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Inflammatory processes implicated in HIV-related dementia

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WESTPORT, CT (Reuters Health) – In HIV-infected patients, controlling viral levels in the brain may not be sufficient to prevent HIV-related dementia, according to findings published in the October 23rd issue of Neurology. In fact, brain tissue inflammation appears to be the primary cause of dementia, study director, Dr. Justin C. McArthur told Reuters Health.

Dr. McArthur, a researcher at Johns Hopkins Hospital, in Baltimore, and colleagues examined the association between HIV RNA levels in brain and peripheral tissues, antiretroviral resistance mutations and neurologic status in autopsy specimens from 13 HIV-infected patients. Of the patients, seven were characterized antemortem as nondemented, three as mildly demented and three as moderately/severely demented.

The median HIV-1 RNA load in brain tissues increased significantly from nondemented patients to mildly demented patients to moderately/severely demented patients, the investigators found. However, "some demented subjects had relatively low levels of HIV-1 vRNA, and paradoxically some nondemented subjects had high vRNA brain levels."

On the other hand, Dr. McArthur told Reuters Health, "there was a closer relationship between the level of neurological impairment and the degree of inflammation than with the level of HIV."

In other words, it appears that HIV dementia may be only an indirect effect of HIV, he said, and that "simply lowering the amount of HIV in the brain may not be sufficient to correct this." The findings implicate other events associated with brain tissue inflammation, such as macrophage activation, in the pathology of HIV dementia, Dr. McArthur continued.

This has pointed him and his colleagues in new directions for treating HIV dementia. Preliminary studies suggest that the antiparkinsonian agent selegiline, which blocks the inflammatory response in the brain, can have a "very positive effect on neurologic deficits in patients with HIV dementia," Dr. McArthur indicated. A larger trial of this drug is currently under way.

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