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Biotech / Medical : Agouron Pharmaceuticals (AGPH) -- Ignore unavailable to you. Want to Upgrade?

To: JOHN W. who wrote (3826)	2/14/1998 9:50:00 PM
From: Henry Niman	Read Replies (1) \| Respond to of 6136

John, I just ran across this article that appeared in the online version of Business Week. It suggested that the altered metabolism associated with PI's may be quite high (over 60%), and even offered a mechanism, cross reactivity between a region on the protease targeted by PI's and a liver enzyme involved with fat metabolism (not something that I would put in the "insignificant" category): BUSINESS WEEK ONLINE February 5, 1998 NEW SIDE EFFECTS FROM AIDS DRUGS RAISE CONCERNS Edited by Douglas Harbrecht Potent new drugs have been a major success story in the treatment of AIDS. In many patients, drug combinations that include so-called protease inhibitors have kept the virus at bay for two years or longer. But now, worrisome side effects are beginning to appear. At the 5th AIDS Conference in Chicago, research groups from Australia, Canada, and the U.S. reported a bizarre phenomenon: Patients taking the drugs are beginning to look different. Their normal facial fat is disappearing. Meanwhile, fat is accumulating on their waists, neck, or back. "Patients are coming to their clinicians and saying: 'Hey, I don't look right,'" says Dr. John W. Mellors of the University of Pittsburgh. AIDS patients have even come up with a moniker for the condition: Crixbelly. (Crix is shorthand for one of the protease inhibitor drugs, Crixivan.) The most striking report at the meeting came from David Cooper of the Australian National Centre in HIV Epidemiology & Clinical Research in Sydney. Nearly two-thirds of his patients are experiencing the strange changes in fat distribution. "The data from David Cooper's group has really struck all of us," says Dr. Scott Hammer of Beth Israel Deaconess Medical Center. The changes in fat aren't just a cosmetic issue. Researchers believe they stem from a fundamental and potentially worrisome change in body metabolism. Indeed, the changes seem to be related to additional symptoms such as insulin resistance -- possibly leading to full-blown diabetes -- and elevated blood levels of cholesterol and trigylcerides. That might eventually lead to more heart disease. So it's no wonder that AIDS researchers are concerned. "Our excitement over the success of the drugs must now be tempered by these long-term toxicities," admits Hammer. Since the side effects became apparent only recently, researchers don't yet know how serious they will prove to be. Scientists are also a long way from understanding what's going wrong. At the meeting, however, Cooper's group suggested one possible mechanism. The Australian team discovered that the region of HIV's protease enzyme which is attacked by the protease inhibitor drugs is remarkably similar to part of a receptor on the surface of some liver cells. The normal function of these liver cells is to grab fat that's circulating in the blood. The protease inhibitor drugs, therefore, may be blocking this normal function by binding to the cells' receptors. Researchers speculate that this might explain why blood levels of triglycerides and cholesterol rise in patients taking the drugs. But they still have to figure out if this mechanism -- or some other -- explains the striking changes in body fat distribution or the increase in insulin resistance and diabetes. Until this puzzle is solved, "we won't know what the true risks are," says Hammer. "But now, this is a real concern." By John Carey at the 5th Conference on Retroviruses and Opportunistic Infections in Chicago