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Journal of Virology, September 2001, p. 8690-8696, Vol. 75, No. 18
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.18.8690-8696.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Antiretroviral Agents Restore Mycobacterium-Specific T-Cell Immune Responses and Facilitate Controlling a Fatal Tuberculosis-Like Disease in Macaques Coinfected with Simian Immunodeficiency Virus and Mycobacterium bovis BCG

Yun Shen,1 Ling Shen,1 Prabhat Sehgal,2 Dejiang Zhou,1 Meredith Simon,2 Michael Miller,3 Emilio A. Enimi,4 Bill Henckler,4 Laura Chalifoux,2 Nitu Sehgal,1 Michael Gastron,2 Norman L. Letvin,1 and Zheng W. Chen1,*

Beth Israel Deaconess Center, Harvard Medical School, Boston, Massachusetts 022151; New England Regional Primate Research Center, Harvard Medical School, Southboro, Massachusetts 017722; Gilead Sciences, Foster City, California 944043; and Merck Inc., West Point, Pennsylvania4

Received 13 April 2001/Accepted 18 June 2001

The contribution of immune reconstitution following antiretroviral treatment to the prevention or treatment of human immunodeficiency virus-related primary or reactivation tuberculosis remains unknown. Macaque models of simian 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 macaques with active BCG reinfection and naive animals with simultaneous SIV/BCG coinfection were evaluated. The suppression of SIV replication by antiretroviral treatment resulted in control of the active BCG infection and blocked development of the fatal SIV-related tuberculosis-like disease. The resolution of this disease coincided with the restoration of BCG purified protein 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 died from tuberculosis-like disease. These results provide in vivo evidence that the restoration of anti-mycobacterial immunity by antiretroviral agents can improve the clinical outcome of an AIDS virus-related tuberculosis-like disease.

* Corresponding author. Mailing address: 330 Brookline Ave., RE113, Boston, MA 02215. Phone: (617) 667-2061. Fax: (617) 667-8210. E-mail: zchen{at}caregroup.harvard.edu.

Journal of Virology, September 2001, p. 8690-8696, Vol. 75, No. 18
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.18.8690-8696.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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Copyright © 2001 by the American Society for Microbiology. All rights reserved.