Neuropathogenesis of acquired immunodeficiency syndrome dementia.

During the past year progress has been made in our understanding of the pathogenesis of the dementia associated with the acquired immunodeficiency syndrome. As many as one-third of acquired immunodeficiency syndrome patients eventually develop this condition, and at present it remains only poorly or transiently treated by existing antiretroviral therapies which do not penetrate well into the central nervous system. The past year has witnessed further characterization of microglial/macrophage neurotoxins, increasing evidence for neuronal death by apoptosis, and a more quantitative search for viral products, surrogate markers, or magnetic resonance spectroscopic parameters of brain or cerebrospinal fluid, or both. An increased understanding that the mediation of neuronal injury is not by direct infection of neurons, but rather via a complex network of cytokines, excitotoxins, and free radical mechanisms triggered by human immunodeficiency virus-infected or immune-stimulated brain macrophages and astrocytes has led to the development of therapies that are administered adjunctively with antiretroviral drugs. Some of these potential new treatments have now entered clinical trials.