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INF - Artigos publicados em revistas indexadas

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Browsing INF - Artigos publicados em revistas indexadas by Subject "Antiretrovirais"

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  • Effect of efavirenz on high-density lipoprotein antioxidant properties in HIV-infected patients
    Publication . Pereira, S; Batuca, J; Caixas, U; Branco, T; Delgado-Alves, J; Germano, I; Lampreia, F; Monteiro, E
    WHAT 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.
    2009Journal article Open access Show more
  • Evidence for nevirapine bioactivation in man: Searching for the first step in the mechanism of nevirapine toxicity.
    Publication . Caixas, U; Antunes, A; Marinho, A; Godinho, A; Grilo, N; Marques, M; Oliveira, M; Branco, T; Monteiro, E; Pereira, S
    Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor used against human immunodeficiency virus type-1 (HIV-1), mostly to prevent mother-to-child HIV-1 transmission in developing countries. Despite its clinical efficacy, NVP administration is associated with a variety of toxic responses that include hepatotoxicity and skin rash. Although the reasons for the adverse effects of NVP administration are still unclear, increasing evidence supports the involvement of metabolic activation to reactive electrophiles. In particular, Phase II activation of the NVP metabolite 12-hydroxy-NVP is thought to mediate NVP binding to bionucleophiles, which may be at the onset of toxicity. In the present study, we investigated the nature and specific locations of the covalent adducts produced in human serum albumin and human hemoglobin by reaction in vitro with the synthetic model electrophile 12-mesyloxy-NVP, used as a surrogate for the Phase II metabolite 12-sulfoxy-NVP. Multiple sites of modification were identified by two different mass spectrometry-based methodologies, liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) and matrix-assisted laser desorption ionization tandem mass spectrometry (MALDI-TOF-TOF-MS). These two distinct methodologies, which in some instances afforded complementary information, allowed the identification of multiple adducts involving cysteine, lysine, tryptophan, histidine, serine, and the N-terminal valine of hemoglobin. Tryptophan, which is not a common site of covalent protein modification, was the NVP-modified amino acid residue detected in the two proteins and consistently identified by both LC-ESI-MS/MS and MALDI-TOF-TOF-MS. The propensity of tryptophan to react with the NVP-derived electrophile is further emphasized by the fact that human serum albumin possesses a single tryptophan residue, which suggests a remarkable selectivity that may be useful for biomonitoring purposes. Likewise, the NVP adduct with the terminal valine of hemoglobin, detected by LC-ESI-MS/MS after N-alkyl Edman degradation, appears as an easily assessed marker of NVP binding to proteins. Our results demonstrate the merits and complementarity of the two MS-based methodologies for the characterization of protein binding by NVP and suggest a series of plausible biomarkers of NVP toxicity that should be useful in the monitoring of toxicity effects in patients administered NVP.
    2012Journal article Restricted access Show more
  • Herpes hipertrófico perianal tratado eficazmente com imiquimod
    Publication . Lestre, S; João, A; Carvalho, C; Serrão, W
    A infecção pelo vírus herpes simples tipo 2 (HSV-2) é frequente em pacientes infetados pelo vírus de imunodeficiência adquirida (VIH). Nestes casos, o herpes genital pode ter uma apresentação clínica atípica. As variantes hipertróficas e vegetantes são pouco habituais. Os autores relatam um caso de herpes hipertrófico perianal em paciente infetada pelo VIH, com resposta insatisfatória ao aciclovir e valaciclovir, tratado eficazmente com imiquimod tópico. O herpes genital hipertrófico é, frequentemente, refratário aos tratamentos antivirais. Na nossa experiência, o imiquimod é um tratamento eficaz, seguro e bem tolerado que deverá ser considerado na abordagem terapêutica destes pacientes.
    2011Journal article Open access Show more
  • 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 study
    Publication . 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, M
    BACKGROUND: 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.
    2010Journal article Open access Show more
  • Recent advances in antiretroviral treatment and prevention in HIV-infected patients
    Publication . Maltez, F; Doroana, M; Branco, T; Valente, C
    PURPOSE OF REVIEW: To discuss new antiretroviral agents (ARVs) and alternative ARV treatment strategies that are currently being evaluated, and to provide an overview of the most recent advances in HIV vaccine development. RECENT FINDINGS: There is a continuous need for improvements in ARV therapy (ART) and several new ARVs are currently undergoing clinical investigation, including the non-nucleoside reverse transcriptase inhibitor rilpivirine, the integrase inhibitor elvitegravir, the chemokine receptor 5 co-receptor antagonist vicriviroc and the maturation inhibitor bevirimat. Strategies to optimize ART, such as treatment interruption, induction-maintenance and class-sparing regimens, are also being evaluated and have had varying success to date. However, vaccination still remains the optimal solution, and one second-generation preventative HIV vaccine has produced encouraging results in a recent phase III trial. SUMMARY: Global prevention and treatment with ARVs that are effective, well tolerated and have high barriers to the development of HIV resistance are the main strategies to fight HIV/AIDS while we await the development of an effective vaccine.
    2011Journal article Open access Show more
  • 2007Journal article Open access Show more