RESUMO
HIV infection is a major risk factor predisposing for Mycobacterium tuberculosis infection and progression to active tuberculosis (TB). As host immune response defines the course of infection, we aimed to identify immuno-endocrine changes over six-months of anti-TB chemotherapy in HIV+ people. Plasma levels of cortisol, DHEA and DHEA-S, percentages of CD4+ regulatory T cell subsets and number of IFN-γ-secreting cells were determined. Several cytokines, chemokines and C-reactive protein levels were measured. Results were correlated with clinical parameters as predictors of infection resolution and compared to similar data from HIV+ individuals, HIV-infected persons with latent TB infection and healthy donors. Throughout the course of anti-TB/HIV treatment, DHEA and DHEA-S plasma levels raised while cortisol diminished, which correlated to predictive factors of infection resolution. Furthermore, the balance between cortisol and DHEA, together with clinical assessment, may be considered as an indicator of clinical outcome after anti-TB treatment in HIV+ individuals. Clinical improvement was associated with reduced frequency of unconventional Tregs, increment in IFN-γ-secreting cells, diminution of systemic inflammation and changes of circulating cytokines and chemokines. This study suggests that the combined anti-HIV/TB therapies result in partial restoration of both, immune function and adrenal hormone plasma levels.
Assuntos
Corticosteroides/sangue , Antituberculosos/uso terapêutico , Infecções por HIV/sangue , HIV-1/patogenicidade , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/tratamento farmacológico , Adulto , Biomarcadores/sangue , Coinfecção , Citocinas/sangue , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona/sangue , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/imunologia , Interações Hospedeiro-Patógeno , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/patogenicidade , Estudos Prospectivos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/microbiologia , Linfócitos T Reguladores/virologia , Fatores de Tempo , Resultado do Tratamento , Tuberculose/sangue , Tuberculose/imunologia , Tuberculose/microbiologiaRESUMO
Treatment of human immunodeficiency virus type 1 (HIV-1, causative agent of AIDS) infection represents a major challenge in antiviral therapeutics. Many difficulties are associated with the treatment, including toxicity, resistance and high costs. Taking this into account, research for novel compounds able to overcome these limitations is needed. Sulfated polysaccharides appear to be interesting, given their abundance as components of seaweeds. Herein, a series of fractions obtained from the brown seaweed Adenocystis utricularis was analysed for in vitro anti-HIV-1 activity. These fractions, which have anti-herpes simplex virus activity, were determined previously to belong to the family of fucoidans, sulfated polysaccharides obtained from the cell walls of brown seaweeds. Assays in human PBMC primary cell culture demonstrated that two of the five fractions analysed had potent anti-HIV-1 activity both against WT and drug-resistant HIV-1 strains. For active fractions, it was also shown that the inhibitory effect was not due to an inactivating effect on the viral particle (i.e. no virucidal activity was detected) but rather to a blockade of early events of viral replication. Given these encouraging results, these seaweed-derived fractions appear as good candidates for further studies on their potential for in vivo therapy and/or prophylaxis of HIV-1 infection.