Meintjes G, et al. - Experts evaluated whether or not the incidence of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS) in patients at high risk for the syndrome can be safely reduced by prophylactic prednisone. A lower incidence of tuberculosis-associated IRIS was resulted by the prednisone treatment during the first 4 weeks after the initiation of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection vs placebo, without evidence of an increased risk of severe infections or cancers.

Methods

• In this randomized, double-blind, placebo-controlled trial, authors enrolled HIV-infected patients who were initiating ART (and had not previously received ART), had started tuberculosis treatment within 30 days before initiating ART, and had a CD4 count of 100 cells or fewer per microliter.
• The patients were administered either prednisone (at a dose of 40 mg per day for 14 days, then 20 mg per day for 14 days) or placebo.
• The development of tuberculosis-associated IRIS within 12 weeks after initiating ART, as adjudicated by an independent committee was the primary end point.

Results

• As per data, among the 240 enrolled patients, the median age was 36 (interquartile range, 30 to 42), 60% were men, and 73% had microbiologically confirmed tuberculosis; the median CD4 count was 49 cells per microliter (interquartile range, 24 to 86), and the median HIV type 1 RNA viral load was 5.5 log10 copies per milliliter (interquartile range, 5.2 to 5.9).
• They assigned a total of 120 patients to each group, and 18 patients were lost to follow-up or withdrew.
• Results demonstrated that 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).
• In 16 patients (13.3%) in the prednisone group and in 34 (28.3%) in the placebo group, open-label glucocorticoids were prescribed to treat tuberculosis-associated IRIS (relative risk, 0.47; 95% CI, 0.27 to 0.81).
• In the prednisone group, there were five deaths and there were four in the placebo group (P=1.00).
• In 11 patients, severe infections (acquired immunodeficiency syndrome–defining illnesses or invasive bacterial infections) occurred in the prednisone group and in 18 patients in the placebo group (P=0.23).
• Findings suggested that 1 case of Kaposi’s sarcoma occurred in the placebo group.