Researchers may finally be on track to fight the AIDS virus by blocking a long-elusive target, an HIV enzyme called integrase. An experimental drug that inhibits the enzyme helped to keep the infection in check in monkeys.

Far more research is needed to prove if Merck & Co.‘s approach really can block this enzyme’s crucial work in helping HIV reproduce and spread. After all, years of attempts at targeting integrase have failed.

In a study published Thursday in the journal Science, Merck reports that an integrase inhibitor dramatically protected monkeys when the drug was given early in infection. The drug also provided some benefit to the very sick.

Merck is studying some integrase inhibitor candidates in a few people to see whether the pills seem safe and to check for any early signs of viral suppression. Results, due by early next year, will determine whether larger studies should be performed on the prospective drugs.

The results with monkeys have leading AIDS researchers closely watching to see whether this new mode of attack might finally be possible.

“At long last,” was the initial reaction from Dr. Anthony Fauci, who heads the National Institute of Allergy and Infectious Diseases.

“I don’t want your readers to think I’m doing cartwheels over this,” he said. But, he added, “This is the next step in the process that the field, myself included, has been looking for, for some time now. It’s a very important target.”

Targeting integrase

There are two approaches to fighting HIV. One new drug, called Fuzeon, works by preventing HIV from invading immune-system cells.

Numerous older drugs work after the virus has invaded those cells, by blocking two of the three enzymes - reverse transcriptase and protease - that HIV uses to incorporate its genes into cells and to spread.

Combinations of those drugs have helped thousands of patients live longer and healthier. But these drugs are not a cure and they gradually lose their effectiveness.

So new approaches are needed, especially as the epidemic continues to rise. The United Nations counts a record 5 million people worldwide infected by HIV last year, with 3 million killed.

That explains the interest in the third enzyme, integrase, which is crucial to the actual melding of HIV genes with patients’ own DNA. Fauci said that step is vital to HIV’s sneakiest trait - its ability to hide inside cells so it can rebound after therapy.

Blocking integrase has proved extremely difficult. Just last year, GlaxoSmithKline and Japan’s Shionogi & Co. abandoned one experimental integrase inhibitor after initial human studies and returned to the lab to search for stronger candidates.

Glaxo would not give details. A spokesman, Rick Koenig, said, “We believe HIV integrase is a promising target. That’s why we continue to pursue it. That said, proof will only come with large clinical studies.”

Merck researchers gave their candidate, code-named L-870812, to six monkeys newly infected with a combination monkey-human version of HIV. The animals experienced only a mild decrease in crucial immune cells called CD4s, and four had their virus drop to undetectable levels, lead researchers Daria Hazuda and Steven Young reported.

Six untreated monkeys saw their CD4 levels plummet and viral levels soar. Almost three months later, Hazuda treated those very ill monkeys. All improved somewhat, but did not rebound nearly as well, or for as long, as the newly infected monkeys.

Hazuda said drug-caused viral suppression apparently worked more in concert with a monkey’s immune system when it had not yet been ravaged, allowing the body to fight back better.