Neural Immunity and Human Immunodeficiency Virus-1-Associated Dementia

Human immunodeficiency virus (HIV)–1–associated dementia (HAD) is a metabolic encephalopathy caused by the viral infection of brain mononuclear phagocytes (MP) (perivascular and parenchymal brain macrophages and microglia) and sustained by paracrine–amplified, inflammatory responses. MP neurotoxins include, but are not limited to, proinflammatory cytokines, chemokines, platelet–activating factor, arachidonic acid and its metabolites, nitric oxide, quinolinic acid glutamate, progeny virions, and viral structural and regulatory proteins. These can damage neurons directly by engaging specific receptors or through inducing widespread inflammatory activities in brain tissue that ultimately affect neuronal injury and apoptosis. The mechanisms for immune and viral–mediated neural injury in HAD are made even more complex by the effects of abused drugs on cognitive function. Ultimately, linkages between neuronal function and disorders in MP immunity will provide insights into how HIV–1 infection of the brain leads to compromised mental function.