Neurocognitive complications are estimated to occur in 30-50 percent of all individuals infected with HIV and these behavioral pathologies can significantly impact quality of life. While early data suggest that highly active antiretroviral drug therapy (HAART) may have beneficial effects on cognitive dysfunction, the unknown duration of these actions and the fact that most HIV+ patients worldwide are not maintained on HAART emphasize the need for further study of the behavioral sequelae of HIV disease. A neuropsychological test battery employing a touch-sensitive computer screen has been developed to detect changes in cognitive performance of rhesus monkeys. The battery includes probes of memory, learning, attention, motor performance and reaction-time as well as an estimate of relative reinforcer efficacy. In monkeys, a neurovirulent form of simian immunodeficiency virus (SIV) produces a specific profile of deficits in this behavioral battery entirely consistent with those seen in humans with HIV disease. Performance in motor tasks, reinforcer efficacy and spatial working memory tasks are the most commonly disrupted. Evidence suggests that higher sustained viral loads are associated with rapid disease progression and an increase in the incidence and severity of neurobehavioral symptoms. This proposal will study the relationship between viral burden and behavior by employing experimental manipulations which result in the elevation or lowering of viral load during critical phases of infection. The concomitant measurement of body temperature and spontaneous locomotor activity with radiotelemetry, as well as recording of sensory evoked potentials will provide important adjuncts for charting the functional effects of disease progression.
The Specific Aims are I) To investigate the effects of reducing CD8+ T cell populations with the CD8 specific antibody cM-T807 early in the course of infection on the incidence and severity of behavioral pathology; and II) To investigate the effect of rapid reduction of viral load with anti-retroviral combination-therapy on CNS functional outcome. Because we have shown that monkeys infected with SIV demonstrate behavioral deficits analogous to those observed in HIV infected humans, the use of this behavioral battery to study the role of viral burden is a valuable and productive approach towards a further understanding of NeuroAIDS.
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