HIV NEUROPATHY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. With recent declines in the incidence rates of HIV-associated dementia, HIV-associated sensory neuropathy (HIV-SN) is the commonest of the neurological disorders associated with AIDS. It affects up to 30% of patients and is associated with advanced HIV disease, and with dideoxymicleoside agents. To date research efforts have focused on adult patients, and it is unclear whether children are vulnerable to this complication. The pathophysiological mechanisms, which underlie HIV-SN remain undefined. Our underlying hypothesis is that symptomatic neuropathy in AIDS develops through the magnification of pre-existing nerve damage. HIV-induced immune dysregulation with local macrophage activation plays a critical role. We propose a prospective and longitudinal study of peripheral neuropathy in a Hispanic cohort of pediatric and adult HIV-Infected patients to address these questions. The rationale for the proposed study centers on the fact that there is very limited information about determinants of neuropathy in specific age or ethnic groups and this information should pen-nit the implementation of specific and effective therapeutic or preventive strategies. To accomplish the objectives of this application we plan to pursue the following specific aims: 1) To compare the incidence rates and determinants of sensory neuropathy in cohorts of HIV seropositive children and adults. 2) To determine the association between nucleoside analogue metabolism and peripheral neuropathy by measuring intracellular concentrations of phosphorylated nucleoside analogues in PBMCs. 3) To determine the relationship between macrophage dysregulation, immune activation and the development of sensory neuropathy. 4) To determinate how the patterns of immune activation and peripheral nerve damage in HIV sensory neuropathy affect the remodeling of the dorsal horn of the spinal cord and molecular pathways associated with pain in the dorsal root ganglia.