Rate and severity of HIV-associated dementia (HAD): Correlations with Gp41and iNOS

Background: Fifteen to thirty percent of AIDS patients develop some type of neurologic disorder during the course of their illness and the vast majori ty of these neurologic disorders will be HIV-associated dementia (HAD). The se patients can exhibit varying degrees of severity and rates of progressio n of HAD. Neuropathologic variables that are associated with the rate of pr ogression of HAD are not known. Materials and Methods: Tissue was collected at autopsy from the Johns Hopki ns University HIV Neurology Program. Seventy-one AIDS patients of this pros pectively characterized population were followed until death to obtain info rmation on dementia severity and the rate of neurological progression. Immu noblot analysis of immunological nitric oxide synthase (iNOS), HAM56, gp41, p24, gp120, and beta-tubulin was performed and the levels of iNOS, HAM56, gp41, and p24 were normalized to beta-tubulin and analyzed for significance by means of the Kruskal-Wallis test for multiple groups. Results: We have identified unique groups within this spectrum and designat ed them slow, moderate, and rapid progressors. Slow and moderate progressor s' neurological progression occurs over a course of months to years, wherea s the rapid progressors' disease shows rapid increases in severity over wee ks to months. In the present study we demonstrate that the severity and rat e of progression of HAD correlates significantly with levels of the HIV-1 c oat protein, gp41, iNOS, and HAM56, a marker of microglial/macrophage activ ation. Conclusion: The severity and rate of progression of HAD correlates with ind ices of immune activation as well as levels of iNOS and gp41. There appears to be a threshold effect in which high levels of gp41, iNOS, and immune ac tivation are particularly associated with severe (Memorial Sloan-Kettering score 3 to 4) and rapidly progressive HAD.