IMMUNOCYTOCHEMICAL QUANTITATION OF HUMAN-IMMUNODEFICIENCY-VIRUS IN THE BRAIN - CORRELATIONS WITH DEMENTIA

The pathogenesis of human immunodeficiency virus (HIV)-associated deme ntia is unclear, and the underlying pathological substrate has been a matter of debate. In a prospectively clinically characterized populati on of acquired immunodeficiency syndrome (AIDS) patients we investigat ed the relationship between the clinical syndrome of HIV-associated de mentia and the presence and relative quantity of immunocytochemical ma rkers for HIV-1 (gp41 antibody), and for macrophages and microglia (HA M-56 antibody). Sections from the basal ganglia and frontal lobes from the brains of 51 patients were studied, and the data were stratified for severity of dementia (16 nondemented, 12 mildly demented, 23 sever ely demented), rate of dementia progression, duration of AIDS, use of antiretrovirals, and several other demographic features. We found a hi ghly significant correlation between the degree of macrophage staining and the severity of dementia but only a borderline correlation betwee n the presence and amount of gp41-positive cells and dementia. Several nondemented patients showed abundant gp41 immunoreactivity, and some severely demented showed little to no gp41 immunoreactivity. Other cor relations with the immunostaining data, including antiretroviral use, were not significant. We conclude that the presence of macrophages and microglia is a better correlate with HIV-associated dementia than is the presence and amount of HIV-infected cells in the:brain. These data support the concept that the pathogenesis of HIV-associated dementia is likely due to indirect effects of HIV infection of the brain, possi bly through the actions of macrophages and microglia.