title: 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.
abstract: 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.
authors.affiliation: Beth Israel Deaconess Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.forename: L
authors.initials: L
authors.lastname: Shen
authors.forename: P
authors.initials: P
authors.lastname: Sehgal
authors.forename: D
authors.initials: D
authors.lastname: Zhou
authors.forename: M
authors.initials: M
authors.lastname: Simon
authors.forename: M
authors.initials: M
authors.lastname: Miller
authors.forename: E A
authors.initials: EA
authors.lastname: Enimi
authors.forename: B
authors.initials: B
authors.lastname: Henckler
authors.forename: L
authors.initials: L
authors.lastname: Chalifoux
authors.forename: N
authors.initials: N
authors.lastname: Sehgal
authors.forename: M
authors.initials: M
authors.lastname: Gastron
authors.forename: N L
authors.initials: NL
authors.lastname: Letvin
authors.forename: Z W
authors.initials: ZW
authors.lastname: Chen
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D019469:Indinavir / Q000627:therapeutic use*; D008253:Macaca mulatta; D008254:Macaca nemestrina; D009163:Mycobacterium bovis / Q000187:drug effects*; D019888:Nelfinavir / Q000627:therapeutic use*; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D000068698:Tenofovir; D014376:Tuberculosis / Q000276:immunology / Q000503:physiopathology*
chemical_list: D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D019469:Indinavir; D000068698:Tenofovir; D019888:Nelfinavir; D000225:Adenine