HIV in the CNS


Etiology:

HIV infection is responsible for central nervous system (CNS) complications that include: opportunistic infections of the CNS, tumors, HIV encephalopathy (HIVE), HIV associated dementia (HAD), AIDS Dementia Complex (ADC) and Minor Cognitive Motor Disorder (MCMD) now known as mild cognitive disorder (MCD), etc.

Evidence of HIV has been demonstrated in the CNS within 15 days following initial viremia. It is believed to be transported across the blood brain barrier by infected peripheral macrophages. When an infected macrophages enters the CNS, it disperses HIV, infecting microglia, astrocytes, other macrophages and neurons. Unfortunately the blood brain barrier limits the passage of many antiretroviral medications into the CNS. This results in a sequestered source of HIV that can be covertly replicating even when serum HIV is undetectable.

Neuropathology:

HIV is known to infect a number of CNS cell types:

HIV related CNS pathology appears to concentrate within the deep gray matter and central white matter of the brain. Imaging studies indicate that these changes are progressive and may be due to cell death and/or demyelination. A correlation between deteriorating cognitive function and reduced brain volume in the basal ganglia has been demonstrated.

A number of in vitro and animal studies have described HIV neurotoxic mechanisms. These studies have identified specific HIV proteins and cellular immune responses as principle factors.

Epidemiology:

A 2002 autopsy review of consecutive HIV positive decedents between 1984 and 2000 revealed that HAART (highly active antiretroviral therapy) significantly reduces the number of HIV related CNS lesions. The following four time periods were matched to treatment and the % with CNS lesions: 1984-1987 (no treatment)-54%, 1988-1994 (AZT only)-32%, 1995-1996 (dual NRTI therapy)-18%, 1997-2000 (triple therapy 2 NRTIs and protease inhibitor)-15%.

Research: Current antiretroviral treatments are only able to slow the progressive CNS damage associated with HIV infection. Recent studies indicate that good CNS penetration effectiveness (CPE) by antiretroviral drugs was associated with lower CSF viral RNA concentration.


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