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New weapon may help flush stealth stashes of HIV in cells

29.09.2003


Researchers find positive results in people with HIV



The evolving science of "flushing" hidden reservoirs of HIV from cells got a encouraging boost today as researchers at Georgetown University Medical Center demonstrated how an experimental intranasal drug can activate the immune system and send HIV viral counts in white blood cells to undetectable levels.

Published in the latest issue of Peptides, this is the first human study to assess antiviral and immune effects of the experimental therapy, called Peptide T®. Although a small trial, it yielded statistically significant data on Peptide T’s ability to purify cells housing hidden HIV virus without any harmful side effects. This flushing mechanism gives promise to a new class of viral entry inhibitor drugs as a complement or perhaps even an alternative to the popular but costlier and complicated "highly active anti-retroviral therapies" (HAART) drug regimens.


"Every person in the study took Peptide T, and in each one of them, we observed quite a remarkable phenomenon – their white blood cell reservoirs of virus plummeted, some to undetectable levels," said Candace Pert, PhD, professor of physiology, co-discoverer of Peptide T, and lead Georgetown investigator of this study. "We’ve come a long way and undoubtedly have a ways to go, but the way Peptide T stirred the immune system and flushed the HIV cellular reservoirs is very encouraging to me."

Conceptually, Peptide T could play a valuable role in the fight against HIV. While current anti-retroviral drug cocktails successfully kill active, replicating HIV, the virus also has a frustrating ability to hide silently in cells for an indeterminate time period. A formidable foe, these hidden sources of virus may instantly be triggered and cause the virus to suddenly and aggressively kick start, beginning the chain of events that leads to the progression toward HIV/AIDS.

People with HIV currently remain on HAART drugs long after their virus plasma levels dip to undetectable levels simply because doctors know that hidden stores of virus hide within cells, looking for an opportunistic gateway to open and allow them to act up. If Peptide T one day conclusively flushes these hidden viral components out of the system for good, HIV-positive people could cease taking the costly drug cocktails they currently take as a defensive measure.

"Is flushing the viral reservoirs an actual clinical benefit? Can you actually get HIV-positive people off of HAART drugs as a result of taking Peptide T?," posed Michael Ruff, PhD, professor of physiology at Georgetown, co-discoverer of Peptide T and senior author of the study. "We simply do not know yet based on this data. However, there is enough evidence of clinical activity here to push Peptide T research to the next level to see if it really can serve as a valuable weapon against stealth stashes of virus."

Based out of St. Francis Hospital in San Francisco, 11 HIV-positive men were enrolled in the trial. All participants were classified as long-term non-progressors, meaning they had lived many years without their HIV developing into full blown AIDS. All participants also had low levels of viremia present in their systems upon entering the trial. Some had never been on HAART therapy, while others took HAART and Peptide T simultaneously during the 32 week-long trial.

At the conclusion, overall viral plasma levels had not changed, but all 11 men experienced profound reductions of HIV in the cellular reservoir.

Additionally, five out of 11 had a mean CD4 increase of 33 percent, a telltale sign of positive immune response in people with HIV, and each of these five responders showed an added immune response in the form of an increase in antiviral T cells that fight against HIV. The people who fared best took HAART and Peptide T simultaneously.

"There is a great deal of excitement about CCR5 entry inhibitors, and Peptide T may well be a novel one in the treatment of HIV," said Frank Ruscetti, prominent virologist and co-author of this study. "It is very clear that it served as an effective inhibitor of viral infections. I’d now like to see broader, placebo-controlled trials with a much more diverse patient base. Ideally we’d enroll people who have just been diagnosed with HIV, are HAART naïve, and some with much higher viral loads than those tested in this trial."

Drs. Pert and Ruff discovered Peptide T -- a synthetic compound of amino acids -- while Pert was serving as the chief of the brain biochemistry section at the National Institute of Mental Health in the late 1980s. It works by blocking HIV from entering cells by binding to the CCR5 receptors the virus uses to enter and infect cells. This is a much different action that antivirals that work directly on HIV or infected cells.

Earlier studies conducted on Peptide T sponsored by the National Institutes of Health have reported neurocognitive and brain imaging benefits of Peptide T in people with AIDS. Importantly, all previous studies have demonstrated that there are no toxicities associated with Peptide T.


The U.S Government holds the patent on Peptide T, as Dr. Pert discovered it while working for the NIH. Advanced Immunity, Inc. licensed Peptide T.

The Institute for New Medicine is a not-for-profit foundation founded by Drs. Pert and Ruff. Expert on Peptides, Inc. supports Drs. Pert and Ruff through support of their Georgetown salaries.

Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through our partnership with MedStar Health). Our mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis--or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing and Health Studies, both nationally ranked, and the world renowned Lombardi Cancer Center.

Lindsey Spindle | EurekAlert!
Further information:
http://gumc.georgetown.edu/

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