Reconstitution of Immune Responses to Tuberculosis in Patients With HIV Infection Who Receive Antiretroviral Therapy

• Published in: Chest Vol. 122; no. 2; pp. 597 - 602
• Main Authors: Schluger, Neil W., Perez, Daniel, Liu, Yuk Ming
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2002; American College of Chest Physicians
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; AIDS-Related Opportunistic Infections - complications; AIDS-Related Opportunistic Infections - immunology; Antiretroviral Therapy, Highly Active; Cell growth; Cohort Studies; Cytokines; Cytokines - metabolism; Drug resistance; Drug therapy; Female; HIV; HIV Infections - complications; HIV Infections - drug therapy; Human immunodeficiency virus; Humans; immunity; Infections; Interferon; Leukocytes, Mononuclear - immunology; Male; Middle Aged; Mycobacterium tuberculosis - immunology; Prospective Studies; T-Lymphocytes - immunology; treatment; Trends; Tuberculin Test; Tuberculosis; Tuberculosis - complications; Tuberculosis - immunology; IFN; treatment; ART; IL; PPD; tuberculosis; BCG; PHA; AIDS; immunity; PBMC
• ISSN: 0012-3692; 1931-3543
• DOI: 10.1378/chest.122.2.597

To assess the restoration of immune responses to tuberculosis, as manifested by secretion of T-helper type 1 cytokines (interferon [IFN]-γ, interleukin [IL]-12, and IL-2) and T-helper type 2 cytokines (IL-10), in HIV-positive patients who receive antiretroviral therapy (ART). Prospective cohort study. University hospital. Ten HIV-positive patients, all nai¨ve to ART and all about to start ART for clinical indications, and 11 healthy, HIV-negative control subjects. Assessment of T-cell proliferation and cytokine production after administration of ART to patients with HIV infection. All patients had a negative tuberculin skin test result at baseline and were anergic. Highly active ART reduced the viral load to very low levels in all patients within a short time after starting therapy. Blood samples were drawn every 2 months after starting therapy, and continued for 1 year while the patients continued to receive ART. There were trends toward increased proliferation of peripheral blood mononuclear cells (PBMCs) in response to Mycobacterium tuberculosis-specific stimuli, but these were delayed until several months of ART had elapsed. Similar trends were noted in relation to the secretion of IFN-γ. Neither PBMC proliferation nor IFN-γ secretion reached levels seen in healthy control subjects. No consistent trends in IL-2, IL-10, or IL-12 production were noted. ART restores immune responses to M tuberculosis, although this restoration is delayed and does not reach levels seen in healthy, HIV-negative control subjects. These results may explain in part the phenomenon of paradoxic reactions to antituberculosis therapy in patients with HIV infection. A larger study in which patients are followed up for a longer period of time will allow the magnitude and timing of this reconstitution to be more precisely defined.