Background: Early initiation of antiretroviral therapy (ART) in patients with tuberculosis reduces mortality in those with low CD4 counts, but increases the risk of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS). We determined whether prophylactic prednisone safely reduces the incidence of paradoxical TB-IRIS in patients at high risk.

Methods: Randomized, double-blind, placebo-controlled trial of prednisone (40 mg/day for 14 days, then 20 mg/day for 14 days) started with ART in ART-naïve adults at high risk of TB-IRIS (within 30 days of antituberculosis treatment initiation and CD4 count ≤100 cells/μl). Primary endpoint was development of TB-IRIS within 12 weeks, adjudicated by an independent committee.

Results: Among 240 participants median age was 36 (IQR=30-42), 60% male, and median CD4 49 cells/μl (IQR=24-86). 18 participants were lost to follow-up or withdrew. TB-IRIS was diagnosed in 56 in the placebo arm (46.7%) and 39 in the prednisone arm (32.5%) (relative risk (RR)=0.70 (95%CI=0.51-0.96); p=0.03). Open-label corticosteroids to treat TB-IRIS were prescribed to 34 of the placebo arm (28.3%) and 16 (13.3%) of the prednisone arm (RR=0.47 (95%CI=0.27-0.81)). 4 deaths occurred in the placebo arm; 5 in the prednisone arm (p=1.0). Severe infections (AIDS-defining or invasive bacterial) occurred in 18 in the placebo arm; 11 in the prednisone arm (p=0.23). One Kaposi’s sarcoma case occurred (placebo arm).

Conclusions: Prednisone during the first 4 weeks of initation of ART for HIV-1 infection reduced TB associated IRIS without evidence for increased risk of severe infections or malignancy.