Offering a promising new way to attack the AIDS virus, research on monkeys suggests that an experimental drug helps keep HIV in check by blocking an enzyme that is crucial to infection.
The target is integrase, an HIV enzyme that the virus needs to hijack a patient's cells and spread. Repeated attempts to inhibit integrase's function have failed.
But Merck & Co. researchers reported yesterday in Science that they developed an integrase inhibitor that significantly protected monkeys when given early in the infection's course and provided some benefit to the very sick.
Merck is testing integrase inhibitors on a handful of human subjects to see whether the pills seem safe and to check for any early signs of viral suppression. Results, due early next year, will determine whether larger studies should be performed on any of the prospective inhibitors.
Far more research is needed, but the monkey results have leading AIDS researchers watching to see whether attacking integrase might finally be possible.
"At long last," said Dr. Anthony Fauci of the National Institute of Allergy and Infectious Diseases.
Fauci said, "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."
There are two current 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 so it can use them to reproduce and spread.
Combinations of those drugs have helped thousands of patients live longer and healthier lives, but they aren't a cure and gradually lose their effectiveness. The UN counts a record 5 million people worldwide infected by HIV last year, and 3 million killed by AIDS.
That has led researchers to study the third enzyme, integrase, which is crucial to the actual melding of HIV genes with patients' own DNA. Fauci said that step is crucial to HIV's sneakiest trait, its ability to hide inside cells so it can rebound after therapy.
Just last year, GlaxoSmithKline and Japan's Shionogi & Co. abandoned one experimental integrase inhibitor after initial human studies, going back to the lab to search for stronger candidates.
Glaxo wouldn't give details, but "we believe HIV integrase is a promising target; that's why we continue to pursue it," said spokesman Rick Koenig. "That said, proof will only come with large clinical studies."
Merck researchers gave their substance 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 report.
Six untreated monkeys, in contrast, saw their CD4 levels plummet and viral levels soar. Almost three months later, Hazuda treated those very ill monkeys. All improved somewhat, but didn't rebound nearly as well or for as long as the newly infected monkeys.
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