AIDS-dementia-complex: pathology, pathogenesis and future directions

Acquired immunodeficiency syndrome (AIDS), first described in 1981, is produced by infection with a retrovirus of the lentivirus family, now called human immunodeficiency virus (HIV). While, initially, the disease was almost exclusively seen in homosexual men, it has become apparent that numerous other categories of people are at risk, i.e., drug addicts who share dirty needles, hemophiliacs and haitians. In addition, epidemiological data from the industrialized nations clearly indicate that heterosexual contact is becoming an important source of viral transmission, as it has been known to occur in several african nations for many years. Initially, studies on patients with AIDS mainly focused on the immunosuppressive effects of the virus and on the various opportunistic infections and neoplastic complications that followed. Not much attention was given to a possible direct HIV infection of the nervous system. Consequently, patients who presented with neurological findings were simply considered to harbor in the CNS the same complications that occurred in other organs. While this was true in many cases, it has become also apparent that important changes in the central and peripheral nervous systems are due to direct viral involvement of these tissues. The first important step in the understanding of nervous system involvement in AIDS was the demonstration, in 1985, of HIV in the CSF and cerebral tissues of patients with neurological symptoms (47). Further studies have shown that, while opportunistic infections and neoplastic complications certainly contribute to the neurological morbidity of AIDS, the most important neuropathological changes, particularly in the brain, are due to direct HIV infection. The aim of this paper is to review the pathology of HIV-induced encephalitis and to discuss pathogenetic hypotheses regarding mechanisms of HIV-mediated tissue injury and the clinical manifestations that follow, particularly the syndrome now known as AIDS-Dementia-Complex (ADC). First, however, it may be appropriate to quickly review some basic notions on the biology of the virus.