Brain Response to HAART Measured with MR Spectroscopy

描述（由申请人提供）：拟议项目的目标是使用质子（1h）磁共振波谱（MRS）系统地研究艾滋病毒相关认知障碍患者对高活性抗逆转录病毒治疗（HAART）的大脑反应的生化标志物。代谢方面的发现也将与病毒学研究和神经心理损伤指标有关。拟议研究的具体目的是：1)评估艾滋病毒相关神经认知障碍（痴呆和轻微认知运动障碍）患者接受HAART治疗前后的脑代谢物；2)将脑代谢物的变化与治疗后脑脊液和血浆HIV RNA的改变联系起来；3)评估改变治疗策略对HAART治疗失败的个体的影响，并在有组织的治疗中断后开始新的治疗方案。假设有认知障碍的HIV阳性受试者的n -乙酰天冬氨酸（NAA）浓度较低，肌糖醇和胆碱浓度高于无认知障碍的受试者，而这些变化在治疗有效降低中枢神经系统病毒载量的受试者中会变得更正常。也有假设认为，在HAART治疗后，NAP、肌肌醇和胆碱的变化与神经认知功能的变化有关。这项研究将与圣地亚哥HIV神经行为研究中心已经资助的一项名为“HIV神经认知障碍：CSF HIV RNA和趋化因子”的5年研究项目相关联（Ronald J. Ellis， PI）。这项研究将根据血浆或血浆和脑脊液病毒的耐药表型，对服用抗逆转录病毒药物治疗方案的个体进行比较。这些耐药试验将用于选择抗逆转录病毒药物，以最大限度地抑制脑脊液病毒。拟议的研究将评估64名神经认知受损的HIV感染者的脑代谢物，与40名没有神经认知障碍的HIV感染者进行比较。所有参与者将在基线、治疗后4周和治疗后12周进行核磁共振扫描。他们的HW RNA水平也将通过父母研究以相同的间隔进行评估，他们将在基线和治疗后12周接受全面的神经心理学评估。这项拟议的研究可能为在治疗期间用MRS监测脑代谢物的效用提供证据，并可能为治疗HIV相关认知功能障碍的成功或失败提供预测指标。

DESCRIPTION (provided by applicant): The goal of the proposed project is to systematically study biochemical markers of cerebral response to highly active antiretroviral treatment (HAART) in people with HIV associated cognitive impairment using proton (1 H) magnetic resonance spectroscopy (MRS). Metabolic findings will also be related to virological studies and indices of neuropsychological impairment. The specific aims of the proposed study are 1) to evaluate brain metabolites before and after treatment with HAART regimens in individuals with HIV-associated neurocognitive disorders (dementia and minor cognitive-motor disorder); 2) To relate changes in brain metabolites with alterations in CSF and plasma HIV RNA as a result of treatment; and, 3) To evaluate the effect of altering treatment strategies in those individuals who fail HAART treatment and initiate a new regimen after structured treatment interruption. It is hypothesized that concentrations of N-acetyl aspartate (NAA) will be lower, and concentrations of myo-lnositol and Choline will be higher in HIV+ participants with cognitive impairment than in those without cognitive impairment, and that these changes will become more normal in participants whose treatments are effective in reducing viral load in the CNS. It is also hypothesized that changes in NAP,, myo-lnositol, and Choline from baseline in response to HAART treatment will be related to changes in neurocognitive functioning. The study will be linked to an already funded 5-year research program at the San Diego HIV Neurobehavioral Research Center entitled "HIV Neurocognitive Disorders: CSF HIV RNA and Chemokines" (Ronald J. Ellis, PI). The study will compare individuals who are prescribed antiretroviral drug treatment regimens based on drug resistance phenotyping of plasma, or both plasma and CSF virus. These drug resistance assays will be used to select ARV agents to maximally suppress CSF virus. The proposed study will evaluate brain metabolites in 64 neurocognitively impaired HIV infected individuals, compared to 40 HIV infected individuals without neurocognitive impairment. All participants will undergo MRS scans at baseline, four weeks post-treatment, and 12 weeks post-treatment. Their HW RNA level will also be assessed at the same intervals through the parent study, and they will receive comprehensive neuropsychological evaluations at baseline and 12 weeks post-treatment. The proposed study may provide evidence for the utility of monitoring cerebral metabolites with MRS during treatment and may yield predictors of success or failure in treating HIV associated cognitive dysfunction.