A new "cocktail" of three antiviral drugs can force the lethal AIDS virus into hiding, at least temporarily, according to new research.

The findings cap a 10-year search for a medicine to disable a key enzyme in the AIDS virus. When first identified in 1986, the enzyme, called protease (pronounced PRO-tee-ace), triggered a worldwide race that at times involved more than a dozen drug makers.

At a week-long conference in Washington, D.C., that started yesterday, Abbott Laboratories and Merck & Co. will show that each of their protease-blocking drugs, when combined with two existing AIDS medicines, packs an unprecedented antiviral wallop.

If early test results hold up as researchers expect, the three-drug regimen will be the first major advance in AIDS therapy since AZT was introduced in 1987. The first protease-blocking drug was approved by the FDA in December, and two more may gain marketing go-ahead in the next few months. Two others could be released for general use next year.

In preliminary tests, the triple-drug cocktail eliminated 99% of the AIDS virus detectable in the bloodstream of almost all of 45 patients tested for between four and six months. And one combination study involving Abbott's drug, Norvir, produced one of the most remarkable results yet: In six of 21 AIDS patients, the virus was impossible to detect, suggesting to researchers that they may have eliminated the virus from the patients' blood altogether.

"We're not saying we have a cure," says John Leonard, Abbott's protease project director. "But [the new results] show we are making very significant strides in that direction."

Few scientists truly expect the three-drug therapy to rid the body of HIV, the deadly AIDS virus. Past experience has shown that the virus may be lurking somewhere in the body and is likely to develop resistance to the drug cocktail eventually, perhaps re-emerging as dangerous as before. The drugs will likely produce side effects making them unusable for some patients, and the three-drug therapy costs more than $12,000 a year.

But the new results are exciting because the combination of drugs is so effective against HIV that researchers can't detect the presence of the virus in many patients' blood even when they use the most powerful detection techniques available.

"It's a very extraordinary result," says Anthony Fauci, who directs the National Institute of Allergies and Infectious Diseases. "There are some important questions to be answered over the next few months about how valuable [viral suppression] is for a patient's well-being. But what we're hearing is impressive."

Excitement about the protease inhibitors has been rising since early last year, when Merck, Abbott and Hoffmann-La Roche Inc. publicly presented results that demonstrated the drugs' significant antiviral potency in patients. Since then, all three companies have aggressively stepped up patient testing and, under a special program sanctioned by the Food and Drug Administration, offered drugs free to several thousand seriously ill AIDS patients in the U.S. and abroad.

The FDA approved the first protease blocker, Roche's Invirase, for use when combined with at least one of two already-used drugs, such as Glaxo Wellcome PLC's AZT.

In one of the new studies to be released later this week, Merck tested its protease-blocking drug, Crixivan, in combination with AZT and another Glaxo Wellcome drug, 3TC. After four months, 24 of the 26 patients taking the three drugs had virus levels so low they couldn't be detected. The same was true of 13 of 26 patients taking Crixivan alone. Patients taking AZT and 3TC had "their virus lowered, but the virus remained detectable," says Emilio Emini, Merck's director of antiviral research.

In addition, patients taking the three drugs had an apparent increase in their bodies' infection-fighting "CD4" cells, which are destroyed over time by the AIDS virus. Healthy patients have CD4 "counts" of about 1,000; many AIDS patients tested had counts below 100. The triple-drug regimen produced a median increase in CD4 counts of 146, Crixivan alone resulted in a median increase of 96, and a combination of AZT and 3TC brought a median increase of 22, Merck says.

"Leaders in AIDS research have theorized that by adding a very potent protease inhibitor like Merck's Crixivan to other [antiviral AIDS] drugs, one could knock down the virus to undetectable levels and significantly reduce the [virus's] ability to reproduce," says Dr. Emini.

"While these results are early," he adds, "they are the strongest evidence to date that this approach may work."

Dr. Emini described Merck's findings briefly in an overview speech yesterday at the Third Conference on Retroviruses and Opportunistic Infections. A full presentation of Merck's results will be presented Thursday. Abbott's 21-patient study, done in France, will be formally presented today.

Tomorrow, Abbott will present the results of still another test, which, for the first time, will describe whether patients' health significantly improved as a result of taking the triple-drug regimen. Abbott officials declined to divulge those results early.

AIDS researchers and doctors say that if the findings do remain positive, the new drugs may be used by as many as 100,000 patients in the U.S. If true, Merck and Abbott each could generate sales of several hundred million dollars each -- or more.

At present, Roche is charging about $6,000 at wholesale for a year's supply of its drug, and some people close to Merck and Abbott predict their drugs will cost about the same, possibly making the therapy inaccessible to many patients.

Researchers who have heard about the drug companies' test results are being cautious, arguing that the new therapy must be tried in many more patients over many more months before its true importance will be known. "We now must find out how long the striking effect being seen lasts," says the government's Dr. Fauci. "It's my guess that even in patients where the virus is undetectable that some virus is hiding in the body. But we now need to find that out."

--- Protease Drugs

DRUG COMPANY STATUS

Invirase (saquinavir) Hoffmann-La Roche Available

Norvir (ritonavir) Abbott Filed FDA application

Crixivan (indinavir) Merck Filing FDA application this week

Viracept (nelfinavir) Agouron Human testing

VX478 Glaxo-Wellcome Human testing and Vertex Pharmaceuticals