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Prednisone for prevention of paradoxical tuberculosis-associated IRIS

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Title: Prednisone for prevention of paradoxical tuberculosis-associated IRIS
Authors: Meintjes, G
Stek, C
Bluementhal, L
Thienemann, F
Schutz, C
Buyze, J
Ravinetto, R
Van Loen, H
Nair, A
Jackson, A
Colebunders, R
Maartens, G
Wilkinson, RJ
Lynen, L
Item Type: Journal Article
Abstract: Background: Early initiation of antiretroviral therapy (ART) in patients with tuberculosis reduces mortality in those with low CD4 counts, but increases the risk of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS). We determined whether prophylactic prednisone safely reduces the incidence of paradoxical TB-IRIS in patients at high risk. Methods: Randomized, double-blind, placebo-controlled trial of prednisone (40 mg/day for 14 days, then 20 mg/day for 14 days) started with ART in ART-naïve adults at high risk of TB-IRIS (within 30 days of antituberculosis treatment initiation and CD4 count ≤100 cells/μl). Primary endpoint was development of TB-IRIS within 12 weeks, adjudicated by an independent committee. Results: Among 240 participants median age was 36 (IQR=30-42), 60% male, and median CD4 49 cells/μl (IQR=24-86). 18 participants were lost to follow-up or withdrew. TB-IRIS was diagnosed in 56 in the placebo arm (46.7%) and 39 in the prednisone arm (32.5%) (relative risk (RR)=0.70 (95%CI=0.51-0.96); p=0.03). Open-label corticosteroids to treat TB-IRIS were prescribed to 34 of the placebo arm (28.3%) and 16 (13.3%) of the prednisone arm (RR=0.47 (95%CI=0.27-0.81)). 4 deaths occurred in the placebo arm; 5 in the prednisone arm (p=1.0). Severe infections (AIDS-defining or invasive bacterial) occurred in 18 in the placebo arm; 11 in the prednisone arm (p=0.23). One Kaposi’s sarcoma case occurred (placebo arm). Conclusions: Prednisone during the first 4 weeks of initation of ART for HIV-1 infection reduced TB associated IRIS without evidence for increased risk of severe infections or malignancy.
Issue Date: 15-Nov-2018
Date of Acceptance: 23-Jun-2018
URI: http://hdl.handle.net/10044/1/64681
DOI: https://dx.doi.org/10.1056/NEJMoa1800762
ISSN: 0028-4793
Publisher: Massachusetts Medical Society
Start Page: 1915
End Page: 1925
Journal / Book Title: New England Journal of Medicine
Volume: 379
Copyright Statement: © 2018 Massachusetts Medical Society
Sponsor/Funder: Wellcome Trust
European and Developing Countries Clinical Trial P
European and Developing Countries Clinical Trials Partnership
Funder's Grant Number: 104803/Z/14/ZR
SRIA2015-1065
SRIA2015-1065
Keywords: PredART Trial Team
11 Medical And Health Sciences
General & Internal Medicine
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine



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