New Therapy May Lead to AIDS Cure

A drug known for its anti-seizure and antidepressant activity is a key ingredient in a new combination therapy for AIDS that may direct the way to a cure for the disease, according to a study in the August 13, 2005, issue of The Lancet.

The study shows for the first time that the drug valproate (valproic acid) in combination with an intensified version of the standard AIDS drug cocktail known as HAART (highly active antiretroviral therapy) might eradicate dormant HIV viruses from their hiding place in resting immune cells. Prior research has shown that persistent infection in a reservoir of quiescent CD4+ T cells can prevent viral eradication by HAART.

"There are shortcomings to current antiretroviral therapy; currently it works 99.9% but that last 0.01% is still a problem. There remains low-level viral replication that goes on despite current therapy,” explained senior author Dr. David Margolis, professor of medicine, microbiology, and immunology in the School of Medicine at the University of North Carolina at Chapel Hill (USA; www.unc.edu).

Several years of research in the laboratory of Dr. Margolis led to the finding that a class of drugs developed to treat seizure and depression is targeting the HDAC1 (histone deacetylase 1) enzyme, which helps maintain HIV's latency. Valproate is one of those drugs. In a study designed to offer proof of concept, four adult volunteers infected with HIV and receiving HAART treatment also received injections of the drug enfuvirtide twice daily for six weeks. Oral doses of valproate twice daily were added to the regimen. Assays measured the latent infection of CD4+ T cells before and after the valproate treatment. The results showed a 75% average decline in latent infection, with a range from 68-84%.

"Dr. David Margolis' work is the first bright light at the end of a very long tunnel,” remarked Dr. Myron S. Cohen, professor of medicine at UNC. "Additionally, the findings, though not definitive, suggest that new approaches will allow the cure of HIV in the future.”




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