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

(See the editorial commentary by Von Reyn, on pages 817–9.) The epidemics of tuberculosis and human immunodeficiency virus type 1 (HIV) infection converged with the greatest intensity in sub-Saharan Africa. Both the incidence and the prevalence of tuberculosis increased as the HIV infection epidemic swept through the continent. In Africa today, tuberculosis may affect up to 30% of coinfected persons [1] and is the leading cause of death. Even with effective antituberculosis treatment, case fatality rates for tuberculosis may be as high as 20%, especially in the face of severe immunosuppression [2, 3]. Moreover, tuberculosis may accelerate the clinical course of HIV infection and lead to poor outcomes [4–7]. Newly revised guidelines from the World Health Organization (WHO) recommend the use of antiretroviral therapy for all HIV-seropositive persons with tuberculosis disease, regardless of their CD4+ T-cell count [8]. Recent evidence indicates that antiretroviral therapy should be started early in the course of tuberculosis treatment because it improves survival [9, 10]. Although there is abundant information on the benefit of antiretroviral therapy in HIV-infected tuberculosis patients with advanced immunosuppression [11–13], there are fewer data on the optimal management of tuberculosis among patients with CD4+ T-cell counts of >350 cells/μL. The present study was designed in the early years of the antiretroviral therapy rollout in Africa to determine whether a 6-month course of antiretroviral therapy given concurrently with tuberculosis treatment would improve the clinical, immunologic, and virologic outcomes among patients with CD4+ T-cell counts of >350 cells/μL. The rationale of the study was that a punctuated course of antiretroviral therapy in patients with high CD4+ T-cell counts would suppress viral replication during therapy for tuberculosis, block the effects of immune activation on T cells harboring HIV, slow the pace of HIV disease progression, and improve clinical outcomes. Although treatment interruption is no longer a viable option given recent advances in the field of HIV infection management [14], the present study provides evidence of clinical benefit when starting antiretroviral therapy in tuberculosis patients with preserved immunity.