Drugs for Dementia, HIV Test Put to Test

November 1, 2006

The NIH’s National Institute of Mental Health is fundinga $60 million effort to find treatments to counteract HIV’seffects on the human brain.

The NIH's National Institute of Mental Health is fundinga $60 million effort to find treatments to counteract HIV'seffects on the human brain. In the early years of the epidemic,AIDS dementia caused degeneration in some personsto the level of degeneration in patients with endstageAlzheimer disease; death typically followed within6 months. With today's treatments, the often unpredictablecondition known as neuroAIDS is more subtleand appears 4 or more years before death. The memoryloss this condition generates can cause patients to forgettheir medications and further exacerbate their condition.Experts speculate that if HIV patients live long enough,virtually all will experience some neuroAIDS symptoms(Neergaard L. Associated Press. October 2, 2006).The NIH-backed research is taking 2 approaches. Thefirst is to determine which AIDS drugs give the best resultsfor patients with memory loss. Ron Ellis of the Universityof California, San Diego, said that while someAIDS drugs--such as nevirapine, abacavir, zidovudine,and indinavir--can cross the blood-brain barrier, it is notknown whether they can slow brain damage after theonset of neuroAIDS. Next year, Ellis will lead a study inwhich 120 patients will be assigned either to a brain-penetratingcombination or to other drugs.The second effort will seek to find drugs to protectnerve cells from inflammation-triggered toxicity. Twocandidate treatments are the epilepsy drug valproic acidand the manic-depression drug lithium. Both inhibit productionof the enzyme GSK-3b. Too much of this naturallyoccurring substance can be poisonous, and HIV damagesthe brain by causing an imbalance in the enzyme'sproduction. Astudy by Harris Gelbard, a neurologist atthe University of Rochester Medical Center, found indicationsthat valproic acid might increase brain connectionsin neuroAIDS patients.In addition, Gelbard hopes to launch human studiesof an experimental drug that targets a different inflammation-producing protein that HIV uses to make braincells self-destruct. [CDC HIV/STD/TB Prevention News Update,Friday, October 6, 2006]HIV Test: RNA Level Does Not Predict Rate of AIDS DevelopmentA new study by Case Western Reserve University AIDSresearchers has found that a low HIV RNA level does notpredict how rapidly AIDS will develop (Talan J. Newsday.September 28, 2006).Working with 4 other AIDS centers, Benigno Rodriguezand colleagues identified 2800 HIV-positive patientswho were not being treated because their RNA levelswere low. Each patient had at least 2 CD4+ cell countsavailable for study. The team found that the HIV RNAlevel did not predict whether CD4 immune system celllevels would fall (Rodriguez B, Sehi AK, Cheruvu VK, etal. JAMA. 2006;296:1523-1525)."Viral load is not helpful as a predictor of disease progression,"Rodriguez said. He noted that doctors shouldcounsel patients about starting treatment based on CD4+cell count, not HIV RNA level."Over time, we have realized that viral load doesn'ttell the whole story," said Pablo Tebas, an associate professorof medicine at the University of Pittsburgh. "Itgives us a different perspective and shows us how muchwe don't know about how this disease progresses."Tebas, who coauthored an editorial that accompaniedRodriguez's article, observed that this study suggests aneed for strategies based not just on the virus but on theimmune system and the person (Henry WK, Tebas P,Lane HC. JAMA. 2006;296:1523-1525). [CDC HIV/STD/TBPrevention News Update, Friday, September 29, 2006]

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