In vivo proton MRS studies:cerebral injury in HIV infection

体内质子 MRS 研究：HIV 感染引起的脑损伤

• 批准号: 7163125
• 负责人: BRADFORD NAVIA
• 金额: $ 101.84万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7163125
• 关键词: vivo; proton; MRS; studies; cerebral

DESCRIPTION (provided by applicant): Highly active antiretroviral therapy (HAART) has resulted in a marked rise in survival among HIV-infected persons. To what extent the brain compartment truly benefits from such treatment, particularly in the setting of advanced, even stable disease, remains unclear. The frequency, spectrum and extent of neurological injury, its relationship to cognitive functioning and responsiveness to antiretroviral therapies thus remain important yet unresolved issues. The HIV MRS consortium has identified regional and cellular abnormalities specific to different stages of HIV-associated cognitive impairment (AIDS dementia complex, ADC) as well as an in vivo model of brain injury that suggests basal ganglia and neuronal events are critical to the development of ADC. It has also identified potential host(plasma MCP-1, CSF IP-10) and viral factors (SCF HIV RNA) at baseline that may increase the risk for cognitive impairment or further decline. This application proposes a longitudinal multicenter study to examine the pattern and dynamics of regional injury by MRS and Morphometry among neurologically asymptomatic (NA) and ADC subjects with advanced disease (nadir CD4<50/ml) in relationship to cognitive performance and to identify virological and immunological events in the CSF and peripheral compartments that may contribute to neurological impairment in the setting of HAART. We will accrue 180-200 subjects (125-135 NA subjects and 55-65 ADC subjects) from two cohorts: 120-140 subjects from ACTG 362 (85-95 NA and 35-45 ADC subjects), previously immune reconstituted on HAART, and 60 subjects from the UCLA NNAB and UCSD CNTC (40 NA subjects and 20 ADC subjects) divided into virologically suppressed and not suppressed groups. The primary aims are: 1) to identify NA subjects at risk for brain injury as measured by MRS, and examine host and viral factors at baseline that may increase the risk for subsequent neurological injury; 2) to determine whether the emergence of basal ganglia and neuronal factors over time is a predictor of cognitive impairment; 3) to examine the impact of changing virologic and immunologic factors in addition to the effects of hepatitis C exposure and aging on CNS function; and 4) to determine the brain morphometric signatures (caudate, white matter and whole brain) associated with each stage of cognitive impairment and the relationship between changes in regional volumes to MRS patterns of brain injury and indices of disease activity . Longitudinal and regression statistical models will be used to study the neurological effects of HIV-infection brain as a dynamic system of interrelated factors. At a mechanistic level, the study aims to elucidate in vivo the development of brain injury and identify host and viral factors that may contribute to its risk. Detection of brain injury among NA subjects on HAART and at risk for ADC will have critical ramifications for overall health outcome and early therapeutic intervention.

描述（由申请人提供）： 高效抗逆转录病毒疗法显著提高了艾滋病毒感染者的存活率。在何种程度上，脑区室真正受益于这种治疗，特别是在先进的，甚至稳定的疾病，仍然不清楚。因此，神经系统损伤的频率、范围和程度、其与认知功能的关系以及对抗逆转录病毒疗法的反应性仍然是重要但尚未解决的问题。HIV MRS联盟已经确定了特定于不同阶段的HIV相关认知障碍（AIDS痴呆综合征，ADC）的区域和细胞异常，以及脑损伤的体内模型，表明基底神经节和神经元事件对ADC的发展至关重要。 它还确定了可能增加认知障碍或进一步下降风险的潜在宿主（血浆MCP-1，CSF IP-10）和病毒因子（SCF HIV RNA）。 本申请提出了一项纵向多中心研究，旨在通过MRS和形态测定法检查神经系统无症状（NA）和晚期疾病（最低CD 4 <50/ml）ADC受试者的局部损伤模式和动力学与认知能力的关系，并确定CSF和外周隔室中可能导致HAART背景下神经功能缺损的病毒学和免疫学事件。我们将招募180-200名受试者（125-135例NA受试者和55-65例ADC受试者）：ACTG 362中的120-140例受试者（85-95名NA和35-45名ADC受试者），先前在HAART上免疫重建，来自UCLA NNAB和UCSD CNTC的60名受试者（40名NA受试者和20名ADC受试者）被分为病毒学抑制组和非抑制组。 主要目标是：1）鉴定如通过MRS测量的处于脑损伤风险的NA受试者，并在基线检查可能增加随后神经损伤风险的宿主和病毒因素; 2）确定基底神经节和神经元因素随时间的出现是否是认知障碍的预测因子; 3）除了丙型肝炎暴露和衰老对CNS功能的影响外，还检查变化的病毒学和免疫学因素的影响;以及4）确定与认知损害的每个阶段相关的脑形态测量特征（尾状核、白色物质和全脑）以及脑损伤的MRS模式的区域体积变化与疾病活动指数之间的关系。纵向和回归统计模型将被用来研究HIV感染的大脑作为一个动态系统的相互关联的因素的神经系统的影响。 在机制水平上，该研究旨在阐明体内脑损伤的发展，并确定可能导致其风险的宿主和病毒因素。 在接受HAART和ADC风险的NA受试者中检测脑损伤将对整体健康结局和早期治疗干预产生重要影响。