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. ? ? ?
