Mechanisms of HIV infection of the central nervous system and pathogenesis of AIDS-dementia complex

In many patients with AIDS, severe neurologic deficits develop that have been designated the HIV-associated cognitive-motor complex. Pathologically, these symptoms correlate with a low-grade inflammatory condition, referred to as HIV encephalitis, in which the most characteristic change is the presence of multinucleated giant cells. Cortical changes include neuronal loss and alterations of dendrites and synapses. There is pallor of white matter generally associated with the mononuclear inflammatory infiltrates. The only cells that seem to be directly infected by HIV are the microglia/monocyte and the giant cells derived from fusion of monocytes. It is hypothesized, therefore, that cortical and white matter alterations in patients with this syndrome depend on the production of injurious soluble factors liberated by these cells and by astrocytes under the influence of many of these same factors. This article reviews recent advances in the understanding of these secondary effects and discusses pathogenetic mechanisms of tissue injury.