HIV Neuropathogenesis in a Cohort of Long-Term Surviving Young Adults in Romania

描述(由申请人提供)：慢性神经心理损伤(NPI)是接受抗病毒治疗(HAART)的HIV感染长期幸存者的主要并发症。发病机制尚不清楚，但可能的候选因素有：神经毒性病毒蛋白；药物副作用；行为风险因素(如药物滥用)；伴随神经胶质细胞激活的慢性炎症；患者遗传背景，可能调节对感染的代谢和内分泌反应；年龄；性别；以及特定的机会性病理。我们现在已经在布加勒斯特的维克多婴儿医院(VBH)确定了一个独特的患者队列，这可能有助于破译与长期艾滋病毒感染相关的一些特定的NP风险因素。这些患者是唯一有资格进行纵向研究的患者：他们形成了一个高度同质性的队列(平均18岁)。对于类似的病毒株感染(分支F)，HAART方案(约.7年)和遗传背景。我们将汇集75名受试者(25名HIV+伴NPI，25名HIV+非NPI，25名HIV-)，通过常规的神经内科和NP检查以及对疾病的血清学和脑脊液(CSF)标志物的临床实验室评估，进行为期两年的研究。为了测量NPI，我们将使用加州大学圣地亚哥分校HIV神经行为研究中心(HNRC)开发的测试电池。具体目标1：展示一套全面的神经心理学(NP)测试组合在罗马尼亚的跨文化适用性，该测试组合已被广泛验证，用于检测和表征美国HIV-1感染的神经行为影响。具体目标2：确定罗马尼亚年轻人感染艾滋病毒的共病因素，并将它们与NPI的程度进行比较。具体目标#3：表征罗马尼亚F分支艾滋病毒的神经毒性潜力及其对抗病毒治疗的敏感性。该项目将证明可行性，并将有助于在罗马尼亚建立进行神经行为和病毒学研究的基础设施，罗马尼亚尚未对艾滋病毒-1的神经认知表现进行系统研究。罗马尼亚的队列可以为HIV相关NPI的未来提供独特的洞察力-HAART的幸存者。

DESCRIPTION (provided by applicant): Chronic neuropsychologic impairment (NPI) is a major complication in HIV infected long-term survivors on antiviral therapy (HAART). The pathogenesis is still unknown but likely candidates are: neurotoxic viral proteins; pharmacologic side effects; behavioral risk factors (e.g. drug abuse); chronic inflammation accompanied by neuroglial activation; the patient genetic background potentially modulating the metabolic and endocrinologic response to infection; age; gender; and also specific opportunistic pathologies. We have now identified a unique patient cohort at the Victor Babes Hospital (VBH) in Bucharest that may help in deciphering some of the specific NP risk factors associated with long term HIV infection. These patients are uniquely qualified for a longitudinal study: they form a highly homogenous cohort (average 18 y. o.) with similar viral strain infection (clade F), HAART regimen (approx. 7 years), and genetic background. We will assemble a cohort of 75 subjects (25 HIV+ with NPI, 25 HIV+ without NPI, and 25 HIV-) that will be studied for 2 years through regular neuromedical and NP exams and clinical laboratory evaluations of serologic and cerebrospinal fluid (CSF) markers of disease. To measure NPI we will use a test battery developed at the HIV Neurobehavioral Research Center (HNRC) at UC San Diego. Specific Aim #1: Demonstrate the cross-cultural applicability in Romania of a comprehensive neuropsychological (NP) test battery that has been extensively validated for detecting and characterizing neurobehavioral effects of HIV-1 infection in the U.S. Specific Aim #2: Identify comorbid factors in the Romanian young adults with HIV and compare them to the degree of NPI. Specific Aim #3: Characterize the neurotoxic potential of the Romanian clade F HIV and its susceptibility to antiviral treatments. This project will demonstrate feasibility and will help develop an infrastructure to perform neurobehavioral and virological studies in Romania, where no systematic studies of the neurocognitive manifestations of HIV-1 have been performed. The Romanian cohort could provide a unique insight in the future of HIV- associated NPI in long term-survivors on HAART.