, Sofia; Faria, Telo; Baptista, Teresa; Martins, Maria Rosário O.; Gomes, Perpétua; Mendão, Luís; Simões, Daniel; Abecasis, AnaObjective: To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks. Methods: Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses. Results: In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (p for-trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G. Conclusion: Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.
- HIV-1-transmitted drug resistance and transmission clusters in newly diagnosed patients in Portugal between 2014 and 2019Publication . Pingarilho, Marta; Pimentel, Victor; Miranda, Mafalda N. S.; Silva, Ana Rita; Diniz, António; Ascenção, Bianca Branco; 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; Henriques, Júlia; 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; Martins, Maria Rosário O.; Gomes, Perpétua; Mendão, Luís; Simões, Daniel; Abecasis, Ana; on behalf of the BESTHOPE Study GroupObjective: To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks. Methods: Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses. Results: In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (pfor–trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G. Conclusion: Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.