Scientists Test Drugs for HIV Dementia

The National Institutes of Health's National Institute of Mental Health is funding a $60 million effort to find treatments to counteract HIV's effects on the human brain.

In the early years of the epidemic, AIDS dementia caused some with the disease to degenerate to the level of end-stage Alzheimer's patients; death typically followed within six months. With today's treatments, the often-unpredictable condition known as neuroAIDS is more subtle and appears four or more years before death. The memory loss it generates can cause patients to forget their medications, further exacerbating their condition. Experts speculate that if HIV patients live long enough, virtually all will experience some neuroAIDS symptoms.

The NIH-backed research is taking two approaches:

The first is to determine which AIDS drugs give the best results for patients with memory loss. Dr. Ron Ellis of the University of California-San Diego said that while some AIDS drugs -- such as nevirapine, abacavir, AZT and indinavir -- can cross the blood-brain barrier, it is not known whether they can slow brain damage after the onset of neuroAIDS. Next year, Ellis will lead a study in which 120 patients will be assigned to either a brain-penetrating cocktail or other drugs.

The second effort will seek to find drugs to protect nerve cells from inflammation-triggered toxicity. Two candidate treatments are the epilepsy drug valproic acid and the manic-depression drug lithium. Both inhibit production of the enzyme GSK-3b. Too much of this naturally occurring substance can be poisonous, and HIV damages the brain by causing an imbalance in the enzyme's production. In a study, Dr. Harris Gelbard, a neurologist at the University of Rochester Medical Center, saw indications that valproic acid might increase brain connections in neuroAIDS patients. A second-stage study will determine if the effect is real; a similar trial with lithium is under way.

Gelbard further hopes to launch human studies of an experimental drug targeting a different inflammation-producing protein HIV uses to make brain cells self-destruct.

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