Important note: Information in this article was accurate in 2002. The state of the art may have changed since the publication date.
Newsday - February 26, 2002
Laurie Garrett, Staff Correspondent
The researchers cautioned that their work is preliminary, and none of the new drugs is likely to be available commercially for at least two years.
Still, the chemicals have generated considerable excitement among the 5,000 scientists and clinicians attending the Ninth Conference on Retroviruses here.
The first drug is a new approach to controlling HIV, by blocking the virus' ability to get inside human cells.
"This year I think will be remembered as the year of entry inhibitors," an ebullient Dr. Robert Schooley, of the University of Colorado Health Sciences Center in Denver, said in a news conference.
The drug, SCH C, "clearly in my view warrants development," Schooley said. It was developed by the Schering-Plough Research Institute in Kenilworth, N.J.
SCH C is a small molecule that attaches itself to bumps found on human immune system cells, called ccR5 receptors. HIV must lock onto these ccR5 receptors to gain entry into a cell. It cannot use ccR5 doorways if SCH C is locked onto the receptors.
In a preliminary eight-week study with 12 HIV patients who had been sick for many years, the SCH C drug proved reasonably effective used alone, without other AIDS drugs.
"There has been a clear antiviral effect," Schering Plough's Mark Laughlin said at the meeting. "This represents a clear proof of principle," that viral entry into cells can be blocked.
The SCH C chemical was invented by a Schering chemist, Stu McCombie and a virologist, Bahige Baroudy. They used computer 3-D models of the ccR5 receptor to come up with ideas of what sort of molecule might most effectively wrap itself around ccR5.
One downside of SCH C is its effect on the uptake of calcium by heart muscle tissue. Patients who took the highest, and most effective, doses experienced blips on their electrocardiogram heart monitors indicating potential heart complications. But taken in lower doses in combination with other anti-HIV drugs, the effect probably would not be dangerous, said Dr. Jeffrey Laurence of New York Weill Cornell Center.
One drug likely to find its way into the standard list of combination therapies is TNC-125, developed by the Belgian company Tibotec-Virco. It is not an entry inhibitor. Rather, TNC-125 targets the ability of HIV to make copies of itself.
What's different about TNC-125 is its potency, which independent researchers in Britain, Netherlands and Russia found remarkable.
For example, Dr. Brian Gauvard of Westminster Hospital in London tried the drug on 15 patients who were failing all other available anti-HIV therapies because of drug resistance. After only one week on TNC-125 all showed remarkable decline in the virus level, Gauvard said.
A Russian group tested TNC-125 on 12 HIV patients who had never taken any other anti-HIV drugs. After only five days the patients' viral loads dropped dramatically.
"This is very exciting," Dr. Joep Lange of the University of Amsterdam said in an interview. "Because it shows that we can develop agents that are an order of magnitude better than what we have now. It opens a whole new ballgame."
So far at this early stage, TNC-125 showed no side effects more severe than headaches, while the cocktail produces a vast array of side effects, some of them quite serious, such as partial paralysis and kidney disease.
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