A clearer understanding of risk factors for brain injury in early HIV infection is critical for rational intervention and neuroprotection efforts. Quantitative Magnetic Resonance (MR) Imaging methodologies can be used to generate objective measurements of the brain at different levels of analysis. This investigation will exploit these noninvasive technologies to systematically quantify brain injury in HIV patients in early stages of infection in order to identify factors associated with increased risk of neurological progression. The focus of this investigation concerns activated monocytes in the peripheral circulation and factors that influence monocyte trafficking (TNFa and MCP-1, in plasma, CSF). Immunologic (CD4+ and CD8+) and virologic (HIV RNA in plasma, CSF) factors will also be evaluated. These potential determinants of neurological progression will be evaluated for patterns of relationship to objective measurements of brain injury and cognitive impairment in HIV patients in early (within 6 months of seroconversion) and asymptomatic HIV infection. All subjects will be evaluated at baseline and at a follow-up assessment, two years post-baseline. Automated segmentation algorithms will be used to derive volume fractions of the normalized brain parenchyma and of specific tissue classes (gray matter, white matter and CSF). Diffusion Tensor Imaging (DTI) will be used to measure microstructural changes in the whole brain and in specific regions that are vulnerable to injury in HIV patients, including the basal ganglia and deep white matter. The bone marrow will also be interrogated with quantitative MR methodologies. The latter imaging studies are motivated by evidence that immune activation in the marrow influences monocyte trafficking to the brain, as well as HIV replication, and therefore may represent a critical determinant of neurological injury. The in vivo marrow measurements will be examined for the degree of relationship to brain injury and neurocognitive impairment. The histological significance of these measurements will be evaluated with respect to levels of activated monocytes in the peripheral circulation and marrow biopsy findings of monocyte expansion and hypercellularity. Magnetic Resonance techniques for measuring the brain will be used to determine if injury occurs in early HIV infection. These techniques will also be used to determine whether specific factors are associated with changes in the brain in early and asymptomatic stages of HIV infection. Changes occurring in the bone marrow will also be studied as indicators of increased risk of brain injury in HIV patients.
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