Randomized placebo-controlled trial of prednisone for paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome.
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.
Meintjes
Graeme
G
Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South. graemein@mweb.co.za
Wilkinson
Robert J
RJ
Morroni
Chelsea
C
Pepper
Dominique J
DJ
Rebe
Kevin
K
Rangaka
Molebogeng X
MX
Oni
Tolu
T
Maartens
Gary
G
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
D005938:Glucocorticoids; D010919:Placebos; D011241:Prednisone
N Engl J Med. 2004 Oct 21;351(17):1741-51
15496623
Clin Infect Dis. 2009 Mar 1;48(5):677-9
19191656
Clin Infect Dis. 2009 Mar 1;48(5):667-76
19191655
J Infect Dis. 2009 Dec 1;200(11):1736-45
19874177
MMWR Recomm Rep. 2004 Dec 17;53(RR-15):1-112
15841069
J Infect Dis. 2004 Sep 1;190(5):869-78
15295690
Int J Tuberc Lung Dis. 2003 Mar;7(3):208-13
12661833
J Acquir Immune Defic Syndr. 2004 Dec 15;37(5):1574-6
15577411
Lancet Infect Dis. 2008 Aug;8(8):516-23
18652998
Int J Tuberc Lung Dis. 2007 Dec;11(12):1282-9
18229435
Lancet Infect Dis. 2005 Jun;5(6):361-73
15919622
Q J Med. 1992 Nov-Dec;85(307-308):855-60
1484947
Int J Tuberc Lung Dis. 2004 Sep;8(9):1114-9
15455597
Heart. 2000 Aug;84(2):183-8
10908256
Thorax. 2004 Aug;59(8):704-7
15282393
J Infect. 2006 Dec;53(6):357-63
16487593
AIDS. 2006 Jan 9;20(2):F1-7
16511406
AIDS. 2005 Mar 4;19(4):399-406
15750393
Qual Life Res. 1997 Aug;6(6):481-93
9330549
Lancet. 1988 Oct 1;2(8614):759-64
2901610
Am J Respir Crit Care Med. 2008 Nov 15;178(10):1083-9
18755923
J Infect Dis. 2007 Aug 15;196 Suppl 1:S63-75
17624828
AIDS. 2008 Mar 12;22(5):663-5
18317012
Clin Infect Dis. 2004 Dec 1;39(11):1709-12
15578375
AIDS. 2007 Jan 30;21(3):335-41
17255740
Am J Respir Crit Care Med. 1998 Jul;158(1):157-61
9655723
Br Med J (Clin Res Ed). 1983 Mar 19;286(6369):923-5
6403136
Antivir Ther. 2005;10(3):417-22
15918332
Am J Respir Crit Care Med. 2003 Feb 15;167(4):603-62
12588714