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 specificaims of 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===========================================
