title: Randomized placebo-controlled trial of prednisone for paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South. graemein@mweb.co.za
authors.forename: Graeme
authors.initials: G
authors.lastname: Meintjes
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
authors.forename: Chelsea
authors.initials: C
authors.lastname: Morroni
authors.forename: Dominique J
authors.initials: DJ
authors.lastname: Pepper
authors.forename: Kevin
authors.initials: K
authors.lastname: Rebe
authors.forename: Molebogeng X
authors.initials: MX
authors.lastname: Rangaka
authors.forename: Tolu
authors.initials: T
authors.lastname: Oni
authors.forename: Gary
authors.initials: G
authors.lastname: Maartens
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D005938:Glucocorticoids / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011241:Prednisone / Q000627:therapeutic use*; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy* / Q000276:immunology; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D010919:Placebos; D011241:Prednisone
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