Percorrer por autor "Mansinho, Kamal"
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- Antibody response against selected epitopes in the HIV-1 envelope gp41 ectodomain contributes to reduce viral burden in HIV-1 infected patientsPublication . Marcelino, Rute; Gramacho, Filipa; Martin, Francisco; Brogueira, Pedro; Janeiro, Nuno; Afonso, Cláudia; Badura, Robert; Valadas, Emília; Mansinho, Kamal; Caldeira, Luís; Taveira, Nuno; Marcelino, José M.The ectodomain of gp41 is the target of potent binding and neutralizing antibodies (NAbs) and is being explored in new strategies for antibody-based HIV vaccines. Previous studies have suggested that the W164A-3S (3S) and EC26-2A4 (EC26) peptides located in the gp41 ectodomain may be potential HIV vaccine candidates. We assessed 3S- and EC26-specific binding antibody responses and related neutralizing activity in a large panel of chronic HIV-1-infected Portuguese individuals on ART. A similar proportion of participants had antibodies binding to 3S (9.6%) and EC26 (9.9%) peptides but the level of reactivity against 3S was significantly higher compared to EC26, except in the rare patients with double peptide reactivity. The higher antigenicity of 3S was unrelated with disease stage, as assessed by CD4+ T cell counts, but it was directly related with plasma viral load. Most patients that were tested (89.9%, N = 268) showed tier 1 neutralizing activity, the potency being inversely associated with plasma viral load. In the subset of patients that were tested for neutralization of tier 2 isolates, neutralization breadth was inversely correlated with plasma viral load and directly correlated with CD4+ T cell counts. These results are consistent with a role for neutralizing antibodies in controlling viral replication and preventing the decline of CD4+ T lymphocytes. Importantly, in patients with 3S-specific antibodies, neutralizing titers were inversely correlated with viral RNA levels and proviral DNA levels. Moreover, patients with 3S and/or EC26-specific antibodies showed a 1.9-fold higher tier 2 neutralization score than patients without antibodies suggesting that 3S and/or EC26-specific antibodies contribute to neutralization breadth and potency in HIV-1 infected patients. Overall, these results suggest that antibodies targeting the S3 and EC26 epitopes may contribute to reduce viral burden and provide further support for the inclusion of 3S and EC26 epitopes in HIV-1 vaccine candidates.
- Characterization of NS5A and NS5B resistance-associated substitutions from genotype 1 Hepatitis C Virus infected patients in a Portuguese cohortPublication . Brandão, Ruben; Marcelino, Rute; Gonçalves, Fátima; Diogo, Isabel; Carvalho, Ana; Cabanas, Joaquim; Costa, Inês; Brogueira, Pedro; Ventura, Fernando; Miranda, Ana; Mansinho, Kamal; Gomes, PerpétuaThis study is focused on the prevalent NS5 coding region resistance-associated substitutions (RASs) in DAA-naive genotype (GT)1 HCV-infected patients and their potential impact on success rates. Plasma RNA from 81 GT1 HCV-infected patients was extracted prior to an in-house nested RT-PCR of the NS5 coding region, which is followed by Sanger population sequencing. NS5A RASs were present in 28.4% (23/81) of all GT1-infected patients with 9.9% (8/81) having the Y93C/H mutation. NS5B RASs showed a prevalence of 14.8% (12/81) and were only detected in GT1b. Overall 38.3% (31/81) of all GT1 HCV-infected patients presented baseline RASs. The obtained data supports the usefulness of resistance testing prior to treatment since a statistically significant association was found between treatment failure and the baseline presence of specific NS5 RASs known as Y93C/H (p = 0.04).
- 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.
- 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.
- Management of HIV-2 resistance to antiretroviral therapy in a HIV-1/HIV-2/HBV co-infected patientPublication . Cardoso, Margarida; Vasconcelos, Joana; Baptista, Teresa; Diogo, Isabel; Gonçalves, Fátima; Mansinho, Kamal; Gomes, PerpétuaBackground: The current standard of care is to start antiretroviral therapy in all patients diagnosed with HIV-1, as for HIV-2 current DHHS guideline suggests ART for HIV-2 as soon as diagnosis is established, although this practice is not universal, for instance, in Portugal there are specific criteria to start treatment. Case presentation: We present a case of a man, chronically infected with HIV-1, HIV-2 and hepatitis B virus who developed resistance to HIV-2 while maintaining HIV-1 under control. 6 years after starting antiretroviral therapy he had his first virologic failure. We performed HIV-2 resistance tests that revealed high-grade resistance to all nucleoside reverse-transcriptase inhibitors except tenofovir and to all protease inhibitors except darunavir. After a decade of permanent poor adherence to therapy he developed resistance to both tenofovir and darunavir. We put together a new regiment with tenofovir alafenamide + emtricitabine + dolutegravir + maraviroc and nowadays he is with undetectable HIV-1 and HIV-2 viral loads. Conclusions: This shows the importance of having access to HIV-2 viral load determination and HIV-2 resistance testing.
- A retrospective observational study of low-level viraemia and its immunological and virological significance: which outcome to expectPublication . Silva, Joana; Pereira, Karen; Rijo, João; Alberto, Teresa; Cabanas, Joaquim; Gomes, Perpétua; Farinha, Helena; Mansinho, KamalAbstracts of the HIV Drug Therapy Glasgow Congress 2014.
- 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.
- 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; Correia de Abreu, Ricardo; Serrão, Rosário; Faria, Telo; O. Martins, M. Rosário; 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.