Preventing Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in High-Risk Patients: Protocol of a Randomized Placebo-Controlled Trial of Prednisone (PredART Trial).

backgroundEarly antiretroviral therapy (ART) initiation in patients diagnosed with HIV-associated tuberculosis (TB) reduces mortality among those with the lowest CD4 counts. At the same time, both early ART and a low CD4 count heighten the risk of paradoxical TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). TB is common in patients starting ART in sub-Saharan Africa. Safe interventions that reduce the incidence or severity of TB-IRIS are needed. Prednisone has been shown to reduce symptoms and markers of inflammation when used to treat TB-IRIS.

objectiveTo determine whether prophylactic prednisone in patients at high risk for paradoxical TB-IRIS initiating ART reduces the incidence of TB-IRIS.

methodsWe are conducting a randomized, double-blind, placebo-controlled trial of prophylactic prednisone (40 mg/day for 2 weeks, followed by 20 mg/day for 2 weeks) initiated at the same time as ART in patients at high risk for TB-IRIS (starting ART within 30 days of TB treatment and CD4 count ≤100/μL). The primary endpoint is development of TB-IRIS, defined using an international consensus case definition. Secondary endpoints include time to TB-IRIS event, severity of TB-IRIS, quality of life, mortality, hospitalization, other infections and malignancies, and adverse events including corticosteroid adverse effects.

resultsEnrollment for the trial began in August 2013. All 240 participants have been enrolled, and safety follow-up will be completed in March 2017.

conclusionNo preventive strategies for TB-IRIS currently exist. If results of this trial demonstrate the efficacy and safety of prednisone, this will provide clinicians with an evidence-based preventive strategy in patients at high risk for paradoxical TB-IRIS when initiating ART.