S-95. TB/HIV interaction and its impact on the immune system

Tuberculosis continues to be the most prevalent cause of death from an infectious agent globally, and its interaction with HIV is having devastating effects. HIV infection has emerged as by far the most important of all the predisposing factors for the development of TB (primary or re-activation), and TB is often the sentinel illness of HIV infection. TB causes worsening of HIV disease status, increases viral replication, decreases immunity, and hastens the onset of AIDS.

To test the hypothesis that HIV infection brings about an alteration in the immune response to tuberculosis (TB), mycobacterial antigen-induced production and plasma levels of the inflammatory cytokine interferon-g (IFN-g) and its regulatory cytokines interleukin-12 (IL-12), IL-18, and IL-10 were determined in patients infected dually with HIV and TB and compared with individuals with either disease and with healthy controls. Peripheral blood mononuclear cells (PBMCs) of TB patients with HIV infection produced lesser amounts of IFN-g and IL-12 compared with TB patients without HIV infection after in vitro stimulation with mycobacterial antigens. There was no difference in antigen-induced IL-18 production in TB patients with or without HIV infection. The in vivo cytokine pattern did not correlate with that seen in vitro. Higher levels of IFN-g, IL-12, and IL-18 were detected in the plasma of TB patients infected with HIV compared with TB patients without HIV infection. The presence of significantly higher plasma levels of proinflammatory cytokines suggests a greater degree of immune activation in individuals with HIV and TB, particularly those with low CD4 counts. In vitro IL-10 production by HIV-positive TB patients was similar to that of the HIV-negative TB group and higher than in HIV-positive individuals without TB, but the plasma levels were similar. HIV infection down-regulates the in vitro Th1 cytokine response to TB and simultaneously increases systemic levels of these cytokines. Immune activation markers e.g neopterin, microglobulin and sTNF-RI were compared at baseline and after 6 months of anti0TB treatrment in TB patients with and without HIV infection. Immune activation persisted well above normal limits in patients with HIV and TB, even after TB was successfully cured. Further, we have examined apoptosis of PBMC in individuals with HIV alone, TB alone and both infections. The increased spontaneous apoptosis seen in patients with HIV and TB could explain partly the increased immunosuppression seen in this group. Patients with HIV/AIDS have both immunosuppression and immune activation simultaneously which have detrimental effects on the progression and outcome of the two infections.