A naturally occurring protein may provide a safe harbor to the virus that causes AIDS by acting as a barrier to prevent the newest medications from reaching the virus, Vanderbilt University Medical Center researchers have found.
The finding raises hope that the effectiveness of protease inhibitors could be boosted by combining the anti-HIV drugs with medication to block the action of the protein protecting the virus.
That strategy might also reduce the cost of the now-very-expensive therapy by reducing the dose needed to get enough of the drugs into the bloodstream, where it can attack HIV.
"Protease inhibitors work very well and have resulted in many patients becoming healthier," said Dr. Richard B. Kim, assistant professor of Medicine and Pharmacology.
"However, there are limitations. Not all patients do so well on the drugs. And even in those patients for whom anti-HIV therapy is very effective -- whose blood levels of HIV drop to undetectable levels using very sensitive techniques -- studies have shown that when they stop taking the drugs, the virus comes back. That means there must be sanctuaries where the virus can live and hide out."
Kim and his colleagues in the division of Clinical Pharmacology have found evidence that a "transporter molecule" called P-glyco protein (Pgp) may be creating these hide-outs. Transporter molecules protect the body from poisoning by recognizing groups of chemicals and pumping them out of cells as soon as they enter.
Their research is the subject of an article and accompanying editorial in the January 15 issue of the Journal of Clinical Investigation, published by the American Society for Clinical Investigation.
In cell cultures that express large quantities of Pgp, the VUMC researchers found that protease inhibitors were not readily absorbed by the cells.