A Randomized Trial of Punctuated Antiretroviral Therapy in Ugandan HIV-Seropositive Adults With Pulmonary Tuberculosis and CD4+ T-Cell Counts of ≥350 cells/μL

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/mu L 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/mu L, AIDS, or death. Results. Intervention and comparison arms had similar median CD4(+) counts (517 and 534 cells/mu L, respectively) and HIV RNA levels (4.6 and 4.7 log(10) copies/mu L, 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 CD4(+) T-cell counts of >350 cells/mu L was safe and associated with clinical benefits.