Immune variations throughout the course of tuberculosis treatment and its relationship with adrenal hormone changes in HIV-1 patients co-infected with Mycobacterium tuberculosis
Maria Belen Vecchione 1, Denise Anabella Giannone 1, Matías Tomás Angerami 1, Natalia Laufer 1;2, Omar Sued 3 and Maria Florencia Quiroga 1.
1 Universidad de Buenos Aires. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS). Facultad de Medicina. Buenos Aires, Argentina.
2 Hospital Juan A. Fernández. Buenos Aires, Argentina.
3 Área de Investigaciones Médicas. Fundación Huésped. Buenos Aires, Argentina.
Purpose: Risk of developing active TB among HIV-coinfected (HIV-TB) patients is 19 times higher than in HIV-negative individuals. Host's immune response determines resolution or dissemination of TB infection. We aimed to identify immuno-endocrine responses over a six-month follow-up of anti-tuberculous (anti-TB) treatment in HIV+ individuals that were associated with control of TB.
Methods: Plasma levels of cortisol, DHEA and DHEA-S (DHEA sulfate), percentages of CD4+ regulatory T cell subsets and number of IFN-γ-secreting cells were determined. Several cytokines, chemokines and C-reactive protein (CRP) levels were measured. Results were analyzed, correlated with clinical data and compared to similar data from HIV-1-monoinfected individuals, HIV infected individuals with latent TB infection and healthy donors.
Results: Throughout the course of anti-TB/HIV treatment, reduction of viral load (p<0.001) and increase of absolute CD4+ count (p<0.05) and CD4/CD8 ratio (p<0.05) were observed. DHEA (p<0.05) and DHEA-S (p<0.01) plasma levels raised while cortisol (p<0.05) diminished, which correlated to parameters underlying control of infections (CD4+ counts, CD4/CD8 ratio and lung-restricted TB infection). Furthermore, the balance between cortisol and DHEA may be used as predictor of anti-TB treatment efficacy in HIV+ individuals (p<0.005). Clinical improvement was associated with reduced frequency of unconventional Tregs (p<0.05), increment in Mycobacterium tuberculosis-specific IFN-γ-secreting cells (p<0.05) and diminution of systemic inflammation (CRP and IL-6, p<0.05). Finally, we found significant changes of circulating cytokines and chemokines.
Conclusion: This study suggests that the combined anti-HIV/TB therapies results in a recovery of the adrenal axis and immune responses toward similar values to HIV-chronically infected individuals and may expand the knowledge about specific treatment response in HIV-TB patients.