Health Disparities & sCD40L: Novel Biomarkers for HIV-1 Disease Progression

全世界约有4000万人患有人类免疫缺陷病毒（HIV）-I疾病和相关疾病。 获得性免疫缺陷综合症（艾滋病），一半是妇女。受艾滋病毒/艾滋病影响的妇女超过 在过去的二十年里，任何其他疾病。有色人种女性，尤其是非裔美国人和西班牙裔 美国女性承受着这种疾病的最大负担。显然，少数群体和 妇女将继续是一个重大负担，也是健康差距研究的一个关键领域。重要的是， 几乎50%的HIV/AIDS患者患有某种神经认知损害。因此，研究涉及到 鉴定预测疾病进展和神经认知损害的新生物标志物是至关重要的。 最近的数据表明，sCD 40 L，一种新的生物标志物，在HIV感染患者中显著升高 神经认知障碍然而，没有关于sCD 40 L变化模式的信息 在种族和性别方面。这一点很重要，因为艾滋病毒/艾滋病中疾病特征的表现可能是 种族和/或性别特定。病毒载量、代谢参数和身体成分、血脂水平 等在特定种族和性别的设置上有所不同。在本申请中，我们提出研究 SCD 40 L作为HIV-1神经系统表现中疾病进展的预后标志物 种族和性别。虽然仅限于评估种族和性别作为统计风险因素， 将基础科学与健康差距相关问题结合起来。具体来说，我们将识别和分析 HIV+/-患者队列中的血浆sCD 40 L水平，并将其与标准疾病变量相关联， 认知功能所有参数将相互关联，并与神经认知测量结果相关联， 检验sCD 40 L水平与种族背景下的神经认知障碍相关的假设， 性别.我们还将分析不同患者白细胞的免疫激活状态。sCD 40 L和 将分析包括TNF-α的其它促炎细胞因子。我们的研究将是第一个完全 描述与特定认知结果相关的HIV-1阳性人群特征， 社会经济阶层和sCD 40 L，并将可能提供数据，将有直接的治疗意义。

Woridwide, -40 million people live with Human Immunodeficiency Virus (HIV)-I disease and associated Acquired Immune Deficiency Syndrome (AIDS), half are women. HIV/AIDS has affected more women than any other disease over the past two decades. Women of color, particularly, African American and Hispanic American women carry the most significant burden of this disease. Clearly, HIV/AIDS in minorities and women will continue to be a significant burden and a critical area of Health Disparities research. Importantly, almost 50% of HIV/AIDS patients suffer from some neurocognitive impairment. Thus, studies that pertain to identification of novel biomarkers that predict disease progression and neurocognitive impairment are critical. Recent data demonstrate that sCD40L, a novel biomarker is significantly elevated in HIV-infected patients with neurocognitive impairment. However, no information is available regarding patterns of sCD40L changes in context of race and gender. This is important, as expression of disease characteristics in HIV/AIDS can be race- and/or gender-specific. Viral loads, metabolic parameters and body composition, plasma lipid levels etc. differ in the setting of specific race and gender. In this application, we propose to investigate the role of SCD40L as a prognostic marker for disease progression in HIV-1 neurological manifestations in the context of race and gender. Although limited to evaluations of race and gender as statistical risk factors, this work will synergize basic science with issues related to health disparities. Specifically, we will identify and analyze plasma sCD40L levels in a cohort of HIV+/- patients and correlate these to standard disease variables and cognitive function. All parameters will be correlated with each other and against neurocognitive measures to test the hypothesis that sCD40L levels correlate with neurocognitive impairment in the context of race and gender. We will also analyze the immune activation status of diverse patient leukocytes. Levels of sCD40L & other proinflammatory cytokines including TNF-a will be analyzed. Ours will be one ofthe first studies to fully describe the HIV-1-positive population characteristics in relation to specific cognitive outcomes, socioeconomic strata and sCD40L and will likelv vield data that will have direct therapeutic implications.