Although we have known for almost a decade that HIV can enter the central nervous system (CNS) soon after exposures to the virus, no """"""""gold standard"""""""" method is presently available to determine the earliest signs of infection with the human immunodeficiency virus, Type 1 (HIV) in the CNS. Metabolic and neuropsychological studies have shown that neurological abnormalities may be associated with HIV infection that are not detected with conventional neuro-imaging methods. Over the previous funding period of this project (7/1/93- present) the Investigator and his associates have implemented a protocol that utilizes magnetic resonance spectroscopy (MRS) to follow the progression of HIV infection in the CNS non-invasively. A cohort of 90 HIV seropositive patients, all of whom were initially asymptomatic, have been enrolled. This protocol was designed to test two hypotheses: (1) MRS will provide the earliest metabolic indicators of the migration of the virus into the CNS; and (2) serial MRS studies can track the time course of alterations in metabolism in individual patients and provide a metabolic basis for """"""""staging"""""""" the degree of CNS involvement over time. A major abnormality observed in the cohort is the elevation in the resonances between 2.1 and 2.6 ppm (amino acid or AA peaks) which the Investigator hypothesizes reflects early immune activation. One of the goals of this renewal is to extend the ongoing longitudinal study for three additional years as two technical developments in the researchers' laboratory may allow them to refine and expand the original hypotheses: the recent installation of a 4T research whole body MR scanner allows improved characterization of MR spectra by exploiting its inherent advantages of improved signal-to-noise ratios and increased chemical shift dispersion; the researchers have developed, validated, and implemented an ultrahigh resolution MRS method at 1.5 T which can sample selectively the metabolism of cortical gray matter and certain white matter regions. The Investigator proposes to study a new group of both symptomatic and asymptomatic patients using this method (n=30 total/year). The level of available spatial resolution makes possible initial efforts to relate the metabolic alterations observed by MRS to the pathogenesis of HIV as determined in histopathological studies. The researchers will assay two kinds of markers of disease burden based on an analysis of CSF: quantitative HIV RNA levels (a measure of viral burden) and concentrations of beta-2-microglobulin and quinolinic acid (measures of immune activation) in this newly enrolled group. The availability of these assays of disease burden will determine which of the spectral abnormalities reflect the level of immune activation and/or the viral load in the CNS.
