Pathogenesis of HIV asociated dementia

HIV-Associated Dementia is a progressive sub-cortical dementia that occurs in up to 20% of HIV/AIDS patients and is responsible for a significant amount of morbidity and mortality. Examination of brain tissue from HIV/AIDS patients has revealed:

1.      that there is no definitive correlation between the degree of neurological deficit and the extent of productive HIV infection
2.      that macrophages and microglia are the only cells productively infected with HIV
3.      that there is increased macrophage/microglial activation
4.      that the severity of disease correlates with the levels of TNFa, NO and quinolinic acid and inversely with the levels of IL4, suggesting a loss of macrophage regulation
5.      that HIV can non-productively infect astrocytes and
6.      that the mechanism of neuronal cell death in HIV-associated dementia is most likely to be apoptosis. 

Combining this information with findings from animal models and in vitro studies has resulted in the generation of a number of models for the neuropathogenesis of HIV-associated neurological disease. These models all have in common the central role of productively infected macrophages/microglia and the generation of neuronal cell death or dysfunction secondary to the production of neurotoxins by macrophages and/or astrocytes. These models suggest that therapeutic intervention should be aimed at control of intra-cerebral HIV replication and down-regulation of macrophage activation.

Associated Publication(s):
Thompson KA, McArthur JC, Wesselingh SL. Correlation between neurological progression and astrocyte apoptosis in HIV-associated dementia. Annals of Neurology 2001; 49(6): 745-752)