HIV 阳性成人结核性脑膜炎的辅助性地塞米松治疗。
Adjunctive Dexamethasone for Tuberculous Meningitis in HIV-Positive Adults.
机构信息
From the Oxford University Clinical Research Unit (J.D., D.T.T.H., N.T.T.H., L.H.B.N., D.V.T., N.T.T., D.D.A.T., N.T.M.N., R.B.G., N.T.T.T., E.K., N.H.P., G.E.T.), Pham Ngoc Thach Hospital for Tuberculosis and Lung Disease (N.D.B., L.T.D., D.C.G., D.T.M.H., N.H.L.), the Hospital for Tropical Diseases (H.D.T.N., N.T.T., N.H.H.H., P.K.N.O., N.V.V.C.), Pham Ngoc Thach University of Medicine (H.D.T.N.), and the School of Medicine, Vietnam National University of Ho Chi Minh City (N.H.H.H., N.H.P.) - all in Ho Chi Minh City, Vietnam; the Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford (J.D., R.B.G., N.T.T.T., E.K., R.L.H., N.H.P., G.E.T.), and London School of Hygiene and Tropical Medicine, London (J.D.) - both in the United Kingdom; and Dr. Cipto Mangunkusumo National Reference Hospital (D.I., K.M., C.P.G., R.E., A.K.), Persahabatan National Respiratory Referral Hospital (E.B.), and Oxford University Clinical Research Unit Indonesia (A.L.S.W., R.L.H.), Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
出版信息
N Engl J Med. 2023 Oct 12;389(15):1357-1367. doi: 10.1056/NEJMoa2216218.
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.).
背景
尽管有有限的数据支持其安全性和疗效，但辅助糖皮质激素仍被广泛用于治疗人类免疫缺陷病毒（HIV）相关性结核性脑膜炎。
方法
我们在越南和印度尼西亚进行了一项双盲、随机、安慰剂对照试验，纳入了 HIV 阳性成人（≥18 岁）结核性脑膜炎患者。参与者被随机分配接受为期 6-8 周的递减疗程地塞米松或安慰剂，外加 12 个月的抗结核化疗。主要终点是随机分组后 12 个月内任何原因导致的死亡。
结果
共有 520 名成年人被随机分配接受地塞米松（263 名参与者）或安慰剂（257 名参与者）治疗。中位年龄为 36 岁；520 名参与者中有 255 名（49.0%）从未接受过抗逆转录病毒治疗，484 名有基线 CD4 计数数据的参与者中有 251 名（51.9%）的基线 CD4 计数为 50 个细胞/立方毫米或更低。6 名参与者退出了试验，5 名参与者失访。在 12 个月的随访期间，地塞米松组 263 名参与者中有 116 名（44.1%）死亡，安慰剂组 257 名参与者中有 126 名（49.0%）死亡（风险比，0.85；95%置信区间，0.66 至 1.10；P=0.22）。预先指定的分析并未发现明确受益于地塞米松的亚组。两组试验中，包括前 6 个月免疫重建炎症综合征在内的次要终点事件的发生率相似。地塞米松组（263 名参与者中的 192 名[73.0%]）和安慰剂组（257 名参与者中的 194 名[75.5%]）至少发生 1 次严重不良事件的参与者人数相似（P=0.52）。
结论
在 HIV 阳性结核性脑膜炎成人中，与安慰剂相比，辅助地塞米松治疗并未带来生存或任何次要终点的获益。（由威康信托基金会资助；ACT HIV 临床试验。gov 编号，NCT03092817。）
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