A randomized trial of punctuated antiretroviral therapy in Ugandan HIV-seropositive adults with pulmonary tuberculosis and CD4 T-cell counts of >/= 350 cells/muL.

Author(s): Nanteza MW, Mayanja-Kizza H, Charlebois E, Srikantiah P, Lin R, Mupere E, Mugyenyi P, Boom WH, Mugerwa RD, Havlir DV, Whalen CC

Affiliation(s): Uganda-Case Western Reserve University Research Collaboration, Makerere University, Kampala, Uganda.

Publication date & source: 2011-09-15, J Infect Dis., 204(6):884-92.

Publication type: Randomized Controlled Trial

BACKGROUND: Optimal treatment of human immunodeficiency virus (HIV)-associated tuberculosis in patients with high CD4 T-cell counts is unknown. Suppression of viral replication during therapy for tuberculosis may block effects of immune activation on T cells and slow HIV disease progression. METHODS: We conducted a randomized trial in 214 HIV-infected patients with active tuberculosis and CD4 T-cell counts of >/= 350 cells/muL to determine whether 6 months of antiretroviral therapy given during tuberculosis treatment would improve clinical outcomes. Subjects were randomized to receive 6 months of abacavir-lamivudine-zidovudine concurrent with tuberculosis therapy or delayed antiretroviral therapy. Endpoints were CD4 T-cell counts of < 250 cells/muL, AIDS, or death. RESULTS: Intervention and comparison arms had similar median CD4 counts (517 and 534 cells/muL, respectively) and HIV RNA levels (4.6 and 4.7 log copies/muL, respectively). Viral suppression was achieved in 86% of patients allocated to intervention. Seventeen subjects (15.6%) in the intervention arm developed study outcome compared to 25 subjects (22.8%) in the comparison arm (P = .17). Grade 3 or 4 adverse events were less frequent in the intervention arm. By 2 months, 90% of subjects in both arms were culture-negative for tuberculosis. CONCLUSIONS: Short-term antiretroviral therapy during tuberculosis treatment in patients with CD4T-cell counts of >350 cells/muL was safe and associated with clinical benefits.