Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa.
Clin Infect Dis. 2013 Feb;56(3):450-60. doi: 10.1093/cid/cis899. Epub 2012 Oct 24.
Tuberculosis immune reconstitution inflammatory syndrome (IRIS) is a common cause of deterioration in human immunodeficiency virus (HIV)-infected patients receiving tuberculosis treatment after starting antiretroviral therapy (ART). Potentially life-threatening neurological involvement occurs frequently and has been suggested as a reason to defer ART.
We conducted a prospective study of HIV-infected, ART-naive patients with tuberculous meningitis (TBM). At presentation, patients started tuberculosis treatment and prednisone; ART was initiated 2 weeks later. Clinical and laboratory findings were compared between patients who developed TBM-IRIS (TBM-IRIS patients) and those who did not (non-TBM-IRIS patients). A logistic regression model was developed to predict TBM-IRIS.
Forty-seven percent (16/34) of TBM patients developed TBM-IRIS, which manifested with severe features of inflammation. At TBM diagnosis, TBM-IRIS patients had higher cerebrospinal fluid (CSF) neutrophil counts compared with non-TBM-IRIS patients (median, 50 vs 3 cells ×10(6)/L, P = .02). Mycobacterium tuberculosis was cultured from CSF of 15 TBM-IRIS patients (94%) compared with 6 non-TBM-IRIS patients (33%) at time of TBM diagnosis; relative risk of developing TBM-IRIS if CSF was Mycobacterium tuberculosis culture positive = 9.3 (95% confidence interval [CI], 1.4-62.2). The combination of high CSF tumor necrosis factor (TNF)-α and low interferon (IFN)-γ at TBM diagnosis predicted TBM-IRIS (area under the curve = 0.91 [95% CI, .53-.99]).
TBM-IRIS is a frequent, severe complication of ART in HIV-associated TBM and is characterized by high CSF neutrophil counts and Mycobacterium tuberculosis culture positivity at TBM presentation. The combination of CSF IFN-γ and TNF-α concentrations may predict TBM-IRIS and thereby be a means to individualize patients to early or deferred ART.
在开始抗逆转录病毒治疗（ART）后接受结核病治疗的人类免疫缺陷病毒（HIV）感染患者中，结核病免疫重建炎症综合征（IRIS）是病情恶化的常见原因。经常发生潜在危及生命的神经受累，并被认为是推迟 ART 的一个原因。
我们对 HIV 感染、未经 ART 治疗的结核性脑膜炎（TBM）患者进行了一项前瞻性研究。在就诊时，患者开始接受结核病治疗和泼尼松治疗；2 周后开始 ART。比较了发生 TBM-IRIS（TBM-IRIS 患者）和未发生 TBM-IRIS（非 TBM-IRIS 患者）的患者的临床和实验室检查结果。建立了一个逻辑回归模型来预测 TBM-IRIS。
34 例 TBM 患者中有 47%（16/34）发生了 TBM-IRIS，表现为炎症严重。在 TBM 诊断时，TBM-IRIS 患者的脑脊液（CSF）中性粒细胞计数高于非 TBM-IRIS 患者（中位数，50 与 3 细胞×10(6)/L，P =.02）。在 TBM 诊断时，15 例 TBM-IRIS 患者（94%）的 CSF 中培养出结核分枝杆菌，而非 TBM-IRIS 患者（33%）有 6 例（相对风险，TBM-IRIS 发生如果 CSF 为结核分枝杆菌培养阳性= 9.3（95%置信区间[CI]，1.4-62.2）。TBM 诊断时 CSF 中高肿瘤坏死因子（TNF）-α和低干扰素（IFN）-γ的组合预测了 TBM-IRIS（曲线下面积= 0.91[95%CI，.53-.99]）。
TBM-IRIS 是 HIV 相关 TBM 中 ART 的常见且严重的并发症，其特征是 TBM 表现时 CSF 中性粒细胞计数高且结核分枝杆菌培养阳性。CSF IFN-γ和 TNF-α浓度的组合可能预测 TBM-IRIS，从而可以个体化选择早期或延迟 ART 的患者。
