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 痴呆症(ADC)。这种疾病的确切发病机制仍然是 难解之谜。然而，中枢神经系统中单核吞噬细胞(MP)的感染，以及 随之而来的对神经营养因子正常合成、释放的抑制 神经毒性病毒蛋白和炎症因子的释放，已经被 与引发事件有强烈的牵连。齐多夫定单一疗法和， 最近，高效抗逆转录病毒疗法(HAART)已经 假设可以减少HIVD的发生率。齐多夫定或HAART可能会逮捕或 甚至逆转了精神错乱的过程，至少是暂时的，在许多但不是所有的情况下 病人。HAART可能减缓HIVD进展的方法是 不清楚。在这项研究中，使用了不同严重程度的HIVD患者， 通过临床检查，神经心理测试组合， 磁共振波谱(MRS)和增强磁共振 成像(MRI)，我们建议检验以下假设：1)特异性 导致HIVD的致病途径具有明显的MR特征；2)这些 不同途径对HAART的敏感性不同；3)MR信号 将预测HAART治疗HIVD的有效性。对这些的确认 假说将有助于验证MR作为不同途径的有价值的探查 HIVD的发病机制。它还将为探索 这些通路对HAART的不同敏感性，并提示 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.