Browsing by Author "Mansinho, K"
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- Coreceptor Usage by HIV-1 and HIV-2 Primary Isolates: The Relevance of CCR8 Chemokine Receptor as an Alternative CoreceptorPublication . Calado, M; Matoso, P; Santos-Costa, Q; Espirito-Santo, M; Machado, J; Rosado, L; Antunes, K; Mansinho, K; Lopes, MM; Maltez, F; Santos-Ferreira, MO; Azevedo-Pereira, JMThe human immunodeficiency virus replication cycle begins by sequential interactions between viral envelope glycoproteins with CD4 molecule and a member of the seven-transmembrane, G-protein-coupled, receptors' family (coreceptor). In this report we focused on the contribution of CCR8 as alternative coreceptor for HIV-1 and HIV-2 isolates. We found that this coreceptor was efficiently used not only by HIV-2 but particularly by HIV-1 isolates. We demonstrate that CXCR4 usage, either alone or together with CCR5 and/or CCR8, was more frequently observed in HIV-1 than in HIV-2 isolates. Directly related to this is the finding that the non-usage of CXCR4 is significantly more common in HIV-2 isolates; both features could be associated with the slower disease progression generally observed in HIV-2 infected patients. The ability of some viral isolates to use alternative coreceptors besides CCR5 and CXCR4 could further impact on the efficacy of entry inhibitor therapy and possibly also in HIV pathogenesis.
- HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019Publication . Pingarilho, M; Pimentel, V; Miranda, M; Silva, AR; Diniz, A; Ascenção, B; Piñeiro, C; Koch, C; Rodrigues, C; Caldas, C; Morais, C; Faria, D; Gomes da Silva, E; Teófilo, E; Monteiro, F; Roxo, F; Maltez, F; Rodrigues, F; Gaião, G; Ramos, H; Costa, I; Germano, I; Simões, J; Oliveira, J; Ferreira, J; Poças, J; Saraiva da Cunha, J; Soares, J; Henriques, J; Mansinho, K; Pedro, L; Aleixo, MJ; Gonçalves, MaJ; Manata, MJ; Mouro, M; Serrado, M; Caixeiro, M; Marques, N; Costa, O; Pacheco, P; Proença, P; Rodrigues, P; Pinho, R; Tavares, R; Correia de Abreu, R; Côrte-Real, R; Serrão, R; Sarmento e Castro, R; Nunes, S; Faria, T; Baptista, T; Martins, MR; Gomes, P; Mendão, L; Simões, D; Abecasis, AObjective: 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.
- Micoses Sistémicas Oportunistas. Manifestações Clínicas, Diagnóstico e TratamentoPublication . Peres, S; Alfaiate, D; Aldir, I; Fernandes, C; Vieira, R; Cardoso, J; Mansinho, KA incidência das micoses invasivas oportunistas sofreu um aumento substancial nas últimas décadas, devido ao aumento do número de doentes em risco. A Candida albicans, o Aspergillus spp. e o Cryptococcus neoformans estão entre os agentes mais frequentemente implicados, embora espécies de Candida não-albicans, Zygomycetes e Fusarium spp. se tenham tornado fungos emergentes. A Candida é o principal agente causador de infecções oportunistas, em todo o mundo, sendo a espécie C. albicans a mais frequente. A candidase invasiva inclui a candidemia, a candidase disseminada, a endocardite, a meningite e a endoftalmite. O Aspergillus fumigatus é o principal fungo do género Aspergillus responsável por micoses invasivas. As formas clínicas de aspergilose invasiva incluem a aspergilose pulmonar, a rinosinusite invasiva e a doença disseminada sistémica com envolvimento de diversos órgãos. Os Zygomycetes são uma classe de fungos que inclui a ordem dos Entomophthorales e a dos Mucorales. A zigomicose é a infecção causada por estes últimos e manifesta-se por uma sinusite invasiva ou por doença disseminada rinocerebral, pulmonar, gastrintestinal ou cutânea. O Cryptococcus neoformans é a principal espécie do género Cryptococcus. A criptococose pulmonar resulta da inalação fúngica, que pode depois progredir para doença disseminada e envolver diversos órgãos, com atingimento preferencial do SNC. Até recentemente as opções terapêuticas para o tratamento das micoses invasivas passavam primariamente pelo uso de anfotericina B e dos triazóis fluconazol e itraconazol. Os avanços recentes no tratamento das infecções fúngicas com a introdução de novas gerações de fármacos das classes conhecidas e de novas classes de antifúngicos, particularmente variconazole, posaconazole e equinocandinas permitiu expandir as opções terapêuticas para os doentes.
- Non-AIDS-Related Comorbidities in People Living with HIV-1 Aged 50 Years and Older: The AGING POSITIVE StudyPublication . Serrão, R; Piñero, C; Velez, J; Coutinho, D; Maltez, F; Lino, S; Sarmento E Castro, R; Tavares, AP; Pacheco, P; Lopes, MJ; Mansinho, K; Miranda, AC; Neves, I; Correia de Abreu, R; Almeida, J; Pássaro, LObjective: To characterize the profile of non-AIDS-related comorbidities (NARC) in the older HIV-1-infected population and to explore the factors associated with multiple NARC. Methods: This was a multicentre, cross-sectional study including HIV-1-infected patients aged ≥50 years, who were virologically suppressed and had been on a stable antiretroviral therapy (ART) regimen for at least 6 months. A multiple regression model explored the association between demographic and clinical variables and the number of NARC. Results: Overall, 401 patients were enrolled. The mean age of the patients was 59.3 years and 72.6% were male. The mean duration of HIV-1 infection was 12.0 years and the median exposure to ART was 10.0 years. The mean number of NARC was 2.1, and 34.7% of patients had three or more NARC. Hypercholesterolemia was the most frequent NARC (60.8%), followed by arterial hypertension (39.7%) and chronic depression/anxiety (23.9%). Arterial hypertension and diabetes mellitus were the most frequently treated NARC (95.6% and 92.6% of cases, respectively). The linear regression analysis showed a positive relationship between age and NARC (B=0.032, 95% confidence interval 0.015-0.049; p=0.0003) and between the duration of HIV-1 infection and NARC (B=0.039, 95% confidence interval 0.017-0.059; p=0.0005). Conclusions: A high prevalence of NARC was found, the most common being metabolic, cardiovascular, and psychological conditions. NARC rates were similar to those reported for the general population, suggesting a larger societal problem beyond HIV infection. A multidisciplinary approach is essential to reduce the burden of complex multi-morbid conditions in the HIV-1-infected population.
- Normas de Actuação após Exposição Acidental a Produtos Biológicos Potencialmente InfectantesPublication . Borges, A; Guerreiro, C; Paredes, P; Nabais, H; Mansinho, KOs autores apresentam as normas de actuação pós-exposição acidental a produtos biológicos (sangue ou fluídos) potencialmente infectados (com destaque para o VIH, AgHbS e VHC). No caso concreto de exposição ao VIH, a decisão para a recomendação da profilaxia pós-exposição deve ser tomada tendo em conta a natureza da exposição (ex: agulhas ou fluídos potencialmente infectados, em contacto com as mucosas) bem como a quantidade de sangue ou fluído envolvida na exposição. Atendendo ao aumento das resistências a um ou mais dos fármacos anti-retrovíricos recomendados na profilaxia pós-exposição (PPE), em Maio de 1997, um grupo de especialistas do CDC reviu as normas de PPE e aprovou novos esquemas terapêuticos que incluem os Inibidores das Proteases (Indinavir e Nelfinavir). Desta forma, para além do esquema básico de 4 semanas com dois fármacos (zidovudina e lamivudina) utilizado na maior parte dos casos de PPE, poder-se-á considerar, nos casos de alto risco de transmissão da infecção VIH ou suspeita de resistência a um ou mais anti-retrovíricos do esquema básico, a inclusão de um inibidor da protease. Apresenta-se um algoritmo que deverá servir de guia aos clínicos quando confrontados com a decisão de considerar a PPE aos trabalhadores de saúde, após exposição acidental a produtos potencialmente contaminados.
- Risco Cardiovascular em Doentes com Infecção por Vírus da Imunodeficiência HumanaPublication . Raimundo, P; Miranda, A; Ribeiro, J; Mansinho, KO aumento do risco cardiovascular é considerada uma importante complicação da infecção Infecção por Vírus da Imunodeficiência Humana (VIH) e da terapêutica anti-retroviral (TARV). À disfunção endotelial característica do processo inflamatório crónico desencadeado pela infecção retroviral, associa-se a disfunção metabólica induzida pela terapêutica, predispondo, em conjunto, para a aterogénese precoce. O reconhecimento deste aumento de risco cardiovascular permite-nos elaborar estratégias de prevenção e optimização terapêutica que passam pelo uso criterioso de hipolipemiantes e modificação da TARV, consoante a avaliação do risco cardiovascular global de cada doente.
- Sociodemographic, Clinical, and Behavioral Factors Associated With Sexual Transmitted Infection Among HIV-1 Positive Migrants in Portugal: Are There Differences Between Sexes?Publication . Miranda, M; Pimentel, V; Graça, J; Seabra, S; Sebastião, C; Diniz, A; Faria, D; Teófilo, E; Roxo, F; Maltez, F; Germano, I; Oliveira, J; Ferreira, J; Poças, J; Mansinho, K; Mendão, L; Gonçalves, MJ; Mouro, M; Marques, N; Pacheco, P; Proença, P; Tavares, R; Correia de Abreu, R; Serrão, R; Faria, T; O. Martins, MR; Gomes, P; Abecasis, A; Pingarilho, MIntroduction: 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.
- The Association Between Hepatitis B Virus Infection and Nonliver Malignancies in Persons Living with HIV: Results from the EuroSIDA StudyPublication . Mocroft, A; Miro, J; Wandeler, G; Llibre, J; Boyd, A; van Bremen, K; Beniowski, M; Mikhalik, J; Cavassini, M; Maltez, F; Duvivier, C; Uberti Foppa, C; Knysz, B; Bakowska, E; Kuzovatova, E; Domingo, P; Zagalo, A; Viard, JP; Degen, O; Milinkovic, A; Benfield, T; Peters, L; Harxhi, A; Losso, M; Kundro, M; Schmied, B; Zangerle, R; Karpov, I; Vassilenko, A; Mitsura, V; Paduto, D; Clumeck, N; De Wit, S; Delforge, M; Florence, E; Vandekerckhove, L.; Hadziosmanovic, V; Begovac, J; Machala, L; Sedlacek, D; Kronborg, G; Gerstoft, J; Katzenstein, T; Pedersen, C; Johansen, I; Ostergaard, L; Wiese, L; Moller, N; Nielsen, L; Zilmer, K; Smidt, J; Aho, I; Lacombe, K; Pradier, C; Fontas, E; Rockstroh, J; Behrens, G; Hoffmann, C; Stellbrink, H; Stefan, C; Bogner, J; Fätkenheuer, G; Chkhartishvili, N; Sambatakou, H; Adamis, G; Paissios, N; Szlávik, J; Gottfredsson, M; Devitt, E; Tau, L; Turner, D; Burke, M; Shahar, E; Wattad, L; Elinav, H; Haouzi, M; Elbirt, D; D’Arminio Monforte, A; Esposito, R; Mazeu, I; Mussini, C; Mazzotta, F; Gabbuti, A; Lazzarin, A; Castagna, A; Gianotti, N; Galli, M; Ridolfo, A; Uzdaviniene, V; Matulionyte, R; Staub, T; Hemmer, R; Dragas, S; Stevanovic, M; vd Valk, M; Trajanovska, J; Reikvam, D; Maeland, A; Bruun, J; Szetela, B; Inglot, M; Flisiak, R; Grzeszczuk, A; Parczewski, M; Maciejewska, K; Aksak‐Was, B; Mularska, E; Jablonowska, E; Kamerys, J; Wojcik, K; Mozer‐Lisewska, I; Rozplochowski, B; Mansinho, K; Radoi, R; Oprea, C; Gusev, D; Trofimova, T; Khromova, I; Borodulina, E; Ranin, J; Tomazic, J; Miró, J; Laguno, M; Martinez, E; Garcia, F; Blanco, J; Martinez‐Rebollar, M; Mallolas, J; Callau, P; Rojas, J; Inciarta, A; Moreno, S; del Campo, S; Clotet, B; Jou, A; Paredes, R; Puig, J; Santos, J; Gutierrez, M; Mateo, G; Sambeat, M; Laporte, J; Svedhem, V; Thalme, A; Sönnerborg, A; Brännström, J; Flamholc, L; Kusejko, K; Braun, D; Calmy, A; Furrer, H; Battegay, M; Schmid, P; Kuznetsova, A; Sluzhynska, M; Johnson, A; Simons, E; Edwards, S; Phillips, A; Johnson, M; Orkin, C; Winston, A; Clarke, A; Leen, C; Karpov, I; Losso, M; Lundgren, J; Rockstroh, J; Aho, I; Rasmussen, L; Svedhem, V; Pradier, C; Chkhartishvili, N; Matulionyte, R; Oprea, C; Kowalska, J; Begovac, J; Miró, J; Guaraldi, G; Paredes, R; Paredes, R; Larsen, J; Bojesen, A; Neesgaard, B; Jaschinski, N; Fursa, O; Sather, M; Raben, D; Hansen, E; Kristensen, D; Fischer, A; Jensen, S; Elsing., T; Phillips, A; Reekie, J; Cozzi‐Lepri, A; Amele, S; Pelchen‐Matthews, A; Roen, A; Tusch, E; Bannister., WObjectives: The aim of this study was to assess the impact of hepatitis B virus (HBV) infection on non-liver malignancies in people living with HIV (PLWH). Methods: All persons aged ≥ 18 years with known hepatitis B virus (HBV) surface antigen (HBsAg) status after the latest of 1 January 2001 and enrolment in the EuroSIDA cohort (baseline) were included in the study; persons were categorized as HBV positive or negative using the latest HBsAg test and followed to their first diagnosis of nonliver malignancy or their last visit. Results: Of 17 485 PLWH included in the study, 1269 (7.2%) were HBV positive at baseline. During 151 766 person-years of follow-up (PYFU), there were 1298 nonliver malignancies, 1199 in those currently HBV negative [incidence rate (IR) 8.42/1000 PYFU; 95% confidence interval (CI) 7.94-8.90/1000 PYFU] and 99 in those HBV positive (IR 10.54/1000 PYFU; 95% CI 8.47-12.62/1000 PYFU). After adjustment for baseline confounders, there was a significantly increased incidence of nonliver malignancies in HBV-positive versus HBV-negative individuals [adjusted incidence rate ratio (aIRR) 1.23; 95% CI 1.00-1.51]. Compared to HBV-negative individuals, HBsAg-positive/HBV-DNA-positive individuals had significantly increased incidences of nonliver malignancies (aIRR 1.37; 95% CI 1.00-1.89) and NHL (aIRR 2.57; 95% CI 1.16-5.68). There was no significant association between HBV and lung or anal cancer. Conclusions: We found increased rates of nonliver malignancies in HBsAg-positive participants, the increases being most pronounced in those who were HBV DNA positive and for NHL. If confirmed, these results may have implications for increased cancer screening in HIV-positive subjects with chronic HBV infection.
- The Demise of Multidrug-Resistant HIV-1: the National Time Trend in PortugalPublication . Vercauteren, J; Theys, K; Carvalho, AP; Valadas, E; Duque, LM; Teófilo, E; Faria, T; Faria, D; Vera, J; Aguas, MJ; Peres, S; Mansinho, K; Vandamme, AM; Camacho, ROBJECTIVES: Despite a decreasing mortality and morbidity in treated HIV-1 patients, highly active antiretroviral treatment (HAART) can still fail due to the development of drug resistance. Especially, multidrug-resistant viruses pose a threat to efficient therapy. We studied the changing prevalence of multidrug resistance (MDR) over time in a cohort of HIV-1-infected patients in Portugal. PATIENTS AND METHODS: We used data of 8065 HIV-1-infected patients followed from July 2001 up to April 2012 in 22 hospitals located in Portugal. MDR at a specific date of sampling was defined as no more than one fully active drug (excluding integrase and entry inhibitors) at that time authorized by the Portuguese National Authority of Medicines and Health Products (INFARMED), as interpreted with the Rega algorithm version 8.0.2. A generalized linear mixed model was used to study the time trend of the prevalence of MDR. RESULTS: We observed a statistically significant decrease in the prevalence of MDR over the last decade, from 6.9% (95% CI: 5.7-8.4) in 2001-03, 6.0% (95% CI: 4.9-7.2) in 2003-05, 3.7% (95% CI: 2.8-4.8) in 2005-07 and 1.6% (95% CI: 1.1-2.2) in 2007-09 down to 0.6% (95% CI: 0.3-0.9) in 2009-12 [OR=0.80 (95% CI: 0.75-0.86); P<0.001]. In July 2011 the last new case of MDR was seen. CONCLUSIONS: The prevalence of multidrug-resistant HIV-1 is decreasing over time in Portugal, reflecting the increasing efficiency of HAART and the availability of new drugs. Therefore, in designing a new drug, safety and practical aspects, e.g. less toxicity and ease of use, may need more attention than focusing mainly on efficacy against resistant strains.