Neurologic manifestations of AIDS.

An understanding of the biologic characteristics and cellular tropism of human immunodeficiency virus (HIV) is critical to appreciate the diverse neurologic manifestations of HIV infection in patients with the acquired immunodeficiency syndrome (AIDS). Only carefully designed prospective studies can provide information regarding prevalence, incidence, and natural history of the full spectrum of neurologic complications of HIV infection. A degree of tropism for monocyte/macrophages and possibly for cells within the CNS seems certain. One of the most frequent complications is AIDS-related dementia, which reflects central nervous system invasion by HIV. Despite the evidence linking unchecked viral replication within the brain and progressive dementia, the basic pathogenetic mechanisms remain obscure. Further characterization of the cellular targets of HIV within the brain, and the mechanisms which ultimately lead to the dementia, is critical. The demonstration that HIV enters the central nervous system during the earliest stages of infection has major implications for antiviral agents which must penetrate brain parenchyma to clear the virus effectively. Other neurologic complications occur frequently, including myelopathies, peripheral neuropathies, opportunistic CNS infections, and CNS neoplasms. Many of these disorders are novel and incompletely characterized and their etiology is uncertain. While treatment is available for several of these conditions, it is generally not curative, and is often poorly tolerated because of adverse effects. Research directions will focus on better understanding of pathogenetic mechanisms, on earlier and more precise detection of these diverse conditions, and on improved therapeutic agents. For the future, efforts toward the development of a safe, effective vaccine are of critical importance. There are, however, already up to 2 million individuals in the United States who are already infected with HIV and who are thus at risk for developing 1 or several of these neurologic complications. Vaccination, even if it were available now, is not likely to benefit these individuals. While it is hoped that only a fraction of this infected population will develop neurologic symptoms, the prospects of an epidemic of AIDS-related dementia are ominous, particularly as antiviral therapy alone is unlikely to either eradicate the virus or restore brain function. In Africa and worldwide the numbers at risk for HIV-related diseases are enormous, and the risk factors for transmission of HIV less well defined. There, economic and medical resources are less than adequate to deal with a problem of this magnitude.