and a descriptive staging system, useful to provide a common vocabulary for both clinical practice and clinical investigation, has been developed (see Price, 1994; Sidtis, 1994). However, the character of HIV infection of the CNS is not yet fully understood. Changes in the virus, with respect to both predominant cell tropism and virulence may be important. A number of studies have shown early invasion of the CNS and early local host immune responses in the cerebrospinal fluid (CSF). A critical question remaining to be answered is whether the virus then persists in the CNS in latent form or as an indolent infection that is asymptomatic. If it can remain latent, it is important to know what cells might harbor the proviral DNA: microglia, astrocytes, or other CNS cells. Pathological observations to date suggest that the virus indirectly injures the brain rather than directly killing or infecting nerve cells. This distinguishes HIV from other viral infections of the brain, such as those caused by poliovirus or herpes simplex virus.

Understanding the pathogenic mechanisms has great potential importance for treating ADC patients not only using methods that interfere with the virus, but also strategies directed at interrupting some of its toxic processes. Indeed, these considerations underlie some of the approaches now being taken to treat ADC, including treatment protocols using nimodipine, a calcium channel blocker that can prevent gp 120-induced neuronal death in vitro, and pentoxyphilline, an antagonist of Tumor Necrosis Factor.

Research on ADC and CNS HIV infection has biological importance not only for understanding the nature and course of HIV infection, but also more generally for suggesting mechanisms involved in other infectious, immunological, and neurodegenerative diseases. The early penetration of the blood-brain barrier by HIV, the local immune response detected in the spinal fluid, and the subsequent active replication of HIV in the brain late in infection hold clues regarding the CNS ecology of HIV.

INTERACTIONS AMONG HIV, SUBSTANCE USE, AND MENTAL ILLNESS

The second type of interaction among brain, behavior, and HIV relates to the unique issues associated with multiple diagnoses, that is diagnosis of any combination of HIV, drug or alcohol abuse, and mental illness.

Drinking alcohol to excess has been shown to cause damage to the immune system (Kruger and Jerrells, 1992). It therefore seems reasonable to assume that alcohol consumption in significant amounts



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