Adjunctive Dexamethasone for Tuberculous Meningitis in HIV-Positive Adults

被引:37
作者
Donovan, Joseph [1 ,6 ,7 ,11 ]
Bang, Nguyen D. [2 ]
Imran, Darma [8 ]
Nghia, Ho D. T. [3 ,4 ]
Burhan, Erlina [9 ]
Huong, Dau T. T. [1 ]
Hiep, Nguyen T. T. [1 ]
Ngoc, Lam H. B. [1 ]
Thanh, Dang V. [1 ]
Thanh, Nguyen T. [1 ,3 ]
Wardhani, Anna L. S. [10 ]
Maharani, Kartika [8 ]
Gasmara, Cakra P. [8 ]
Hanh, Nguyen H. H. [3 ,5 ]
Oanh, Pham K. N. [3 ]
Estiasari, Riwanti [8 ]
Thu, Do D. A. [1 ]
Kusumaningrum, Ardiana [8 ]
Dung, Le T. [2 ]
Giang, Do C. [2 ]
Ha, Dang T. M. [2 ]
Lan, Nguyen H. [2 ]
Chau, Nguyen V. V. [3 ]
Nguyet, Nguyen T. M. [1 ]
Geskus, Ronald B. [1 ,6 ]
Thuong, Nguyen T. T. [1 ,6 ]
Kestelyn, Evelyne [1 ,6 ]
Hamers, Raph L. [6 ,10 ]
Phu, Nguyen H. [1 ,5 ,6 ]
Thwaites, Guy E. [1 ,6 ]
机构
[1] Univ Oxford, Clin Res Unit, Nuffield Dept Med, Oxford, England
[2] Vietnam Natl Univ Ho Chi Minh City, Pham Ngoc Thach Hosp TB & Lung Dis, Ho Chi Minh City, Vietnam
[3] Vietnam Natl Univ Ho Chi Minh City, Hosp Trop Dis, Ho Chi Minh City, Vietnam
[4] Vietnam Natl Univ Ho Chi Minh City, Pham Ngoc Thach Univ Med, Ho Chi Minh City, Vietnam
[5] Vietnam Natl Univ Ho Chi Minh City, Sch Med, Ho Chi Minh City, Vietnam
[6] Univ Oxford, Ctr Trop Med & Global Hlth, Nuffield Dept Med, Oxford, England
[7] London Sch Hyg & Trop Med, London, England
[8] Univ Indonesia, Dr Cipto Mangunkusumo Natl Reference Hosp, Fac Med, Jakarta, Indonesia
[9] Univ Indonesia, Persahabatan Natl Resp Referral Hosp, Fac Med, Jakarta, Indonesia
[10] Oxford Univ Clin Res Unit Indonesia, Univ Indonesia, Fac Med, Jakarta, Indonesia
[11] London Sch Hyg & Trop Med, Clin Res Dept, Rm 359, Keppel St, London WC1E 7HT, England
基金
英国惠康基金;
关键词
PREDNISOLONE;
D O I
10.1056/NEJMoa2216218
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Adjunctive glucocorticoids are widely used to treat human immunodeficiency virus (HIV)-associated tuberculous meningitis despite limited data supporting their safety and efficacy.Methods We conducted a double-blind, randomized, placebo-controlled trial involving HIV-positive adults (>= 18 years of age) with tuberculous meningitis in Vietnam and Indonesia. Participants were randomly assigned to receive a 6-to-8-week tapering course of either dexamethasone or placebo in addition to 12 months of antituberculosis chemotherapy. The primary end point was death from any cause during the 12 months after randomization.Results A total of 520 adults were randomly assigned to receive either dexamethasone (263 participants) or placebo (257 participants). The median age was 36 years; 255 of 520 participants (49.0%) had never received antiretroviral therapy, and 251 of 484 participants (51.9%) with available data had a baseline CD4 count of 50 cells per cubic millimeter or less. Six participants withdrew from the trial, and five were lost to follow-up. During the 12 months of follow-up, death occurred in 116 of 263 participants (44.1%) in the dexamethasone group and in 126 of 257 participants (49.0%) in the placebo group (hazard ratio, 0.85; 95% confidence interval, 0.66 to 1.10; P=0.22). Prespecified analyses did not reveal a subgroup that clearly benefited from dexamethasone. The incidence of secondary end-point events, including cases of immune reconstitution inflammatory syndrome during the first 6 months, was similar in the two trial groups. The numbers of participants with at least one serious adverse event were similar in the dexamethasone group (192 of 263 participants [73.0%]) and the placebo group (194 of 257 participants [75.5%]) (P=0.52).Conclusions Among HIV-positive adults with tuberculous meningitis, adjunctive dexamethasone, as compared with placebo, did not confer a benefit with respect to survival or any secondary end point. (Funded by the Wellcome Trust; ACT HIV ClinicalTrials.gov number, NCT03092817.) In this randomized trial, HIV-positive adults with tuberculous meningitis were assigned to receive 6 to 8 weeks of dexamethasone or placebo in addition to tuberculosis treatment. No benefit of dexamethasone was observed.
引用
收藏
页码:1357 / 1367
页数:11
相关论文
共 27 条
[1]  
[Anonymous], 2020, WHO CONSOLIDATED GUI
[2]   Adjunctive Dexamethasone in HIV-Associated Cryptococcal Meningitis [J].
Beardsley, J. ;
Wolbers, M. ;
Kibengo, F. M. ;
Ggayi, A. -B. M. ;
Kamali, A. ;
Cuc, N. T. K. ;
Binh, T. Q. ;
Chau, N. V. V. ;
Farrar, J. ;
Merson, L. ;
Phuong, L. ;
Thwaites, G. ;
Van Kinh, N. ;
Thuy, P. T. ;
Chierakul, W. ;
Siriboon, S. ;
Thiansukhon, E. ;
Onsanit, S. ;
Supphamongkholchaikul, W. ;
Chan, A. K. ;
Heyderman, R. ;
Mwinjiwa, E. ;
van Oosterhout, J. J. ;
Imran, D. ;
Basri, H. ;
Mayxay, M. ;
Dance, D. ;
Phimmasone, P. ;
Rattanavong, S. ;
Lalloo, D. G. ;
Day, J. N. .
NEW ENGLAND JOURNAL OF MEDICINE, 2016, 374 (06) :542-554
[3]  
Donovan J., 2018, Wellcome Open Res, V3, P31, DOI 10.12688/wellcomeopenres.14006.1
[4]  
Donovan Joseph, 2021, Wellcome Open Res, V6, P280, DOI 10.12688/wellcomeopenres.17154.2
[5]   The neurocritical care of tuberculous meningitis [J].
Donovan, Joseph ;
Figaji, Anthony ;
Imran, Darma ;
Nguyen Hoan Phu ;
Rohlwink, Ursula ;
Thwaites, Guy E. .
LANCET NEUROLOGY, 2019, 18 (08) :771-783
[6]   A randomized, double-blind, placebo-controlled trial of the use of prednisolone as an adjunct to treatment in HIV-1-associated pleural tuberculosis [J].
Elliott, AM ;
Luzze, H ;
Quigley, MA ;
Nakiyingi, JS ;
Kyaligonza, S ;
Namuiju, PB ;
Ducar, C ;
Ellner, JJ ;
Whitworth, JAG ;
Mugerwa, R ;
Johnson, JL ;
Okwera, A .
JOURNAL OF INFECTIOUS DISEASES, 2004, 190 (05) :869-878
[7]   Intensified Antituberculosis Therapy in Adults with Tuberculous Meningitis [J].
Heemskerk, A. Dorothee ;
Bang, Nguyen D. ;
Mai, Nguyen T. H. ;
Chau, Tran T. H. ;
Phu, Nguyen H. ;
Loc, Pham P. ;
Chau, Nguyen V. V. ;
Hien, Tran T. ;
Dung, Nguyen H. ;
Lan, Nguyen T. N. ;
Lan, Nguyen H. ;
Lan, Nguyen N. ;
Phong, Le T. ;
Vien, Nguyen N. ;
Hien, Nguyen Q. ;
Yen, Nguyen T. B. ;
Ha, Dang T. M. ;
Day, Jeremy N. ;
Caws, Maxine ;
Merson, Laura ;
Thinh, Tran T. V. ;
Wolbers, Marcel ;
Thwaites, Guy E. ;
Farrar, Jeremy J. .
NEW ENGLAND JOURNAL OF MEDICINE, 2016, 374 (02) :124-134
[8]   Anakinra in the treatment of protracted paradoxical inflammatory reactions in HIV-associated tuberculosis in the United Kingdom: a report of two cases [J].
Keeley, Alex J. ;
Parkash, Vivak ;
Tunbridge, Anne ;
Greig, Julia ;
Collini, Paul ;
McKane, William ;
Tattersall, Rachel S. .
INTERNATIONAL JOURNAL OF STD & AIDS, 2020, 31 (08) :808-812
[9]   Use of Infliximab to Treat Paradoxical Tuberculous Meningitis Reactions [J].
Marais, Ben J. ;
Cheong, Elaine ;
Fernando, Shelanah ;
Daniel, Santhosh ;
Watts, Matthew R. ;
Berglund, Lucinda J. ;
Barry, Simone E. ;
Kotsiou, George ;
Headley, Alex P. ;
Stapledon, Richard A. .
OPEN FORUM INFECTIOUS DISEASES, 2021, 8 (01)
[10]   Frequency, Severity, and Prediction of Tuberculous Meningitis Immune Reconstitution Inflammatory Syndrome [J].
Marais, Suzaan ;
Meintjes, Graeme ;
Pepper, Dominique J. ;
Dodd, Lori E. ;
Schutz, Charlotte ;
Ismail, Zahiera ;
Wilkinson, Katalin A. ;
Wilkinson, Robert J. .
CLINICAL INFECTIOUS DISEASES, 2013, 56 (03) :450-460