Infecciologia
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- One year of Lamivudine therapy for portuguese patients with chronic hepatitis B.Publication . Areias, J; Calinas, F; Porto, A; Carvalho, A; Freitas, D; Macedo, G; Noronha, R; Cotter, J; Meliço-Silvestre, A; Peixe, R; Pratas, J; Barrote, D; Teixeira, R; Augusto, F; Carrilho, I; Campante, F; Velosa, J; Carvalho, L; Duarte, M; Guerreiro, H; Pires, C; Silva, A; Cotrim, I; Guedes, F; Tomé, L; Marcelino, M; Gonçalves, C; Ferreira, E; Matos, L; Peixe, P; Esteves, J; Valente, T; Simões, C; Marinho, C; Jasmins, L; Vieira, M; Marinho, R; Matos, P; Estevans, J; Carrasquinho, J; Salsedo, G; Parada, P; Teixeira, COBJECTIVE: To further verify the efficacy and safety of locally manufactured lamivudine on patients with chronic hepatitis B (CHB). METHODS: 2200 patients with CHB were recruited and received lamivudine orally 100 mg once daily for 12 months. The efficacy assessments included virologic response rate (defined by the absence of serum HBV DNA, HBeAg loss and HBeAg/HBeAb seroconversion), percentage of patients with normalization of alanine aminotransferase (ALT). Meanwhile improvement of quality of life (QOL) measured by mos SF-36 QOL questionnaire and liver histology evaluation were conducted in some patients. The safety assessments included adverse events, serious adverse events and laboratory abnormalities. All 2200 patients received at least one dose of medication and were all included in the safety population. RESULTS: Ninety seven percent of patients (2137/2200) recruited were HBV DNA positive by dot blot (sensitivity GRT or equal to 1.0 pg/ml) at baseline. At the end of 12 months treatment, HBV DNA was undetectable in 80% patients (1538/1920) with HBV DNA positive before treatment. Among the 79%(1744/2200) of the patients recruited had positive HBV DNA accompanied abnormal ALT levels at baseline, 72% patients became ALT normal. And among the 84% (1843/2200) of the patients recruited were HBV DNA and HBeAg positive, anti-HBe negative, 16% (269/1650) patients achieved HBeAg/HBeAb seroconversion after 12 months of lamivudine treatment. The HBeAg/HBeAb seroconversion rate was positive correlation to the ALT level before treatment. A total of 304 patients completed the health-related QOL questionnaire. After 12 months treatment, lamivudine improved both their physical and mental health, especially for their mental health. 133 evaluable, paired liver biopsies were obtained for histological assessment, among whom 115 patients had abnormal ALT levels at baseline. Compared with pre-treatment most of their liver injury got alleviated (51.9%) or no further deterioration (36%), only 12% worsening. During the 12 months treatment, 9% patients withdrew from the study and 17% patients showed at least one adverse event, mild or moderate. There were no obvious difference between this study and the previously reported lamivudine Phase II or III study with regard to the kinds, incidence and severity of adverse events. CONCLUSION: The efficacy and safety profile of the locally manufactured lamivudine 100 mg tablets are similar with those of the previously reported available lamivudine tablets imported in treating Chinese chronic hepatitis B patients.
- A propósito de dois casos clínicos de linfoma de Burkitt do rim em doentes com infecção a VIHPublication . Gonçalves, L; Aparício, S; Costa, MM; Inchaustegui, L; Costa, C; Fiúza, T; Silva, S
- Síndrome de Ramsay-Hunt complicado con trombosis venosa cerebral como primera manifestación de infección por VIH-1Publication . Pazos-Añón, R; Machado-Costa, C; Abreu, JF
- Efavirenz concentrations in HIV-infected patients with and without viral hepatitisPublication . Pereira, S; Caixas, U; Branco, T; Germano, I; Lampreia, F; Papoila, A; 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.
- Consulta de adesão terapêuticaPublication . Costa, A; Jiménez, E; Correia, J
- Effect of efavirenz on high-density lipoprotein antioxidant properties in HIV-infected patientsPublication . Pereira, S; Batuca, J; Caixas, U; Branco, T; Delgado-Alves, J; Germano, I; Lampreia, F; Monteiro, EWHAT 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.
- Randomized comparison of renal effects, efficacy, and safety with once-daily abacavir/lamivudine versus tenofovir/emtricitabine, administered with efavirenz, in antiretroviral-naive, HIV-1-infected adults: 48-week results from the ASSERT studyPublication . Post, F; Moyle, G; Stellbrink, H; Domingo, P; Podzamczer, D; Fisher, M; Norden, A; Cavassini, M; Rieger, A; Khuong-Josses, MA; Branco, T; Pearce, H; Givens, N; Vavro, C; Lim, MBACKGROUND: Abacavir/lamivudine and tenofovir/emtricitabine fixed-dose combinations are commonly used first-line antiretroviral therapies, yet few studies have comprehensively compared their safety profiles. METHODS: Forty-eight-week data are presented from this multicenter, randomized, open-label study comparing the safety profiles of abacavir/lamivudine and tenofovir/emtricitabine, both administered with efavirenz, in HLA-B*5701-negative HIV-1-infected adults. RESULTS: Three hundred eighty-five subjects were enrolled in the study. The overall rate of withdrawal was high (28%). Changes in estimated glomerular filtration rate from baseline were similar between arms [difference 0.953 mL.min.1.73 m (95% confidence interval: -1.445 to 3.351), P = 0.435]. Urinary excretion of retinol-binding protein and beta-2 microglobulin increased significantly more in the tenofovir/emtricitabine arm (+50%; +24%) compared with the abacavir/lamivudine arm (no change; -47%) (P < 0.0001). A lower proportion achieved viral load <50 copies per milliliter in the abacavir/lamivudine arm (114 of 192, 59%) compared with the tenofovir/emtricitabine arm (137 of 193, 71%) [difference 11.6% (95% confidence interval: 2.2 to 21.1)]. The overall virological failure rate was low. The adverse event rate was similar between arms (except drug hypersensitivity, reported more in the abacavir/lamivudine arm). CONCLUSIONS: The study showed no difference in estimated glomerular filtration rate between the arms, however, increases in markers of tubular dysfunction were observed in the tenofovir/emtricitabine arm, the long-term consequence of which is unclear. A significant difference in efficacy favoring tenofovir/emtricitabine was observed.
- HPV type-specific distribution in a group of women attending at Hospital Fernando Fonseca, LisbonPublication . Santos, S; Pista, A; Pedro, A; Álvares, C; Ribeiro, C; Costa, C; Inácio, N; Pereira, S; Verdasca, NIntroduction: Genital HPV infection is very frequent. Nevertheless, type-specific distribution can vary greatly in different populations. Aim: To assess the HPV frequency and type-specific distribution in a highly ethnically diverse region and its association with gynecological cytology. Material and Methods: From March to July 2009, 419 LBC samples (ThinPrep) were collected from women 16-79 years old, attending Hospital Fernando Fonseca and associated Primary Health Care Centers. HPV genotyping was performed using CLINICAL ARRAY HPV 2. Statistical analysis was performed (Chi-Square test). Results: Out of 419 women (median age: 41 years), 74.0% were Caucasian and 21.0% African. Overall, 90.2% of the women had a normal cytology, 4.3% had ASCUS, 3.1% LSIL, 1.7% HSIL, and 0.7% had invasive carcinoma. HPV infection was detected in 25.8% of the cases, whereas in 75.0% of women between 20-45 years. HR-HPV genotypes were identified in 57.8% of the infected women. The most frequent HR-HPV types were HPV16 (11.4%), HPV52 (8.5%), HPV31 and 58 (7.2% each). Multiple infections (2-6 genotypes) were observed in 34.2%. HPV58, 16, 31, and 52 (9.5%, 7.4%, 7.4%, 7.4%, respectively) were the most frequent genotypes. HPV DNA was detected in 19.6% of the women with normal cytology, of which 31.0% had multiple infections. In ASCUS, LSIL, HSIL and invasive carcinoma, HPV was detected in 66.7%, 100%, 100%, and 66.7%, respectively. HPV16, 31, 52, 58 and 42 were most frequent among Caucasian and HPV16, 83, 52, 53 and 54 among African women. HPV16 and 18 were found in 4.5% and 1.0% of the women. Infection by multiple HPV was related to lesion grade (p=0.042). Conclusion: Our results are consistent with the data observed in the literature. Our findings can help achieve a better understanding of the wide spectrum of HPV infection and can contribute to a baseline for future assessment of screening and immunization strategies.
- Tipos de HPV num grupo de mulheres da área de influência do Hospital Fernando Fonseca, EPE, Amadora, PortugalPublication . Santos, S; Pista, A; Pedro, A; Álvares, C; Ribeiro, C; Costa, C; Inácio, N; Pereira, S; Verdasca, N
- Peginterferon alfa-2a (40KD) plus 800 or 1000/1200 mg/day ribavirin in genotype 1 HIV–HCV co-infected patients: early responses to treatment and predictability for SVR in the PARADIGM studyPublication . Rodriguez-Torres, M; Slim, J; Bhatti, L; Sterling, R; Hassanein, T; Clotet, B; Branco, T; Bertasso, A; Stancic, S; Sulkowski, M