Abstract
BackgroundHIV-infected individuals with latent TB infection are at increased risk of developing active TB. HAART greatly reduces the incidence rate of TB in HIV-infected patients and reconstitutes Mycobacterium tuberculosis (M. tuberculosis)-specific immune response in the first 12 months of therapy. The durability of the anti-mycobacterial immune restoration after a year of HAART however remains less investigated.MethodA cross-sectional study was conducted to evaluate M. tuberculosis-specific functional immune responses in HIV/latent TB co-infected patients who were on HAART for at least 1.5 up to 9 years as compared to HAART-naïve patients. Three-hundred sixteen HIV-infected patients without active TB were screened by tuberculin skin testing for M. tuberculosis infection and peripheral blood mononuclear cells (PBMCs) were isolated from 61 HIV/latent TB co-infected patients (30 HAART-naïve and 31 HAART-treated). IFN-γ and IL-2 ELISPOT as well as CFSE cell proliferation assays were performed after stimulation with M. tuberculosis antigens PPD and ESAT-6.ResultThe median frequency of PPD and ESAT-6 specific IFN-γ secreting cells was significantly higher in the HAART-treated patients as compared to HAART-naïve patients, p = 0.0021 and p = 0.0081 respectively. However, there was no significant difference in the median frequency of IL-2 secreting cells responding to PPD (p = 0.5981) and ESAT-6 (p = 0.3943) antigens between HAART-naïve and-treated groups. Both IFN-γ and IL-2 responses were independent of CD4+ T cell count regardless of the HAART status. Notably, the frequency of PPD and ESAT-6 specific IL-2 secreting cells was positively associated with CD4+ T cell proliferation while inversely correlated with duration of HAART, raising the possibility that M. tuberculosis-specific IL-2 response that promote the antigen-specific CD4+ T cell proliferation diminish with time on antiretroviral therapy in HIV/latent TB co-infected patients.ConclusionThis study shows an increased M. tuberculosis-specific IFN-γ, but not IL-2, response in HIV/latent TB co-infected patients with long-term HAART, consistent with only partial immune restoration. Future studies should, therefore, be done to prospectively define the rate and extent to which functional immune responses to M. tuberculosis are restored after long-term HAART.
Highlights
Human immunodeficiency virus (HIV)-infected individuals with latent TB infection are at increased risk of developing active TB
Be done to prospectively define the rate and extent to which functional immune responses to M. tuberculosis are restored after long-term Highly active anti-retroviral therapy (HAART)
Demographic and clinical information Sixty-one HIV-infected patients with latent TB infection were enrolled for the purpose this study and of these, were HAART-naïve and received HAART for more than a year
Summary
HIV-infected individuals with latent TB infection are at increased risk of developing active TB. Immunocompetent individuals control the infection by containing the mycobacteria in an inactive or latent state Both the innate and adaptive arms of the immune system are involved in a collaborative way to control infection with M. tuberculosis and subsequent disease. Following acquisition of HIV infection, the risk of reactivation of latent TB infection to active TB increases to 5–10% each year [3, 9]. This high rate of active TB development might be directly related to HIVderived weakened host cell-mediated immunity in general, and impaired M. tuberculosis-specific immune responses in particular. M. tuberculosis-specific production of interferon-(IFN)-γ, interleukin (IL)-2 and Tumor necrosis factor (TNF)-α by T cells contribute substantially to elicit effective immunity to prevent reactivation of latent TB infection [7, 10,11,12]
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