Associated Press - Monday, November 02, 1998

In preliminary research published in the November issue of the journal Nature Medicine, a team at the University of Alabama at Birmingham treated patients with a new drug, called T-20, that fights HIV-1 differently from the compounds that make up the potent cocktails now saving lives.

The doctors treated 16 patients, in groups of four, with varying doses of T-20 for two weeks. The amount of virus in the blood dropped to undetectable levels in four patients getting the highest doses of T-20, which was injected twice a day, says Michael Saag, a professor of medicine and an author of the study.

The anti-viral activity, the scientists say, was unequivocal and of substantial magnitude. Saag says they saw a 100-fold drop in virus during the study, a drop he describes as comparable to that achieved by hottest new anti-AIDS drugs -- the protease inhibitors.

Scientists believe that T-20 -- a synthetic peptide or protein fragment -- probably will be used first in patients who have developed resistance to current therapies, or in those who are not helped at all by today's drugs.

Saag says, "This is the proof of a concept of a third major avenue of attack."

The study was sponsored by the drug maker, Trimeris Inc., a biotechnology company in Research Triangle Park, N.C.

Currently available AIDS drug, such as AZT, 3TC and the protease inhibitors, are aimed at enzymes that allow HIV-1, the virus that causes the deadly disease, to grow in a patient's body.

The new drug fights AIDS in a different way, by preventing a process called fusion, in which the virus tucks itself into the cell. Chemist M. Ross Johnson says, "The fusion mechanism is the central thing, the fatal handshake.

Johnson, who heads Trimeris and was one of the authors of the paper, says that currently available anti-AIDS drugs work after infection, while T-20 prevents infection.

The AIDS virus uses a molecule called gp41 to perform the fusion process. T-20 jams this molecule, leaving the virus floating around aimlessly until it dies, says Saag.

The current trial is the first to show that this method can work in living AIDS patients.

Saag says, "This is the third principal mechanism of fighting HIV. It's totally new; that's what's exciting about it."

No side effects were seen during the study, although Saag admits that patients received the drug for only 10 to 14 days, which may have been too short a time for side effects to appear.

Saag says, "This gives us another fairly potent agent."

One drawback to the drug, Saag says, is that it cannot be packed in a pill, because stomach acids would render it useless. So patients would have to give themselves under-the-skin injections of T-20. For that reason, he says, it is unlikely to be a first-line drug.

But he says the study shows for the first time that interfering with the gp41 molecule can lock out the virus. That means scientists may be able to cook up compounds that work in the same way but overcome these problems, or that may be even more potent.

Johnson says Trimeris is currently conducting a 78-patient trial in investigating two routes of administration -- under-the-skin injections and a pump, similar to the one used by diabetics to take insulin.

If all goes well, the company expects to ask for marketing approval for T-20 in about two to two-and-a-half years.

He says the company is looking for other compounds that work the same way, but may be taken in pill form.

In a commentary on the study, Dr. Douglas D. Richman of the University of California San Diego says the work provides proof-of- concept, and certainly any new drug that shows promise against HIV is very welcome.

But he says more research is needed to show that T-20 will be an effective therapy, particularly long-term studies that examine side effects and the potential for the development of strains of the virus that are resistant to the new drug.

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