The Neuropathology of AIDS

AIDS (acquired immune deficiency syndrome) is a disease of an individual’s immune system caused by HIV-1 (human immunodeficiency virus 1). HIV-1 is a retrovirus of the lentivirus subfamily. This virus is atypical in that it does not require mitotically active cells to reproduce. Reproduction of the viral nucleic acids occurs in the nucleus of infected cells. Until recently it was believed that AIDS related deaths as a result of HIV infection were caused primarily by opportunistic infections, usually bacterial or fungal, gaining a foothold in an immuno-compromised individual. Many of these secondary infections are the result of T-cell mediated immunodeficiency induced by HIV. The sequels of HIV infection often leads to a neuropathological state as a result of unusual secondary infections such as Toxoplasmosis. Postmortem studies have demonstrated that in addition to secondary infection, neurological manifestations may be due to vascular events, tumors (CNS lymphoma) and direct HIV-1 infection. In humans, HIV is known to infect T-lymphocytes within the body binding to the CD-4 receptors present on the cell surface, but in the brain, recent studies have suggested that microglial cells and macrophages serve as the reservoirs of HIV. Direct central nervous system infection by HIV results in a condition known as AIDS Dementia Complex and as such will serve as the topic of this paper.

AIDS Dementia Complex is defined as a constellation of signs and symptoms characterized by cognitive and motor decline. HIV-1 infection occurs early in the course of the disease and may be the sole symptom of infection. HIV encephalopathy is the most common neurological disorder of HIV positive individuals, even more common than neurological opportunistic infections. HIV encephalopathy is characterized by slowly progressing cognitive impairment, psychomotoric slowing and increased apathy, and is limited exclusively to the late stages of HIV infection. It is estimated that between 40 to 70 percent of full-blown AIDS patients are affected by HIV encephalopathy. The mechanism by which HIV invades the brain and causes the subsequent encephalopathy are yet to be fully understood. It has been hypothesized that indirect effects of HIV infection of the brain are the most pathogenic factors. Certain viral proteins and cytokines produced by infected macrophages or activated microglia induce neuronal dysfunction and loss of nerve cells. An understanding of the role of microglia and its relationship with surrounding neuroglial cells appears to be vital.

Microglial cells are present at all levels of the neuroaxis including the spinal cord.