An evaluation of neurocognitive status and markers of immune activation as predictors of time to death in advanced HIV infection
An evaluation of neurocognitive status and markers of immune activation as predictors of time to death in advanced HIV infection
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DOI：
10.1001/archneur.64.1.97
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发表时间：
2007-01-01
影响因子：
--
通讯作者：
Epstein, Leon G.
中科院分区：
文献类型：
--
作者：
Sevigny, Jeffrey J.;Albert, Steven M.;Epstein, Leon G.
背景资料：几种免疫激活标志物已被确定为人类免疫缺陷病毒（HIV）相关发病率和死亡率的潜在预后标志物，但研究结果相互矛盾。目的：评估神经认知状态和基线水平的血浆和脑脊液肿瘤坏死因子α（肿瘤坏死因子-α）、巨噬细胞趋化蛋白1（MCP-1）、基质金属蛋白酶2（MMP-2）或巨噬细胞集落刺激因子（M-CSF）与晚期HIV感染队列的死亡时间相关。设计：队列研究。设置：参加东北艾滋病痴呆研究的人。参与者：329例HIV-1阳性且CD 4细胞计数低于200/mu L的受试者（或< 300/μ L但在基线时有认知障碍）评估CD 4细胞计数、神经认知状态、相关人口统计学和临床变量以及血浆和脑脊液HIV RNA、TNF-α、MCP-1、MMP-2，和M-CSF水平。主要结果测量：考克斯比例风险回归模型被用来检查相关变量（使用时间依赖的协变量，在适用的情况下）和死亡时间之间的关联，调整可能的混杂因素。1年时的累积死亡率为7%，2年时为16%。在调整人口统计学、临床和免疫学变量的考克斯比例风险回归分析中，（风险率，6.10; P=.001）与死亡时间显著相关;（log）血浆MCP-1水平（风险率，3.38; P= 0.08）趋于显著性。在晚期HIV感染患者中，HIV相关性痴呆是死亡时间的独立预测因子。
Background: Several markers of immune activation have been identified as potential prognostic markers for human immunodeficiency virus (HIV)-associated morbidity and mortality, but the results from studies are conflicting.Objective: To evaluate whether neurocognitive status and baseline levels of plasma and cerebrospinal fluid tumor necrosis factor alpha (TNF-alpha), macrophage chemoattractant protein 1 (MCP-1), matrix metalloproteinase 2 (MMP-2), or macrophage colony-stimulating factor (M-CSF) are associated with time to death in a cohort with advanced HIV infection.Design: Cohort study.Setting: Enrollees in the Northeast AIDS Dementia Study.Participants: Three hundred twenty-nine subjects who were positive for HIV-1 and had a CD4 cell count of less than 200/mu L (or < 300/mu L but with cognitive impairment at baseline) were assessed for CD4 cell count, neurocognitive status, pertinent demographic and clinical variables, and plasma and cerebrospinal fluid HIV RNA, TNF-alpha, MCP-1, MMP-2, and M-CSF levels.Main Outcome Measures: Cox proportional hazards regression models were used to examine the associations between the variables of interest (using time-dependent covariates, where applicable) and time to death, adjusting for possible confounders.Results: There were 50 deaths in the cohort after a median of 25.2 months of follow-up. The cumulative incidences of death were 7% at 1 year and 16% at 2 years. In Cox proportional hazards regression analyses adjusting for demographic, clinical, and immunological variables, HIV-associated dementia (hazard rate, 6.10; P=.001) was significantly associated with time to death; (log) plasma MCP-1 level (hazard rate, 3.38; P=.08) trended toward significance.Conclusion: In patients with advanced HIV infection, HIV-associated dementia is an independent predictor of time to death.