Biomarkers in an HIV-1 Infected Drug Abusing Clinical Cohort

HIV-1感染和甲基苯丙胺对中枢神经系统有破坏性影响 (CMS)。此外，药物滥用往往与针头造成的艾滋病毒-1感染有关 分享。这些患者的治疗是一个非常复杂的过程，因为它必须针对两个实体 在性质上是完全不同的。尽管做出了实质性的研究努力，但认知基础的机制 艾滋病毒-1感染或冰毒使用造成的损害远未被了解。我们假设先进的 蛋白质组学技术可能导致新的疾病标志物和对疾病过程的关键洞察。我们 假设血浆样本的蛋白质组成包含独特的蛋白质组特征 (指纹)。对停止使用冰毒的患者的此类样本进行分析将导致 识别和更好地理解可逆(短期)的分子机制 以及艾滋病毒-1感染和冰毒之间相互作用的不可逆转(长期)影响。这个 这项建议的优点在于其精心挑选和明确定义的临床材料、记录 经过验证并成功地使用创新和技术先进的“尖端”蛋白质组 方法，跨学科的研究小组，优先发展基于蛋白质组学的 生物标记物发现和功能蛋白质组学平台，独家使用所需的“尖端技术” 设备，以及强大的研究和协作环境。 目的1.确定反映短期和长期的血浆蛋白质组谱的差异 停用冰毒。这一目标的工作反映了这样的假设，即血浆中含有显著的 检测暴露于滥用药物(冰毒)的中枢神经系统HIV感染的蛋白质标志物，可用于 更好地理解潜在的分子机制。 目的2.证实未被发现的生物标志物在糖尿病的分子机制中的相关性。 HIV-1感染与冰毒使用的协同效应。这一目标的长期目标是验证 HIV和冰毒对中枢神经系统的共同作用的特异性标记物，将用于未来，更多 ‘专注于假设驱动的项目。 这项工作的公共卫生相关性涉及重叠的艾滋病毒感染者和 那些使用冰毒的人。血液中蛋白质生物标记物的发现将使研究有害的 冰毒在艾滋病毒感染环境中的作用，导致加大教育力度，改善诊断， 和治疗方面的进展。

HIV-1 infection and methamphetamine (METH) have devastating effects on the central nervous system (CMS). Moreover, drug abuse is very often associated with HIV-1 infection as a consequence of needle sharing. Treatment of these patients is a very complex process because it has to target two entities which are quite different in nature. Despite substantive research efforts, the mechanisms underlying cognitive impairment resulting from HIV-1 infection or METH use are far from understood. We posit that advances in proteomic techniques could lead to new markers of disease and critical insights into disease processes. We hypothesize that the protein composition of plasma samples contains unique proteomic signatures (fingerprints). Profiling of such samples from patients who stopped using METH will lead to identification and better understanding of molecular mechanisms underlying reversible (short-term) and non-reversible (long-term) effects of the interactions between HIV-1 infection and METH. The strengths of this proposal lie in its carefully selected and well defined cohort of clinical material, track record of a proven and successful use of innovative and technologically advanced "cutting edge" proteomic approaches, the interdisciplinary group of investigators, the prior development of proteomics-based biomarker discovery and functional proteomics platforms, the exclusive use of needed "cutting edge" equipment, and strong research and collaborative environment. Aim 1. To determine differences in proteome profiles of plasma which reflect short- and long-term withdrawal of METH. The work in this aim reflects the hypothesis that plasma contains in significant measure protein markers of HIV infection of CNS exposed to drug of abuse (METH), which could be used for better understanding of underlying molecular mechanisms. Aim 2. To substantiate the relevance of uncovered biomarkers in molecular mechanisms of the synergistic effect of HIV-1 infection and use of METH. The long-term goal of this aim is to validate iomarkers specific for concurrent effect of HIV and METH on the CNS which will be used for future, more 'focused and hypothesis driven projects. The public health relevance of this work relates to the overlapping populations of HIV infected people with those who use METH. Discovery of protein biomarkers in the blood will enable the study of the harmful effects of METH in the setting of HIV infection, leading to increased education efforts, improved diagnostics, and therapeutic inroads.