MR PREDICTORS OF RESPONSE TO HAART IN HIV DEMENTIA

描述（申请人摘要）：最常见和最令人衰弱的 HIV感染的神经系统并发症是HIV痴呆（HIVD）或艾滋病 痴呆综合征（ADC）。这种疾病的确切发病机制仍然是一个 难题然而，CNS中单核吞噬细胞（MP）的感染， 神经营养因子的正常合成、释放 神经毒性病毒蛋白和炎症因子的释放， 强烈暗示了这一事件的发生齐多夫定单药治疗， 最近，高效抗逆转录病毒疗法（HAART） 降低HIVD的发病率。齐多夫定或HAART可能会阻止或 甚至扭转痴呆的过程，至少暂时，在许多但不是全部， 患者HAART可能减缓HIVD进展的方法是 不清楚在这项研究中，采用了不同严重程度的HIVD患者， 通过临床检查，神经心理学测试， 磁共振波谱（MRS）和对比增强磁共振 通过MRI，我们提出了以下假设：1）特异性 导致HIVD的致病途径具有不同的MR特征; 2）这些 不同的途径对HAART具有不同的敏感性; 3）MR特征 将预测HAART治疗HIVD的有效性。确认这些 假设将有助于验证MR作为不同途径的有价值探针 HIVD的发病机制。它还将为探索 这些途径对HAART的敏感性差异，并表明独特的 治疗选择

DESCRIPTION (Applicant's abstract): Among the most common and debilitating neurological complications of HIV infection is HIV dementia (HIVD) or AIDS dementia complex (ADC). The exact pathogenesis of this disorder remains a conundrum. However, infection of mononuclear phagocytes (MP) in the CNS, and the consequent inhibition of normal synthesis of neurotrophic factors, release of neurotoxic viral proteins and release of inflammatory factors, has been strongly implicated as the precipitating event. Zidovudine monotherapy and, more recently, highly active antiretroviral therapy (HAART) have both been postulated to reduce the incidence of HIVD. Zidovudine or HAART may arrest or even reverse the dementing process, at least temporarily, in many but not all patients. The means by which HAART might slow the progression of HIVD is unclear. In this study employing patients with HIVD of varying severity, carefully studied by clinical examination, neuropsychological test battery, magnetic resonance spectroscopy (MRS) and contrast-enhanced magnetic resonance imaging (MRI), we propose to test the following hypotheses: 1) specific pathogenic pathways leading to HIVD have distinct MR signatures; 2) these different pathways have different sensitivities to HAART; 3) the MR signature will predict the effectiveness of HAART in treating HIVD. Confirmation of these hypotheses will help to validate MR as a valuable probe of different pathways of HIVD pathogenesis. It will also open novel avenues for exploring the differential sensitivities of these pathways to HAART, and suggest unique therapeutic options.