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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. Chen^1,*

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.

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^* 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.

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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.

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