PMID- 30428290
OWN - NLM
STAT- MEDLINE
DCOM- 20181126
LR  - 20220129
IS  - 1533-4406 (Electronic)
IS  - 0028-4793 (Linking)
VI  - 379
IP  - 20
DP  - 2018 Nov 15
TI  - Prednisone for the Prevention of Paradoxical Tuberculosis-Associated IRIS.
PG  - 1915-1925
LID - 10.1056/NEJMoa1800762 [doi]
AB  - BACKGROUND: Early initiation of antiretroviral therapy (ART) in human 
      immunodeficiency virus (HIV)-infected patients who have tuberculosis reduces 
      mortality among patients with low CD4 counts, but it increases the risk of 
      paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome 
      (IRIS). METHODS: We conducted this randomized, double-blind, placebo-controlled 
      trial to assess whether prophylactic prednisone can safely reduce the incidence 
      of paradoxical tuberculosis-associated IRIS in patients at high risk for the 
      syndrome. We enrolled HIV-infected patients who were initiating ART (and had not 
      previously received ART), had started tuberculosis treatment within 30 days 
      before initiating ART, and had a CD4 count of 100 cells or fewer per microliter. 
      Patients received either prednisone (at a dose of 40 mg per day for 14 days, then 
      20 mg per day for 14 days) or placebo. The primary end point was the development 
      of tuberculosis-associated IRIS within 12 weeks after initiating ART, as 
      adjudicated by an independent committee. RESULTS: Among the 240 patients who were 
      enrolled, the median age was 36 (interquartile range, 30 to 42), 60% were men, 
      and 73% had microbiologically confirmed tuberculosis; the median CD4 count was 49 
      cells per microliter (interquartile range, 24 to 86), and the median HIV type 1 
      RNA viral load was 5.5 log(10) copies per milliliter (interquartile range, 5.2 to 
      5.9). A total of 120 patients were assigned to each group, and 18 patients were 
      lost to follow-up or withdrew. Tuberculosis-associated IRIS was diagnosed in 39 
      patients (32.5%) in the prednisone group and in 56 (46.7%) in the placebo group 
      (relative risk, 0.70; 95% confidence interval [CI], 0.51 to 0.96; P=0.03). 
      Open-label glucocorticoids were prescribed to treat tuberculosis-associated IRIS 
      in 16 patients (13.3%) in the prednisone group and in 34 (28.3%) in the placebo 
      group (relative risk, 0.47; 95% CI, 0.27 to 0.81). There were five deaths in the 
      prednisone group and four in the placebo group (P=1.00). Severe infections 
      (acquired immunodeficiency syndrome-defining illnesses or invasive bacterial 
      infections) occurred in 11 patients in the prednisone group and in 18 patients in 
      the placebo group (P=0.23). One case of Kaposi's sarcoma occurred in the placebo 
      group. CONCLUSIONS: Prednisone treatment during the first 4 weeks after the 
      initiation of ART for HIV infection resulted in a lower incidence of 
      tuberculosis-associated IRIS than placebo, without evidence of an increased risk 
      of severe infections or cancers. (Funded by the European and Developing Countries 
      Clinical Trials Partnership and others; PredART ClinicalTrials.gov number, 
      NCT01924286 .).
FAU - Meintjes, Graeme
AU  - Meintjes G
AD  - From the Wellcome Centre for Infectious Diseases Research in Africa, Institute of 
      Infectious Disease and Molecular Medicine (G. Meintjes, C. Stek, L.B., F.T., C. 
      Schutz, A.N., A.J., R.J.W.), the Department of Medicine (G. Meintjes, C. Stek, 
      F.T., C. Schutz, R.J.W.), and the Division of Clinical Pharmacology, Department 
      of Medicine (G. Maartens), University of Cape Town, Cape Town, South Africa; the 
      Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium 
      (C. Stek, J.B., R.R., H.L., R.C., L.L.); the Department of Internal Medicine, 
      University Hospital of Zurich, Zurich, Switzerland (F.T.); and the Department of 
      Medicine, Imperial College London and the Francis Crick Institute, London 
      (R.J.W.).
FAU - Stek, Cari
AU  - Stek C
AD  - From the Wellcome Centre for Infectious Diseases Research in Africa, Institute of 
      Infectious Disease and Molecular Medicine (G. Meintjes, C. Stek, L.B., F.T., C. 
      Schutz, A.N., A.J., R.J.W.), the Department of Medicine (G. Meintjes, C. Stek, 
      F.T., C. Schutz, R.J.W.), and the Division of Clinical Pharmacology, Department 
      of Medicine (G. Maartens), University of Cape Town, Cape Town, South Africa; the 
      Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium 
      (C. Stek, J.B., R.R., H.L., R.C., L.L.); the Department of Internal Medicine, 
      University Hospital of Zurich, Zurich, Switzerland (F.T.); and the Department of 
      Medicine, Imperial College London and the Francis Crick Institute, London 
      (R.J.W.).
FAU - Blumenthal, Lisette
AU  - Blumenthal L
AD  - From the Wellcome Centre for Infectious Diseases Research in Africa, Institute of 
      Infectious Disease and Molecular Medicine (G. Meintjes, C. Stek, L.B., F.T., C. 
      Schutz, A.N., A.J., R.J.W.), the Department of Medicine (G. Meintjes, C. Stek, 
      F.T., C. Schutz, R.J.W.), and the Division of Clinical Pharmacology, Department 
      of Medicine (G. Maartens), University of Cape Town, Cape Town, South Africa; the 
      Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium 
      (C. Stek, J.B., R.R., H.L., R.C., L.L.); the Department of Internal Medicine, 
      University Hospital of Zurich, Zurich, Switzerland (F.T.); and the Department of 
      Medicine, Imperial College London and the Francis Crick Institute, London 
      (R.J.W.).
FAU - Thienemann, Friedrich
AU  - Thienemann F
AD  - From the Wellcome Centre for Infectious Diseases Research in Africa, Institute of 
      Infectious Disease and Molecular Medicine (G. Meintjes, C. Stek, L.B., F.T., C. 
      Schutz, A.N., A.J., R.J.W.), the Department of Medicine (G. Meintjes, C. Stek, 
      F.T., C. Schutz, R.J.W.), and the Division of Clinical Pharmacology, Department 
      of Medicine (G. Maartens), University of Cape Town, Cape Town, South Africa; the 
      Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium 
      (C. Stek, J.B., R.R., H.L., R.C., L.L.); the Department of Internal Medicine, 
      University Hospital of Zurich, Zurich, Switzerland (F.T.); and the Department of 
      Medicine, Imperial College London and the Francis Crick Institute, London 
      (R.J.W.).
FAU - Schutz, Charlotte
AU  - Schutz C
AD  - From the Wellcome Centre for Infectious Diseases Research in Africa, Institute of 
      Infectious Disease and Molecular Medicine (G. Meintjes, C. Stek, L.B., F.T., C. 
      Schutz, A.N., A.J., R.J.W.), the Department of Medicine (G. Meintjes, C. Stek, 
      F.T., C. Schutz, R.J.W.), and the Division of Clinical Pharmacology, Department 
      of Medicine (G. Maartens), University of Cape Town, Cape Town, South Africa; the 
      Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium 
      (C. Stek, J.B., R.R., H.L., R.C., L.L.); the Department of Internal Medicine, 
      University Hospital of Zurich, Zurich, Switzerland (F.T.); and the Department of 
      Medicine, Imperial College London and the Francis Crick Institute, London 
      (R.J.W.).
FAU - Buyze, Jozefien
AU  - Buyze J
AD  - From the Wellcome Centre for Infectious Diseases Research in Africa, Institute of 
      Infectious Disease and Molecular Medicine (G. Meintjes, C. Stek, L.B., F.T., C. 
      Schutz, A.N., A.J., R.J.W.), the Department of Medicine (G. Meintjes, C. Stek, 
      F.T., C. Schutz, R.J.W.), and the Division of Clinical Pharmacology, Department 
      of Medicine (G. Maartens), University of Cape Town, Cape Town, South Africa; the 
      Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium 
      (C. Stek, J.B., R.R., H.L., R.C., L.L.); the Department of Internal Medicine, 
      University Hospital of Zurich, Zurich, Switzerland (F.T.); and the Department of 
      Medicine, Imperial College London and the Francis Crick Institute, London 
      (R.J.W.).
FAU - Ravinetto, Raffaella
AU  - Ravinetto R
AD  - From the Wellcome Centre for Infectious Diseases Research in Africa, Institute of 
      Infectious Disease and Molecular Medicine (G. Meintjes, C. Stek, L.B., F.T., C. 
      Schutz, A.N., A.J., R.J.W.), the Department of Medicine (G. Meintjes, C. Stek, 
      F.T., C. Schutz, R.J.W.), and the Division of Clinical Pharmacology, Department 
      of Medicine (G. Maartens), University of Cape Town, Cape Town, South Africa; the 
      Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium 
      (C. Stek, J.B., R.R., H.L., R.C., L.L.); the Department of Internal Medicine, 
      University Hospital of Zurich, Zurich, Switzerland (F.T.); and the Department of 
      Medicine, Imperial College London and the Francis Crick Institute, London 
      (R.J.W.).
FAU - van Loen, Harry
AU  - van Loen H
AD  - From the Wellcome Centre for Infectious Diseases Research in Africa, Institute of 
      Infectious Disease and Molecular Medicine (G. Meintjes, C. Stek, L.B., F.T., C. 
      Schutz, A.N., A.J., R.J.W.), the Department of Medicine (G. Meintjes, C. Stek, 
      F.T., C. Schutz, R.J.W.), and the Division of Clinical Pharmacology, Department 
      of Medicine (G. Maartens), University of Cape Town, Cape Town, South Africa; the 
      Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium 
      (C. Stek, J.B., R.R., H.L., R.C., L.L.); the Department of Internal Medicine, 
      University Hospital of Zurich, Zurich, Switzerland (F.T.); and the Department of 
      Medicine, Imperial College London and the Francis Crick Institute, London 
      (R.J.W.).
FAU - Nair, Amy
AU  - Nair A
AD  - From the Wellcome Centre for Infectious Diseases Research in Africa, Institute of 
      Infectious Disease and Molecular Medicine (G. Meintjes, C. Stek, L.B., F.T., C. 
      Schutz, A.N., A.J., R.J.W.), the Department of Medicine (G. Meintjes, C. Stek, 
      F.T., C. Schutz, R.J.W.), and the Division of Clinical Pharmacology, Department 
      of Medicine (G. Maartens), University of Cape Town, Cape Town, South Africa; the 
      Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium 
      (C. Stek, J.B., R.R., H.L., R.C., L.L.); the Department of Internal Medicine, 
      University Hospital of Zurich, Zurich, Switzerland (F.T.); and the Department of 
      Medicine, Imperial College London and the Francis Crick Institute, London 
      (R.J.W.).
FAU - Jackson, Amanda
AU  - Jackson A
AD  - From the Wellcome Centre for Infectious Diseases Research in Africa, Institute of 
      Infectious Disease and Molecular Medicine (G. Meintjes, C. Stek, L.B., F.T., C. 
      Schutz, A.N., A.J., R.J.W.), the Department of Medicine (G. Meintjes, C. Stek, 
      F.T., C. Schutz, R.J.W.), and the Division of Clinical Pharmacology, Department 
      of Medicine (G. Maartens), University of Cape Town, Cape Town, South Africa; the 
      Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium 
      (C. Stek, J.B., R.R., H.L., R.C., L.L.); the Department of Internal Medicine, 
      University Hospital of Zurich, Zurich, Switzerland (F.T.); and the Department of 
      Medicine, Imperial College London and the Francis Crick Institute, London 
      (R.J.W.).
FAU - Colebunders, Robert
AU  - Colebunders R
AD  - From the Wellcome Centre for Infectious Diseases Research in Africa, Institute of 
      Infectious Disease and Molecular Medicine (G. Meintjes, C. Stek, L.B., F.T., C. 
      Schutz, A.N., A.J., R.J.W.), the Department of Medicine (G. Meintjes, C. Stek, 
      F.T., C. Schutz, R.J.W.), and the Division of Clinical Pharmacology, Department 
      of Medicine (G. Maartens), University of Cape Town, Cape Town, South Africa; the 
      Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium 
      (C. Stek, J.B., R.R., H.L., R.C., L.L.); the Department of Internal Medicine, 
      University Hospital of Zurich, Zurich, Switzerland (F.T.); and the Department of 
      Medicine, Imperial College London and the Francis Crick Institute, London 
      (R.J.W.).
FAU - Maartens, Gary
AU  - Maartens G
AD  - From the Wellcome Centre for Infectious Diseases Research in Africa, Institute of 
      Infectious Disease and Molecular Medicine (G. Meintjes, C. Stek, L.B., F.T., C. 
      Schutz, A.N., A.J., R.J.W.), the Department of Medicine (G. Meintjes, C. Stek, 
      F.T., C. Schutz, R.J.W.), and the Division of Clinical Pharmacology, Department 
      of Medicine (G. Maartens), University of Cape Town, Cape Town, South Africa; the 
      Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium 
      (C. Stek, J.B., R.R., H.L., R.C., L.L.); the Department of Internal Medicine, 
      University Hospital of Zurich, Zurich, Switzerland (F.T.); and the Department of 
      Medicine, Imperial College London and the Francis Crick Institute, London 
      (R.J.W.).
FAU - Wilkinson, Robert J
AU  - Wilkinson RJ
AD  - From the Wellcome Centre for Infectious Diseases Research in Africa, Institute of 
      Infectious Disease and Molecular Medicine (G. Meintjes, C. Stek, L.B., F.T., C. 
      Schutz, A.N., A.J., R.J.W.), the Department of Medicine (G. Meintjes, C. Stek, 
      F.T., C. Schutz, R.J.W.), and the Division of Clinical Pharmacology, Department 
      of Medicine (G. Maartens), University of Cape Town, Cape Town, South Africa; the 
      Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium 
      (C. Stek, J.B., R.R., H.L., R.C., L.L.); the Department of Internal Medicine, 
      University Hospital of Zurich, Zurich, Switzerland (F.T.); and the Department of 
      Medicine, Imperial College London and the Francis Crick Institute, London 
      (R.J.W.).
FAU - Lynen, Lutgarde
AU  - Lynen L
AD  - From the Wellcome Centre for Infectious Diseases Research in Africa, Institute of 
      Infectious Disease and Molecular Medicine (G. Meintjes, C. Stek, L.B., F.T., C. 
      Schutz, A.N., A.J., R.J.W.), the Department of Medicine (G. Meintjes, C. Stek, 
      F.T., C. Schutz, R.J.W.), and the Division of Clinical Pharmacology, Department 
      of Medicine (G. Maartens), University of Cape Town, Cape Town, South Africa; the 
      Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium 
      (C. Stek, J.B., R.R., H.L., R.C., L.L.); the Department of Internal Medicine, 
      University Hospital of Zurich, Zurich, Switzerland (F.T.); and the Department of 
      Medicine, Imperial College London and the Francis Crick Institute, London 
      (R.J.W.).
CN  - PredART Trial Team
LA  - eng
SI  - ClinicalTrials.gov/NCT01924286
GR  - MC_U117588499/MRC_/Medical Research Council/United Kingdom
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Anti-Retroviral Agents)
RN  - 0 (Antitubercular Agents)
RN  - VB0R961HZT (Prednisone)
SB  - IM
CIN - N Engl J Med. 2019 May 2;380(18):1780-1781. PMID: 31042843
MH  - AIDS-Related Opportunistic Infections/*drug therapy
MH  - Adult
MH  - Anti-Inflammatory Agents/adverse effects/*therapeutic use
MH  - Anti-Retroviral Agents/*adverse effects/therapeutic use
MH  - Antitubercular Agents/therapeutic use
MH  - CD4 Lymphocyte Count
MH  - Double-Blind Method
MH  - Female
MH  - HIV Infections/complications/*drug therapy
MH  - Humans
MH  - Immune Reconstitution Inflammatory Syndrome/etiology/*prevention & control
MH  - Male
MH  - Prednisone/adverse effects/*therapeutic use
MH  - Tuberculosis, Pulmonary/*complications/drug therapy
EDAT- 2018/11/15 06:00
MHDA- 2018/11/27 06:00
CRDT- 2018/11/15 06:00
PHST- 2018/11/15 06:00 [entrez]
PHST- 2018/11/15 06:00 [pubmed]
PHST- 2018/11/27 06:00 [medline]
AID - 10.1056/NEJMoa1800762 [doi]
PST - ppublish
SO  - N Engl J Med. 2018 Nov 15;379(20):1915-1925. doi: 10.1056/NEJMoa1800762.