Withstanding the artillery of brainpower, billions of dollars and 17 years worth of medicines dedicated to its defeat, HIV has been a moving target for the last two decades.

It evades eradication by mutating into different forms, confusing entire classes of HIV drugs and rendering them useless, resuming its rapid reproduction of itself.

But an international team of researchers believes it has discovered a drug so flexible that it can, as the scientists put it, “wiggle” and “jiggle” with HIV as the virus tries to mutate, mimicking the mutation so that the drug will continue to block the disease from copying itself.

The drug, R278474 — one of a new family of non-nucleoside reverse transcriptase inhibitors known as DAPYs — would ideally be taken orally once daily, adding to the optimism that it could represent a new generation of weapons to fight the disease that has killed more than 23 million people across the globe.

“The conclusions we have drawn do not represent an endpoint, but rather punctuation marks — places where we have achieved some significant milestones that will help guide us in the design of new and more effective anti-AIDS drugs,” said Eddy Arnold, a researcher at Rutgers University who was involved in developing the new DAPY.

Arnold and 25 other AIDS researchers pre-published their findings in the online version of the Journal of Medicinal Chemistry. The full findings are expected to be published in early 2005.

The drug R278474 is the latest prototype of reverse transcriptase inhibitors, medicines that interfere with reverse transcriptase, a key enzyme in HIV’s ability to reproduce itself. If RT fails to function, the virus cannot duplicate itself in healthy cells and will die.

Animal tests conducted by Arnold’s team, along with Janssen Pharmaceuticals and Tibotec-Virco, both subsidiaries of Johnson & Johnson, reveal that R278474 is easily and safely absorbed, according to the Journal of Medicinal Chemistry report.

The discovery of new HIV drugs has always been accompanied by optimism, but patients and doctors have been repeatedly dispirited by a mutating virus and drugs with unbearable side effects.

The cunning persistence of HIV keeps Philippe Chiliade, medical director at the Whitman Walker Clinic in Washington, D.C., from getting overly optimistic when promising drugs are on the horizon.

“The problem we have faced is that we’ve seen when the virus develops a resistance to one drug of a class, it develops a resistance to other drugs within that same class,” Chiliade said.

There are currently about 20 HIV-fighting drugs on the market, broken into four major classes: nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors and fusion inhibitors.

When the first HIV drug — AZT, a NRTI — was released in 1987, doctors knew little about what the proper dosage should be, Chiliade said.

The drug prevented reverse transcriptase from copying and spreading HIV to healthy T-cells, but people with the disease had to take high doses frequently with rigid restrictions and face serious side effects, Chiliade said.

Prior to 1991, HIV medicines were taken individually, but as more drugs developed researchers learned that certain ones worked well in combination with others and staved off HIV mutating, Chiliade said.

In the mid-1990s, protease inhibitors — which block protease, an enzyme that helps HIV cells produce new copies — were introduced and added to the growing group of drugs that could be used in AIDS “cocktails.”

If R278474 turns out to be resistance-proof, it will be a major breakthrough in containing HIV. But its developers remain cautiously optimistic.

“Given we don’t have any of this data in patients at this time, it’s difficult to say [what the drug’s potential is],” said Karen Manson, a spokesperson for Tibotec.

The drug is in the early stages of FDA approval, completing Phase I and Phase II human testing to gauge its safety and efficacy, Manson said.

There is no definitive timeline for when the new DAPY could be released, she said.

The R278474 compound is an upgrade of an earlier DAPY, TMC-125, which is currently in Phase II of testing to determine proper dosage. Once the dosage is determined, it will proceed to Phase III, the large scale safety and efficacy trials that the FDA focuses on, Manson said.

Ryan Lee can be reached at rlee@sovo.com.