Leukoencephalopathy in HAART-treated HIV-1+ Patients

HAART 治疗的 HIV-1 患者的白质脑病

• 批准号: 6656763
• 负责人: PASQUALE FERRANTE
• 金额: $ 12.5万
• 依托单位: FONDAZIONE DON CARLO GNOCCHI ONLUS
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6656763
• 关键词: AIDS /HIV neuropathy; AIDS therapy; HIV infections; T lymphocyte; cellular immunity; cerebrospinal fluid; clinical research; cytokine; enzyme linked immunosorbent assay; gene expression; human subject; human therapy evaluation; laser capture microdissection; longitudinal human study; magnetic resonance imaging; microarray technology; neuroimaging; neuropsychological tests; patient oriented research; polymerase chain reaction; progressive multifocal leukoencephalopathy

DESCRIPTION (provided by applicant): The advent of highly active antiretroviral therapy (HAART) has dramatically decreased the death rate due to HIV-1 infection in AIDS patients. However, the efficacy of HAART on HIV-1 associated complication of the central nervous system has remained at a lower level. Most notably, the incidence of white matter disease such as Progressive Multifocal Leukoencephalopathy (PML) appears to be less affected. Some studies show that only half of the PML patients benefit from HAART and show improved survival. Alarmingly, with the advent of HAART, PML remains a fast progressing disease in some patients, whereas other groups of patients show signs of PML with a slower progression. In addition, several new cases of anew leukoencephalopathy with no sign of active JCV replication, named non-determined leukoencephalopathy (NDLE), have been clinically diagnosed among AIDS patients under HAART treatment. In this R21 pilot research proposal, we will perform comprehensive longitudinal clinical, virological, and immunological studies on several AIDS patients under HAART exhibiting leukoencephalopathy to determine if a new variant of JCV is associated with slower progressing PML and if the new leukoencephalopathy is the result of imbalanced expression of cytokines and immunomodulators. The use of DNA microarray technology will provide us with compelling information on the profile of cellular gene expression in immune cells of AIDS patients with fast and slow progressing PML, as well as those exhibiting NDLE.

描述（由申请人提供）：高度活跃的抗逆转录病毒疗法（HAART）的出现大大降低了艾滋病患者HIV-1感染引起的死亡率。但是，HAART对HIV-1相关的中枢神经系统并发症的功效保持较低水平。最值得注意的是，白质疾病的发病率，例如进行性多灶性白细胞病（PML）似乎受到的影响较小。一些研究表明，只有一半的PML患者从HAART中受益并显示出改善的生存率。令人震惊的是，随着HAART的出现，PML在某些患者中仍然是一种快速发展的疾病，而其他患者组显示出较慢进展的PML迹象。此外，在HAART治疗下，在AIDS患者中临床诊断出了几种新的白细胞脑病病例，没有活跃的JCV复制迹象，称为未确定的白细胞症（NDLE）。在这项R21试点研究建议中，我们将对HAART领导下的几名艾滋病患者进行全面的纵向临床，病毒学和免疫学研究，以表现出白细胞肾上腺病，以确定JCV的新变体是否与较慢的PML相关，以及新的白细胞肾上腺素是否与新的白细胞状态相关，是否是Cytokines和Immunododator and Immunoodulator and Immunoodulator的结果。 DNA微阵列技术的使用将为我们提供有关快速和缓慢进展PML以及表现出NDLE的AIDS免疫细胞中细胞基因表达的特征的引人注目的信息。