Background:  The paradoxical form of TB immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication in patients starting ART while on TB treatment in resource-limited countries. Anecdotal reports suggest that patients respond symptomatically to adjunctive corticosteroid therapy, but there are potential risks associated with this especially in advanced HIV infection.

Methods:  A double-blind placebo-controlled randomized clinical trial (RCT) of prednisone for TB-IRIS was conducted. Consecutive patients with suspected TB-IRIS were assessed using a clinical case definition. Patients with life-threatening TB-IRIS (neurological involvement, airway compression, and respiratory failure) were excluded. Study drug was prescribed at 1.5 mg/kg/day (2 weeks) then 0.75 mg/kg/day (2 weeks). Follow-up was 12 weeks. Patients deteriorating on or after study drug could be switched to open-label prednisone at the physician’s discretion. The primary endpoint was days of hospitalization (therapeutic procedures, e.g., drainage of effusion, were counted as a hospital day).

Results:  We enrolled 109 patients (55 to prednisone; 54 to placebo) of whom 70 (64%) were female and median age was 32. Median CD4 count prior to ART was 53 cells/µL, and at enrolment 116 cells/µL; 6 patients defaulted for more than 7 days or were lost to follow-up (all in the placebo arm, p = 0.01). Median number of hospital days was 1 (IQR 0 to 3) in prednisone arm vs 3 (IQR 0 to 11) in placebo arm (p = 0.05). Cumulatively there were 282 vs 463 days of hospitalization and 29 vs 38 procedures in the prednisone and placebo arms, respectively. There were 3 deaths in the prednisone arm and 2 in placebo arm (p = 0.7). During the 4 weeks of study drug, 5 patients switched to open-label prednisone in prednisone arm vs 19 in the placebo arm (p = 0.001). While on study drug, 9 patients had corticosteroid side effects in the prednisone arm vs 3 in the placebo (p = 0.07). Severe infections occurred in 2 in the prednisone arm vs 4 in the placebo arm (p = 0.4). A 5-point score demonstrated significant symptom improvement in prednisone vs placebo arm at 2 weeks (p = 0.003). After enrollment, 12 patients were diagnosed with rifampicin resistance (5 vs 7 in prednisone and placebo arms, p = 0.5).

Conclusions:  Prednisone reduced the need for hospitalization and procedures, and resulted in symptom improvement without an excess of corticosteroid side effects or severe infections. It is important to exclude drug-resistant TB and other causes for deterioration before using corticosteroids.