Georgetown Research Uncovers New Mechanism For Suppressing HIV

The laboratory research, which was conducted by Michael Ruff, PhD, and Candace Pert, PhD, both research professors in the Department of Physiology and Biophysics at Georgetown University Medical Center, appears in the October issue of the journal Anti-Viral Research.

Peptide-T, which is a member of the newest class of experimental AIDS therapeutics known as “viral entry inhibitors,” works by adhering to a certain type of cellular receptor site (known as the chemokine R-5 receptor site), and preventing HIV from entering healthy cells. The compound, in effect, physically “blocks” the HIV and thereby prevents the cells from becoming infected.

This is a different mode of action than that employed by the most commonly used HIV therapy—protease inhibitors, which work by disrupting a key enzyme required for the viral assembly of HIV, so that it can no longer “fit” into cellular receptors.

One likely advantage of Peptide-T over protease inhibitors is that, whereas HIV develops an eventual resistance to the protease inhibitors -- and mutates in such a way that it is eventually able to enter the cells again -- this resistance has not been observed in cells treated with Peptide-T.

“If clinical trials produce the same results as our test tube studies, Peptide-T could one day be a treatment far better than protease inhibitors,” Ruff said. “While protease inhibitors have long been a method of treatment for a great many people, there are many drawbacks to this therapy including harmful side effects, great expense, a complicated regimen, and, most importantly, the ability of the virus to mutate and become resistant to the therapy.”

Another advantage of Peptide-T over protease inhibitors is that Peptide-T potentially could be given to patients at a much earlier stage than can protease inhibitors, if human trials bear out the laboratory results. Because HIV develops resistance to protease inhibitors over time, they are typically given only after virus levels rise to a certain level (usually 30,000 copies per milliliter of blood) and after the immune system has been significantly damaged.

This means that most patients do not begin HIV therapy until the disease is already fairly advanced, after many cells have been infected with the virus. But because HIV appears not to develop a resistance to Peptide-T-treated cells, it could potentially be given as soon as patients receive a positive diagnosis of HIV infection. And Peptide-T does not appear to cause many of the serious side effects experienced by people being treated with protease inhibitors.

Pert and Ruff’s experiments were repeated with similarly decisive results by three independent teams from the National Institutes of Health, the University of Pennsylvania and the University of Puerto Rico.

Their research was funded by Advanced Immunity Inc., a small, privately held New York-based company that licenses the worldwide exclusive rights to Peptide-T. The research was conducted at Georgetown and in the laboratory of Frank Ruscetti, PhD, of the National Cancer Institute, where the HIV strains are housed.

The Phase II clinical trial now under way in San Francisco involves 24 HIV-positive participants who will receive Peptide-T twice a day for six months. To qualify for the trial, patients must have T-cell counts greater than 300 and viral loads (a measurement of the amount of HIV in the blood) of less than 25,000 copies of the virus per milliliter of blood. The trial is currently recruiting participants. Patients who would like to learn more about the clinical trial may call Diane Cenko at 415-353-6215.