Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
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Newsday - July 2, 1998
Laurie Garrett - Staff Correspondent
Dr. David Cooper of St. Vincent's Hospital in Sydney finds that more than half of his 3,000 HIV patients who are on protease inhibitors suffer dangerously elevated cholesterol and triglyceride levels, as well as extreme redistributions of their body fat.
"It's a syndrome of peripheral fat wasting, changes in body shape, hyperlipidemia, elevated cholesterol in the ranges where if you saw a cardiologist you'd immediately be put on cholesterol-lowering drugs," Cooper explained yesterday at the 12th World Conference on AIDS.
Some researchers, as well as protease inhibitor manufacturers, have suggested that there's nothing new about this syndrome - it existed in HIV patients long before the new drugs were in use. Cooper will have nothing of that notion.
"I don't believe we saw this sort of thing before proteases," Cooper insisted in an interview.
Among those who think the syndrome predates the drugs is Dr. Donald Kotler of Manhattan, who believes the lipid disorders are simply to be expected as a patient heals, regardless of the drug treatment. But others disagree.
"These patients have undetectable [HIV] viral loads and triglycerides in the sky. People should avoid denial, for goodness sake," Cooper said.
Rather than ignore the problem, Cooper has embraced it, hoping to determine the cause of the bizarre phenomenon. So, he turned to a super computer that contained the genetic sequences of millions of compounds normally found in the human body. He came up with two human proteins that share more than half of their genes with the HIV protease: cytoplasmic retinoic acid binding protein type 1 - or CRABP-1 - and low-density lipoprotein receptor related protein, or LRP.
Both CRABP-1 and LRP play critical roles in the body's metabolism of fat, cholesterol and triglycerides and its formation of diabetes. If CRABP-1 isn't around to do its job, Cooper said, masses of fat cells melt away, which could explain the spindly arms and legs people get who are on the protease inhibitors. Cooper's idea is that the drugs, drifting about in the bloodstream, are searching for their HIV target. But CRABP-1 and LRP look so much like the HIV molecule that the drugs end up attaching themselves to the wrong targets.
"And the result," Cooper said, "is that if the peripheral [arm and leg] fat can't go where it's supposed to go, it goes to central fat - the large paunches, big breasts and so on that we see with these patients," Cooper said in a speech.
Cooper denounced the "Vancouver hype" about the drugs, referring to euphoric statements released at the last World AIDS Conference in 1996.
A team of Brazilian researchers from the Medical School of Ribeirao presented evidence yesterday that patients on these medicines secrete in their urine large amounts of retinol and alpha-tocophenol, two vitamins never usually excreted from the body. These could be biproducts of Cooper's hypothesized retinoic acid problem - CRABP-1 misfunction.
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