ABSTRACT
BACKGROUND: Human immunodeficiency virus (HIV)-tuberculosis coinfection is associated with heightened immune activation, viral replication, and T cell dysfunction. We compared changes in T cell activation and function between patients receiving concurrent treatment for HIV-tuberculosis coinfection and those receiving treatment for tuberculosis alone. METHODS: HIV-infected adults with tuberculosis and CD4(+) T cell counts >350 cells/mm(3) were randomized to receive tuberculosis treatment alone (control arm; n = 36) or 6 months of antiretroviral therapy (ART) concurrent with tuberculosis treatment (intervention arm; n = 38). HIV viral load, T cell subsets, T cell activation, and cytokine production were measured at enrollment and every 3 months for 12 months. RESULTS: Differences in absolute CD4(+) and CD8(+) T cell counts were not observed between arms. Viral load was reduced while participants received ART; control patients maintained viral load at baseline levels. Both arms had significant reductions in T cell expression of CD38 and HLA-DR. Interferon-γ production in response to mitogen increased significantly in the intervention arm. CONCLUSIONS: In HIV-infected adults with tuberculosis and CD4(+) T cell counts >350 cells/mm(3), both tuberculosis treatment and concurrent HIV-tuberculosis treatment reduce T cell activation and stabilize T cell counts. Concurrent ART with tuberculosis treatment does not provide additional, sustained reductions in T cell activation among individuals with preserved immunologic function.
Subject(s)
Anti-HIV Agents/administration & dosage , Antiretroviral Therapy, Highly Active , Antitubercular Agents/administration & dosage , HIV Infections/drug therapy , HIV Infections/immunology , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/immunology , Adult , CD4 Lymphocyte Count , Cytokines/metabolism , Female , HIV Infections/complications , Humans , Male , Middle Aged , T-Lymphocyte Subsets/immunology , Treatment Outcome , Tuberculosis, Pulmonary/complicationsABSTRACT
BACKGROUND: Both HIV and TB cause a state of heightened immune activation. Immune activation in HIV is associated with progression to AIDS. Prior studies, focusing on persons with advanced HIV, have shown no decline in markers of cellular activation in response to TB therapy alone. METHODOLOGY: This prospective cohort study, composed of participants within a larger phase 3 open-label randomized controlled clinical trial, measured the impact of TB treatment on immune activation in persons with non-advanced HIV infection (CD4>350 cells/mm3) and pulmonary TB. HIV load, CD4 count, and markers of immune activation (CD38 and HLA-DR on CD4 and CD8 T cells) were measured prior to starting, during, and for 6 months after completion of standard 6 month anti-tuberculosis (TB) therapy in 38 HIV infected Ugandans with smear and culture confirmed pulmonary TB. RESULTS: Expression of CD38, and co-expression of CD38 and HLA-DR, on CD8 cells declined significantly within 3 months of starting standard TB therapy in the absence of anti-retroviral therapy, and remained suppressed for 6 months after completion of therapy. In contrast, HIV load and CD4 count remained unchanged throughout the study period. CONCLUSION: TB therapy leads to measurable decreases in immune activation in persons with HIV/TB co-infection and CD4 counts>350 cells/mm3.
Subject(s)
Antitubercular Agents/therapeutic use , HIV Infections/immunology , Tuberculosis/drug therapy , Viral Load/immunology , Adult , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cohort Studies , Ethambutol/therapeutic use , Female , Flow Cytometry , HIV Infections/complications , HIV-1/immunology , Humans , Isoniazid/therapeutic use , Male , Middle Aged , Prospective Studies , Pyrazinamide/therapeutic use , Rifampin/therapeutic use , Tuberculosis/complications , Uganda , Young AdultSubject(s)
HIV Infections/complications , Tuberculosis, Pulmonary/complications , Viremia/complications , Adolescent , Adult , Antitubercular Agents/therapeutic use , CD4 Lymphocyte Count , Female , HIV Infections/drug therapy , Humans , Male , RNA, Viral/blood , Tuberculosis, Pulmonary/drug therapy , Uganda , Viral LoadABSTRACT
Triple nucleoside reverse transcriptase inhibitors are recommended as an alternative regimen for HIV-infected patients undergoing tuberculosis treatment in resource-limited settings. Few data exist on the efficacy of such regimens in tuberculosis patients. In 34 tuberculosis/HIV-co-infected patients treated with zidovudine/lamivudine/abacavir, 76% achieved HIV RNA less than 50 copies/ml at 24 weeks. No cases of hypersensitivity or immune reconstitution syndrome were observed. These data support the continuing evaluation of nucleoside-based antiretroviral regimens as an alternative treatment for this population.