Endotoxin Neutralization as a Biomonitor for HIV Disease Progression

描述（由申请人提供）：人血浆内毒素中和是慢性免疫激活的一个极好的指标，它是HIV死亡率的最准确预测指标。最近，我们开发了一种检测方法，使用内毒素中和作为细菌易位的指标。除了表明疾病的严重程度外，该检测还可以准确地区分对照组患者和炎症性肠病患者。我们建议将我们的内毒素中和试验用于评估HIV疾病的严重程度和进展。在为期6个月的SBIR项目I期部分中，我们将(1)收集20名19-50岁的hiv阳性男性和同等数量的人口统计学相似的hiv阴性男性受试者的血浆，并检测病毒载量和CD4+ T细胞计数，(2)测量指示细菌易位，免疫系统激活和/或炎症反应的特定血浆标志物水平，以及(3)使用我们的内毒素中和生物标志物监测系统测量免疫激活。一旦建立了每个样品的中和剖面，Pearson相关性将用于确定内毒素中和与前两个目标中建立的所有因素之间的关系。学生t检验将用于确定HIV阳性组和对照组之间的统计显著性。第一阶段的结果将显示我们的内毒素中和系统是否是一种方便、可重复和廉价的方法来评估HIV疾病的严重程度。在项目的第二阶段，我们将使用我们的系统在1-2年的时间内监测患者，以将内毒素中和与治疗联系起来。

DESCRIPTION (provided by applicant): Endotoxin neutralization in human plasma is an excellent indicator of chronic immune activation, which is the most accurate predictor of mortality in HIV. Recently we developed an assay using endotoxin neutralization as an indicator of bacterial translocation. This assay is accurate in discriminating control patients from those with inflammatory bowel disease in addition to indicating disease severity. We propose to adapt our endotoxin neutralization assay for the evaluation of HIV disease severity and progression. In the 6 month Phase I part of the SBIR project, we will (1) collect plasma from 20 19-50 year old HIV-positive males and an equivalent number of demographically similar HIV-negative male subjects and test for viral load and CD4+ T cell count, (2) measure the levels of specific plasma markers indicative of bacterial translocation, immune system activation and/or inflammatory response, and (3) measure immune activation using our endotoxin neutralization biomarker monitor system. Once a neutralization profile of each sample is established, Pearson correlation will be used to determine the relationship between endotoxin neutralization and all factors established in the first two aims. Student's T-test will be used to determine statistical significance between HIV- positive and control groups. The results from Phase I will show whether our endotoxin neutralization system is a convenient, reproducible and inexpensive method to assess the severity of HIV disease. In Phase II of the project, we will use our system to monitor patients over a 1-2 year period to correlate endotoxin neutralization with treatment.