Randomized placebo-controlled trial of prednisone for paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome

AIDS. 2010 Sep 24;24(15):2381-90. doi: 10.1097/QAD.0b013e32833dfc68.


Objective: Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of antiretroviral therapy in resource-limited countries. We aimed to assess whether a 4-week course of prednisone would reduce morbidity in patients with paradoxical TB-IRIS without excess adverse events.

Design: A randomized, double-blind, placebo-controlled trial of prednisone (1.5 mg/kg per day for 2 weeks then 0.75 mg/kg per day for 2 weeks). Patients with immediately life-threatening TB-IRIS manifestations were excluded.

Methods: The primary combined endpoint was days of hospitalization and outpatient therapeutic procedures, which were counted as one hospital day.

Results: One hundred and ten participants were enrolled (55 to each arm). The primary combined endpoint was more frequent in the placebo than the prednisone arm {median hospital days 3 [interquartile range (IQR) 0-9] and 0 (IQR 0-3), respectively; P = 0.04}. There were significantly greater improvements in symptoms, Karnofsky score, and quality of life (MOS-HIV) in the prednisone vs. the placebo arm at 2 and 4 weeks, but not at later time points. Chest radiographs improved significantly more in the prednisone arm at weeks 2 (P = 0.002) and 4 (P = 0.02). Infections on study medication occurred in more participants in prednisone than in placebo arm (27 vs. 17, respectively; P = 0.05), but there was no difference in severe infections (2 vs. 4, respectively; P = 0.40). Isolates from 10 participants were found to be resistant to rifampicin after enrolment.

Conclusion: Prednisone reduced the need for hospitalization and therapeutic procedures and hastened improvements in symptoms, performance, and quality of life. It is important to investigate for drug-resistant tuberculosis and other causes for deterioration before administering glucocorticoids.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active / adverse effects*
  • CD4 Lymphocyte Count
  • Double-Blind Method
  • Glucocorticoids / therapeutic use*
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • Humans
  • Immune Reconstitution Inflammatory Syndrome / drug therapy*
  • Immune Reconstitution Inflammatory Syndrome / immunology
  • Male
  • Middle Aged
  • Placebos
  • Prednisone / therapeutic use*
  • Treatment Outcome
  • Tuberculosis / drug therapy*
  • Tuberculosis / immunology
  • Young Adult


  • Glucocorticoids
  • Placebos
  • Prednisone

Associated data

  • ISRCTN/ISRCTN21322548