Brain Response to HAART Measured with MR Spectroscopy

描述(申请人提供)：该项目的目标是利用质子(1H)磁共振波谱(MRS)系统地研究HIV相关认知障碍患者对高效抗逆转录病毒治疗(HAART)的大脑反应的生化标记物。代谢研究结果还将与病毒学研究和神经心理损伤指数相关。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(痴呆症和轻微认知运动障碍)患者接受HAART方案治疗前后的大脑代谢物；2)将大脑代谢物的变化与治疗后脑脊液和血浆HIV RNA的变化联系起来；3)评估HAART治疗失败的患者改变治疗策略的效果，并在结构化治疗中断后启动新的方案。据推测，在有认知障碍的HIV+参与者中，N-乙酰天冬氨酸(NAA)的浓度将低于无认知障碍的参与者，而肌醇和胆碱的浓度将高于无认知障碍的参与者，而在接受有效治疗减少中枢神经系统病毒负荷的参与者中，这些变化将变得更加正常。还假设HAART治疗后NAP、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为期5年的研究计划联系起来，该研究项目名为“HIV神经认知障碍：脑脊液HIV RNA和趋化因子”(Ronald J.Ellis，PI)。这项研究将比较根据血浆耐药表型或血浆和脑脊液病毒同时服用抗逆转录病毒治疗方案的个人。这些耐药性分析将被用于选择ARV药物，以最大限度地抑制脑脊液病毒。这项拟议的研究将评估神经认知受损的艾滋病毒感染者的大脑代谢物，并与40名没有神经认知障碍的艾滋病毒感染者进行比较。所有参与者都将在基线、治疗后4周和治疗后12周接受MRS扫描。他们的HW RNA水平也将通过父母研究以相同的时间间隔进行评估，并将在基线和治疗后12周接受全面的神经心理评估。这项拟议的研究可能为在治疗期间使用MRS监测大脑代谢物的有效性提供证据，并可能产生治疗HIV相关认知功能障碍成功或失败的预测因素。

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.