Antiretroviral agents restore mycobacterium-specific T-cell immune responses and facilitate controlling a fatal tuberculosis-like disease in macaquescoinfected with simian immunodeficiency virus and Mycobacterium bovis BCG

The contribution of immune reconstitution following antiretroviral treatmen t to the prevention or treatment of human immunodeficiency virus-related pr imary or reactivation tuberculosis remains unknown. Macaque models of simia n immunodeficiency virus-Mycobacterium bovis BCG (SIV/BCG) coinfection were employed to determine the extent to which anti-Mycobacterium tuberculosis immunity can be restored by antiretroviral therapy. Both SIV-infected macaq ues with active BCG reinfection and naive animals with simultaneous SIV/BCG coinfection were evaluated. The suppression of SIV replication by antiretr oviral treatment resulted in control of the active BCG infection and blocke d development of the fatal SIV-related tuberculosis-like disease. The resol ution of this disease coincided with the restoration of BCG purified protei n derivative (PPD)-specific T-cell immune responses. In contrast, macaques similarly coinfected with SIV/BCG but not receiving antiretroviral therapy had depressed PPD-specific primary and memory T-cell immune responses and d ied from tuberculosis-like disease. These results provide in vivo evidence that the restoration of antimycobacterial immunity by antiretroviral agents can improve the clinical outcome of an AIDS virus-related tuberculosis-lik e disease.