Preventing tuberculosis-associated immune reconstitution inflammatory syndrome in high-risk patients : a randomised placebo-controlled trial of prednisone (PREDART)

Tuberculosis (TB) is the most common opportunistic infection amongst HIV-infected patients starting antiretroviral therapy (ART) in developing countries and thus the most frequent form of immune reconstitution inflammatory syndrome (IRIS). Paradoxical TB-IRIS occurs in 8-43% of patients starting ART while on TB treatment and results in morbidity, hospitalisation, consumes health care resources and neurological TB-IRIS is frequently fatal. We have previously demonstrated in a clinical trial that prednisone reduces morbidity when used for treatment of paradoxical TB-IRIS. Here we propose a placebo-controlled trial of prophylactic prednisone (40mg for 2 weeks followed by 20mg for 2 weeks, started on the same day as ART) in patients with TB who are identified as being at high risk for paradoxical TB-IRIS (starting ART within 30 days of TB diagnosis and CD4 ≤ 100/μL). The trial will enrol 240 participants, randomised 1:1. The primary endpoint is development of paradoxical TB-IRIS, defined using international consensus case definitions. Secondary endpoints include time to IRIS event, severity of IRIS, quality of life assessment, mortality and corticosteroids adverse events. The trial is powered to determine a reduction in TB-IRIS events. If results of this trial demonstrate benefit and safety, our intention is to take this intervention forward into a larger phase 3 clinical trial with mortality as primary endpoint.