Early initiation of antiretroviral therapy (ART) in human immunodeficiency virus infected patients who have tuberculosis reduces mortality among patients with low CD4 counts, but it increases the risk of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS). This study evaluated whether prophylactic steroids in this group would reduce the incidence of IRIS in this high risk population. HIV infected adult patients who had not previously received ART and now initiating ART with a CD4 count of 100 cells or less and microbiologically confirmed or clinically diagnosed TB with symptomatic response to ATT, and on ATT for less than 30 days before initiating ART were included in the trial. Patients in the prednisone group received 40 mg of prednisone per day for 14 days, followed by 20 mg per day for 14 days, and those in the placebo group received the equivalent number of placebo tablets. The prednisone or placebo was started within 48 hours after the initiation of ART.
This trial was done in Cape Town, South Africa. Of the 240 patients included in the trial, tuberculosis-associated IRIS was diagnosed in 39 patients (32.5%) in the prednisone group and in 56 (46.7%) in the placebo group (relative risk, 0.70; 95% confidence interval [CI], 0.51 to 0.96; P=0.03). Severe infections were not different between the two groups (P=0.23). There has been some concern of malignancies when HIV infected patients are treated with steroids. The authors did not find any.
Hence, this practice changing trial shows that prophylactic steroids can reduce the risk of TB IRIS in this select group of high risk patients.