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New Class of AIDS Drugs on the Horizon

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WebMD Health News

Jan. 27, 2000 (Atlanta) -- Discovery of the second member of a new class of HIV drugs promises to greatly expand AIDS treatment options -- someday. Merck researchers report in the journal Science that they have identified a class of compounds that specifically attack integrase, an enzyme crucial for HIV to reproduce in the body.

Current AIDS drugs also attack key HIV enzymes at various stages of viral reproduction. Protease inhibitors attack the enzyme needed to break HIV building blocks into correct sizes; reverse transcriptase inhibitors prevent the virus from turning its RNA into the DNA needed to take over cells. Now integrase inhibitors promise to prevent HIV from snipping open human DNA and inserting its own genetic code. A combination of the three types of drugs theoretically would increase the potency of AIDS drug cocktails.

HIV becomes resistant to any single drug. A combination of drugs, the so-called AIDS cocktails, combats this problem. However, the virus eventually becomes resistant to these as well. The hope is that by adding this new type of drug, the cocktails will become vastly more effective.

The first integrase inhibitor was reported on at the 1996 international AIDS conference by W. Edward Robinson, MD, PhD, of the University of California, Irvine. These compounds were first isolated from plants of the Kallawaya people of Bolivia.

"We are encouraged ... but it is in the very, very early stages of development," Merck spokesperson Laurence Hirsch, MD, tells WebMD. "We are a long way from having a new treatment for AIDS."

The findings, nevertheless, are stirring a great deal of interest. The search has been stymied by the lack of a test that can identify true integrase inhibitors. But now Merck researchers Daria J. Hazuda, PhD, and colleagues report that they have developed just such a test -- and that screening of more than 250,000 compounds led to the discovery of the new class of drugs.

"I think it sounds very promising," retroviral integrase expert Samson Chow, PhD, tells WebMD in an interview to provide objective comment. "These compounds are active specifically against integrase and can block HIV replication. You have a whole new class of inhibitors now. Also, it is very important that viruses with resistance mutations to protease and reverse transcriptase inhibitors are sensitive to integrase. This opens up the possibility of a whole new combination treatment regimen."

Robinson tells WebMD that the new paper confirms that integrase is an exciting target for AIDS therapies because it offers a new type of drug to use in combination with existing drugs. Indeed, studies in his laboratory show that the effect with the other two types of AIDS drugs has "at least additive" anti-HIV effect.

"Integrase is a viable target for drug therapy, and we are likely to see integrase inhibitors in clinical trials in the next few years," Robinson says.

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