Tuberculosis risk factors and mortality for HIV-infected persons receiving antiretroviral therapy in South Africa

OBJECTIVE: To determine important risk factors for and impact of tuberculosis on survival in HIV-infected patients starting antiretroviral therapy (ART) in South Africa. DESIGN: Prospective trial of 1771 HIV-infected patients with either CD4 cell count less than 200 cells/microl or a prior AIDS-defining illness, enrolled in randomized trial of four antiretroviral regimens. METHODS: Data collected from patient records. RESULTS: A history of tuberculosis at study entry was reported by 27% of patients and correlated with poor baseline health status. A history of tuberculosis at baseline was associated with subsequent tuberculosis and death during ART, but was not itself an independent risk factor for poor outcome. Tuberculosis was diagnosed during ART in 14% of patients and was more frequent during the first 3 months. Tuberculosis during therapy was independently associated with increased hazard of other AIDS-defining events and death, regardless of when during ART tuberculosis occurred. ART that consistently suppressed circulating viremia reduced but did not eliminate tuberculosis risk. CONCLUSION: In HIV-infected patients who started ART at low CD4 cell counts, tuberculosis at baseline was a predictor of death, but was not independent of other factors indicating poor baseline health status. Tuberculosis during follow-up was, in contrast, an independent predictor of death even after adjustments for baseline risk factors, including CD4 cell count and viral load. Virologic failure during ART was associated with a 55% increase in risk of tuberculosis. Thus, tuberculosis is a major marker for poor outcome both at baseline and during ART and is not completely eliminated by fully suppressive ART.