Brain Response to HAART Measured with MR Spectroscopy

超出所提供的空间。该项目的目标是使用质子（1H）磁共振光谱（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。该研究的具体目的是：1)评估不同抗逆转录病毒治疗方案对hiv相关神经认知障碍（痴呆和轻度认知运动障碍）患者治疗前后的脑代谢物；2)将脑代谢物的变化与抗逆转录病毒治疗后脑脊液和血浆中HIV RNA的变化联系起来；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阳性参与者的n -乙酰天冬氨酸（NAA）浓度会比没有认知障碍的参与者低，肌肌肽和胆碱的浓度会更高，并且这些变化会在治疗有效降低中枢神经系统病毒载量的参与者中变得更正常。也有假设认为，在HAART治疗后，naa、肌醇和胆碱的基线变化与神经认知功能的变化有关。该研究将与圣地亚哥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。埃利斯,π)。该研究将根据血浆或血浆和csf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能最大限度地抑制scsf病毒的抗逆转录病毒药物。这项拟议的研究将评估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gomrs扫描。他们的hiv RNA水平也将在母体研究中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。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，并可能产生治疗HIV相关认知功能障碍表现的后续失败的预测因子

EXCEED THE SPACE PROVIDED. Thegoal of the proposedproject is to systematicallystudy biochemical markersof cerebralresponseto highlyactive antiretroviraltreatment (HAART) in people with HIV associated cognitive impairment usingproton(1H)magnetic resonancespectroscopy(MRS).Metabolicfindingswill also be related to virologicalstudiesand indices of neuropsychologicalimpairment.The specificaimsof the proposed study are 1)to evaluatebrain metabolitesbefore and aftertreatmentwithdifferent antiretroviraltreatment regimensin individualswith HIV-associatedneurocognitive disorders (dementiaand minorcognitive-motordisorder);2) To relate changesin brain metabolites with alterationsin HIV RNA collected from the CSF andplasma as a result of antiretroviraltreatment; and, 3) To evaluatethe effect of alteringtreatmentstrategiesin those individualswho fail HAART treatment and initiatea new regimenafter structuredtreatmentinterruption.It is hypothesizedthat concentrationsof N-acetylaspartate(NAA)will be lower, and concentrationsof myo-InositolandCholinewill be higher in HIV+ participantswith cognitiveimpairmentthan in thosewithoutcognitive impairment, andthat these changeswill become more normalin participantswhose treatments are effective in reducingviral load in the CNS. It is alsohypothesizedthat changesinNAA,myo-Inositol, and Cholinefrombaseline in responseto HAART treatment will be related to changesin neurocognitivefunctioning.The studywill be linkedto an already funded5-yearresearch program at the SanDiegoHIV NeurobehavioralResearch Center entitled "HIVNeurocognitiveDisorders:CSF HIV RNA and Chemokines" (RonaldJ. Ellis, PI). The studywill compareindividualswho are prescribed antiretroviraldrugtreatmentregimensbased on drugresistancephenotyping of either plasma,or both plasma andCSFvirus. Thesedrug resistanceassayswill be usedto selectARV agentsto maximallysuppressCSFvirus. Theproposedstudy will evaluate brain metabolitesin 64 neurocognitivelyimpaired HIV infected individuals,compared to 40 HIV infected individualswithout neurocognitiveimpairment. All participantswill undergoMRS scans at baseline, four weeks post-treatment,and 12weekspost-treatment. TheirHIV RNA level will also be assessedat the sameintervals throughthe parent study, andthey will receive comprehensive neuropsychologicalevaluationsat baseline and 12weekspost-treatment.The proposed studymay provide evidence for the utility of monitoringcerebralmetaboliteswith MRS during treatment andmay yield predictors of successor failure in treating HIV associatedcognitivedysfunction PERFORMANCESITE@ ========================================Section End===========================================