AIDS dementia complex (ADC) is one of the most frequent and serious neurologic complications of HIV. It is characterized by cognitive dysfunction (trouble with concentration, memory and attention), declining motor performance (strength, dexterity, coordination) and behavioral changes. It occurs primarily in more advanced HIV infection when the CD4 cell counts are relatively low. While the progression of dysfunction is variable, it is regarded as a serious complication historically predicting death in less than one year. Diagnosis is made by neurologists who carefully rule out alternative diagnoses. This routinely requires a careful neurological examination, brain scan (MR or CT) and a lumbar puncture to evaluate the cerebrospinal fluid. No single test is available to confirm the diagnosis, but the constellation of history, laboratory findings, and examination reliably establish the diagnosis when performed by experienced clinicians.

The cause of ADC is not fully known at present. Presence of the HIV virus is required, and there is good evidence that successful antiretroviral therapy, if started early enough, can induce a degree of improvement in neurologic performance. Evidence that antiviral therapy prevents ADC is incomplete and in some cases contradictory. However, most investigators recommend at a minimum that aggressive antiretroviral therapy with maximally CNS penetrating drugs be used when this diagnosis is likely. Since the amount of virus in the brain does not correlate well with the degree of dementia, most investigators believe that secondary mechanisms are also important in the manifestation of ADC. Current hypotheses with variable levels of scientific support include contributions by cytokines such as tumor necrosis factor, toxic portions of the viral molecule (such as gp120 from the viral envelope), excitatory amino acid mediated mechanisms, and calcium mediated neurotoxicity as playing some role in this disorder.

Current experimental studies available at some centers include:

ACTG 301 tests a neuroprotective substance, memantine, in a controlled trial adding this potentially neuroprotective drug to best anti-retroviral therapy. This important trial seeks to test the role of neurotoxic mechanisms while patients continue to get maximal antiretroviral therapy. This drug may also play a beneficial role for peripheral neuropathy in HIV, and patients with both cognitive-motor deficits and neuropathy may participate. All patients will have access to memantine at the conclusion of the controlled portion of the trial. The Principal Investigator is Dr. Brad Navia. NARC 003 is a trial in development that will test CPI-1189, an agent that has an tumor necrosis alpha antagonist property. Anticipated start date for this trial will be September 15, 1998. Anticipated sites: Washington University (St. Louis), Columbia University (New York), Johns Hopkins University (Baltimore), University of Rochester (NY), Northwestern University (Chicago) and University of San Diego (CA).

In all cases, it remains important to seek a maximally effective HIV treatment regimen when dementia develops. Efforts to bring viral load to the lowest possible level in serum (and probably in CSF) should be primary goal for all treating physicians. Antivirals with good CNS penetration including zidovudine, D4T, nevirapine, and abacavir may be used preferentially if they have not already failed.

These trials are important because they extend the range of therapies available, and also because they are serious efforts to correlate the clinical manifestations of ADC with prospectively collected samples of serum and csf in patients with dementia to further study the pathophysiology of this disorder. With more certain understanding of the pathophysiology, more appropriate and specific therapies can be designed for the future. Additional studies to evaluate brain metabolism in this disorder by such means as positron emission tomography or magnetic resonance spectroscopy are available at selected centers. Other centers are actively attempting to evaluate the role of viral loads in the cerebrospinal fluid as it relates to the development of dementia, and to follow this parameter over the course of treatment.

Next

Back to the AIDS Dementia Index

Home