Browsing by Author "Germano, I"
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- Chronic Hepatitis C Treatment in HIV Co-Infection in Portugal: Results from a Cohort OF 2133 Patients Presented by GEPCOI (Portuguese Coinfection Study Group)Publication . Miranda, AC; Mendez, J; Serrão, R; Vale, F; Manata, MJ; Pinto, S; Gomes, A; Valente, C; Pacheco, P; Pazos, R; Pereira, R; Martins, A; Germano, I; Rocha, S; Reis, AP; Sarmento-Castro, RDirect-acting antiviral drugs (DAAs) have recently changed the paradigm of hepatitis C therapy, significantly improving treatment response rates, patient life expectancy and quality of life. In Portugal, sofosbuvir (SOF) and SOF/ledipasvir (SOF/LDV) were fully reimbursed by the National Health System since early 2015 and generalized use of interferon-free DAA based regimens became current practice. During 2016, the remaining DAAs were sequentially added and covered by the same health access policy. The Portuguese Study Group of Hepatitis and HIV Co-infection (GEPCOI) collected data from 15 clinical centres in Portugal, pertaining to the HCV treatment experience with DAA regimens. A cohort of 2133 patients was analysed, representing one of the largest DAA treated HCV/HIV co-infected individuals. The global sustained virologic response (SVR) achieved was 95% in this real-life cohort setting. Linear regression analysis showed significant differences in treatment response rates when using SOF plus ribavirin (RBV) combination in genotype 2 or 3 infected individuals (P < .002) and in those with liver cirrhosis (P < .002). These findings corroborate that early treatment is mandatory in HIV/HCV co-infected patients, as response rates may be negatively influenced by higher fibrosis stages and suboptimal DAA regimens. The current national Portuguese health policy should continue to promote wider treatment access and individualized therapy strategies, aiming at the elimination of HCV infection in this high-risk co-infected population.
- Efavirenz Concentrations in HIV-Infected Patients With and Without Viral HepatitisPublication . Pereira, SA; Caixas, U; Branco, T; Germano, I; Lampreia, F; Papoila, AL; Monteiro, EAIMS: Data on efavirenz in HIV/viral hepatitis co-infected patients is non-consensual, probably due to liver function heterogeneity in the patients included. METHODS: A case control study was performed on 27 HIV-infected patients, with controlled and homogenous markers of hepatic function, either mono-infected or co-infected with HBV/HCV, to ascertain the influence of viral hepatitis on efavirenz concentrations over a 2-year follow-up period. RESULTS: No differences were found in efavirenz concentrations between groups both during and at the end of the follow-up period: control (2.43 +/- 1.91 mg l(-1)) vs. co-infected individuals (2.37 +/- 0.37 mg l(-1)). CONCLUSION: It was concluded that HBV/HCV infections in themselves do not predispose to an overexposure to efavirenz.
- Effect of Efavirenz on High-Density Lipoprotein Antioxidant Properties in HIV-Infected PatientsPublication . Pereira, SA; Batuca, JR; Caixas, U; Branco, T; Delgado-Alves, J; Germano, I; Lampreia, F; Monteiro, ECWHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * In previous work, we showed a long-term and concentration-dependent beneficial effect of the non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) on high-density lipoproteins (HDL) in human immunodeficiency virus (HIV)-infected patients. * Furthermore, it has been suggested that instead of the current practice of only measuring HDL-chelesterol values, the evaluation of HDL function, namely its antioxidant properties, might be an improved tool for identifying subjects at increased risk for cardiovascular events. * Paraoxonase-1 (PON-1) is an enzyme associated with HDL that is responsible for HDL antioxidant function. WHAT THIS STUDY ADDS: * In the present work, we studied the effect of EFV on the activity of PON-1 and showed, for the first time, that EFV-based antiretroviral therapy is associated with a better antioxidant function, i.e. with a higher PON-1 activity. AIMS: A long-term and concentration-dependent beneficial effect of efavirenz (EFV) on cholesterol associated with high-density lipoprotein (HDL-c) in human immunodeficiency virus (HIV)-infected patients has been documented. Furthermore, it has been suggested that, instead of the current practice of only measuring HDL-c values, the evaluation of HDL quality might be an improved tool for identifying subjects at increased risk of cardiovascular events. Paraoxonase-1 (PON-1) is an enzyme associated with HDL that is involved in the onset of cardiovascular disease and responsible for HDL antioxidant function. The aim of the present study was to investigate the effect of EFV on the circulating activity of PON-1 in HIV-infected patients. METHODS: The patients included were adults with a documented HIV-1 infection, nontreated or treated with antiretroviral regimens including EFV 600 mg once daily as first therapeutic regimen for at least 3 months. The influence of treatment with EFV, HDL-c and CD4 cell count on PON-1 activity was analysed. RESULTS: HIV-infected White patients treated with EFV had higher PON-1 activity [77.35 U l(-1) (65.66, 89.04)] (P < 0.05) and higher PON-1 activity : HDL-c ratio [1.88 (1.49, 2.28)] (P < 0.01) than untreated patients. PON-1 activity was higher in Black patients (P < 0.001) and in patients with a CD4 cell count >500 cells ml(-1) (P= 0.0120). CONCLUSIONS: EFV-based antiretroviral regimens are associated with HDL particles with a better antioxidant function, i.e. with a higher PON-1 activity. The PON-1 activity of Black patients is higher than that found in Whites regardless of treatment. Ethnicity should be taken into consideration when studying drug effects on PON-1 activity.
- Hematomas Cerebelosos em Doente com Mixoma AuricularPublication . Marcão, I; Teixeira, H; Germano, I; Bandeira Costa, J; Gonçalves, C; Magalhães, M; Farrajota, FApresenta-se um caso clínico de mixoma auricular, numa mulher de 69 anos, que teve como manifestação inaugural síndroma cerebeloso, causado por enfartes isquémicos da circulação posterior. O Ecocardiograma transtorácico bidimensional permitiu formular o diagnóstico de mixoma da aurícula esquerda. Ao 7° mês pós remoção cirúrgica do tumor cardíaco houve agravamento do síndroma cerebeloso e instalação de quadro de hipertensão intracraneana. A TAC-CE revelou múltiplos hematomas dos hemisférios cerebelosos e do vérmix e hidrocefalia triventricular activa. Estas complicações neurológicas tardias permitiram suspeitar e discutir hipóteses diagnósticas. Os mixomas cardíacos são raros e a sua apresentação como manifestação neurológica ocorre em 20-25% dos casos. As complicações neurológicas tardias do mixoma são ainda mais raras, encontrando-se alguns casos descritos a nível mundial.
- 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.
- HIV-2 Integrase Polymorphisms and Longitudinal Genotypic Analysis of HIV-2 Infected Patients Failing a Raltegravir-Containing RegimenPublication . Cavaco-Silva, J; Abecasis, A; Miranda, AC; Poças, J; Narciso, J; Águas, MJ; Maltez, F; Almeida, I; Germano, I; Diniz, A; Gonçalves, MF; Gomes, P; Cunha, C; Camacho, RJTo characterize the HIV-2 integrase gene polymorphisms and the pathways to resistance of HIV-2 patients failing a raltegravir-containing regimen, we studied 63 integrase strand transfer inhibitors (INSTI)-naïve patients, and 10 heavily pretreated patients exhibiting virological failure while receiving a salvage raltegravir-containing regimen. All patients were infected by HIV-2 group A. 61.4% of the integrase residues were conserved, including the catalytic motif residues. No INSTI-major resistance mutations were detected in the virus population from naïve patients, but two amino acids that are secondary resistance mutations to INSTIs in HIV-1 were observed. The 10 raltegravir-experienced patients exhibited resistance mutations via three main genetic pathways: N155H, Q148R, and eventually E92Q - T97A. The 155 pathway was preferentially used (7/10 patients). Other mutations associated to raltegravir resistance in HIV-1 were also observed in our HIV-2 population (V151I and D232N), along with several novel mutations previously unreported. Data retrieved from this study should help build a more robust HIV-2-specific algorithm for the genotypic interpretation of raltegravir resistance, and contribute to improve the clinical monitoring of HIV-2-infected patients.
- HIV-Associated Facial Lipodystrophy: Experience of a Tertiary Referral Center With Fat and Dermis-Fat Compound Graft TransferPublication . Martins de Carvalho, F; Casal, D; Bexiga, J; Sousa, J; Martins, J; Teófilo, E; Maltez, F; Germano, I; Videira e Castro, JObjectives: HIV-associated lipodystrophy is a common comorbidity in HIV-infected patients, having a profound impact on every aspect of patients' lives, particularly when involving the face. Hence, it is of the utmost importance to evaluate the result of any potential therapies that may help solve HIV-associated facial lipodystrophy. The aim of this article was to evaluate the outcome of patients undergoing facial lipodystrophy correction surgery within our institution. Methods: A retrospective analysis of the clinical charts and iconographic information of patients regarding demographics, morphologic changes, surgical option, postoperative complications, results, and patient satisfaction assessed by a 1- to 10-point scale and by the Assessment of Body Change and Distress questionnaire. Results: Twenty-three patients were operated on from March 2011 to April 2015. Seventy-five percent of cases were treated with fat graft injection, whereas dermis-fat grafts were applied in 25% of patients. The former had their fat harvested more commonly from the abdomen, whereas in the latter case, the graft was harvested mostly from the inner aspect of arms. The mean volume of fat injected on each side of the face was 28.5 ± 22.7 mL. On a scale from 1 to 10, mean patient satisfaction was 7.7 ± 2.8. The Assessment of Body Change and Distress questionnaire revealed statistically significant improvements. Complications occurred in 25% of cases, the most frequent being significant reabsorption. No major complications occurred. Conclusions: Treatment of HIV-associated facial lipodystrophy with autologous fat or dermis-fat compound graft is a safe procedure with long-lasting results and unquestionable aesthetic and social benefits.
- Linfoma Primário das Cavidades em Doente com Infecção VIHPublication . Gouveia, S; Castro, M; Correia, R; Germano, I; Farrajota, FO linfoma primário das cavidades é um subtipo de linfoma não-Hodgkin (LNH), de ocorrência rara, prognóstico muito reservado, mais frequentemente descrito em indivíduos imunodeprimidos, em particular no contexto de infecção pelo vírus da imunodeficiência humana (VIH), no qual as células malignas proliferam exclusivamente nas cavidades serosas e que está associado ao vírus herpes humano tipo 8 (VHH8). Os autores apresentam o caso de um doente com infecção VIH, internado por febre e queixas constitucionais e que desenvolveu, enquanto decorria estudo etiológico da síndrome febril, ascite volumosa e, ainda, derrame pleural direito e derrame pericárdico. O líquido ascítico mostrou a presença de células grandes linfóides com fenótipo não B e não T. Não foram evidenciadas massas tumorais, linfadenopatias ou envolvimento da medula óssea. O doente morreu 41 dias após o diagnóstico, sem ter iniciado quimioterapia. Ainda que não tenha sido possível a demonstração de infecção pelo VHH-8 nas células linfóides, os dados clínicos, citológicos e imunofenotípicos apontam para um diagnóstico altamente provável de linfoma primário das cavidades.
- Long-Term and Concentration-Dependent Beneficial Effect of Efavirenz on HDL-Cholesterol in HIV-Infected PatientsPublication . Pereira, SA; Branco, T; Côrte-Real, R; Germano, I; Lampreia, F; Caixas, U; Monteiro, EAIMS: To investigate the long-term effects of efavirenz on cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL-C) and triglycerides (TG). METHODS: Thirty-four HIV-infected patients who commenced efavirenz therapy were monitored for 36 months. RESULTS: In patients with baseline HDL-C<40 mg.dL-1 an increase in HDL-C from 31+/-1 mg.dL-1 to 44+/-2 mg.dL-1 (95% confidence interval 5.9, 21.9, P<0.01) was observed and remained throughout the follow-up period. Median efavirenz plasma concentration was 1.98 mg.L-1 and a direct correlation between percentage of HDL-C variation or TC/HDL-C ratio and efavirenz plasma concentrations was found. CONCLUSIONS: There is evidence of a long-term and concentration-dependent beneficial effect of efavirenz on HDL-C in HIV-infected patients.
- Long-Term Maraviroc Use As Salvage Therapy in HIV-2 InfectionPublication . Caixas, U; Ferreira, J; Marinho, A; Faustino, I; Grilo, N; Lampreia, F; Germano, I; Monteiro, E; Pereira, S