Anti Viral Drug Shows Promise In Treatment For HIV - Without Drug Resistance

Bavituximab, an anti-viral drug developed by researchers at UT Southwestern Medical Center, is showing promise as a new strategy to fight viral diseases, including HIV.

In a study published in the December issue of Nature Medicine, groups of guinea pigs infected with a virus similar to Lassa fever virus recovered from the fatal disease when treated with bavituximab in combination with a common anti-viral medication. Bavituximab treatment also cured mice infected with cytomegalovirus, an opportunistic infection that afflicts AIDS patients.

Dr. Philip Thorpe, professor of pharmacology at UT Southwestern and senior author of the study, proposed that phosphatidylserine, a lipid molecule that is normally positioned on the internal surface of a cell, flips to the outside of the cell when the cell is infected by a virus. His laboratory developed bavituximab, which binds to phosphatidylserine on the infected cells. Dr. Thorpe predicted that this interaction would muster the body's immune cells to attack and destroy the infected cells before the virus has a chance to replicate.

"When injected into the bloodstream, bavituximab circulates in the body until it finds these inside-out lipids and then binds to them," said Dr. Thorpe. "In the case of virus infection, the binding raises a red flag to the body's immune system, forcing the deployment of defensive white blood cells to attack the infected cells."

In an experiment, researchers administered both bavituximab and the anti-viral medication ribavirin. Ribavirin works by a different mechanism than bavituximab; it stops virus replication in the cell. With this combination therapy, 63 percent of guinea pigs survived.This is the first report of a therapeutic treatment being effective against advanced Lassa-like fever infections in animals.

Dr. Melina Soares, instructor of pharmacology at UT Southwestern and lead author of the Nature Medicine study, said, "As viruses mutate, they become more resistant to existing anti-viral drug therapies. Using bavituximab to attack a lipid target could prove to be a new and effective strategy for treating virus infections."

"This approach reduces the ability of the virus to escape attack by a drug," he said. "Viruses often dodge drugs by mutating into a different form that the drug is ineffective against. Host cells are a more immutable target." making drug reistance less problematic, according to Dr. Thorpe.

Researchers have found that phosphatidylserine flipping occurs in cells infected with a host of viruses including HIV. The drug "could lead to a new, broad spectrum anti-viral treatment." Dr. Soares said.

Peregrine Pharmaceuticals has exclusively licensed bavituximab from UT Southwestern and has a sponsored research agreement to develop the drug further. Dr. Thorpe is a consultant to and has an equity interest in the company.

The research was funded by the National Institutes of Health and Peregrine. Press release provide by Peregrine Pharmaceuticals. Peregrine is a small pharmaceuticals company based in Tustin, CA.