Reconstitution of immune responses to tuberculosis in patients with HIV infection who receive antiretroviral therapy

STUDY OBJECTIVE:s: To assess the restoration of immune responses to tuberculosis, as manifested by secretion of T-helper type 1 cytokines (interferon [IFN]-gamma, interleukin [IL]-12, and IL-2) and T-helper type 2 cytokines (IL-10), in HIV-positive patients who receive antiretroviral therapy (ART). DESIGN: Prospective cohort study. SETTING: University hospital. PATIENTS: Ten HIV-positive patients, all na?ve to ART and all about to start ART for clinical indications, and 11 healthy, HIV-negative control subjects. INTERVENTIONS: Assessment of T-cell proliferation and cytokine production after administration of ART to patients with HIV infection. MEASUREMENTS AND RESULTS: 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-gamma. Neither PBMC proliferation nor IFN-gamma secretion reached levels seen in healthy control subjects. No consistent trends in IL-2, IL-10, or IL-12 production were noted. CONCLUSION: 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.