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Cocktail Time 

New U.S. guidelines suggest that powerful anti-viral drug combinations should be used later, rather than earlier, in treating AIDS

Wednesday, Jan 3 2001
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In a "To Our Readers" column accompanying its 1996 Man of the Year issue, Time magazine President Bruce Hallet noted that the man in question, AIDS researcher David Ho, panicked upon learning what his interviewers had in mind.

"Does that mean I'm Man of the Year?" Ho gulped (as observed by Hallet). "That makes me very uncomfortable."

Not to worry, Hallet wrote; Ho "relaxed when convinced that his experiments with the new antiviral "cocktails' would not be touted as a "cure.'"

The doctor shouldn't have been so easily assuaged. Time's Man of the Year package may have accurately depicted Ho's research, which showed that a narrowly defined group of AIDS patients responded well to a combination of anti-virus medicines. But Ho's lionization spawned a virus of global hyperbole that rapidly spread through the media, mutating, it seemed, with every transmission.

By dawn the next day, the story of Ho's new status was appearing in papers all over the world without the specificity or the subtlety of Time's 7,000-word Man of the Year opus. The Scotsman in Edinburgh, like papers everywhere, posed the headline question, "Can this man wipe out AIDS?" It left readers to surmise, "Perhaps."

What happened next -- a near half-decade of medical missteps, a plague of unnecessary suffering resulting from inappropriate early use of toxic anti-viral drugs, and wave upon wave of confusion, dissension, and despair among doctors and their patients -- actually amounts to the best Western medicine's got when it comes to battling an unfathomable disease such as AIDS. That's because the progress of medicine is more -- or less, depending upon how you look at it -- than just high science. It's high science filtered through journalism, scientific dissent, and a constantly changing state of the curative art. The resulting serum is injected into the doctor-patient relationship, and informs thousands of medical decisions, some lifesaving, others disastrous.

This month, the federal government will issue AIDS treatment guidelines that represent a partial repudiation of science described in that early Time article. How the medical establishment arrived at this new state of common wisdom during the previous four years is an apt illustration of the constructive and destructive ways culture informs the manner in which doctors treat patients.


Ho had rejected the common view that the AIDS virus lay dormant for a period before attacking the body, saying the body and the virus are actually locked in a pitched battle from infection on. Therefore, he theorized, it was best to attack the illness as early as possible with a highly toxic dose of medicines, including newly developed protease inhibitors, which stopped the virus from making copies of itself. By hitting the virus early enough, and hard enough, it was believed that it might be possible to completely wipe it out. AIDS, it was briefly believed, might soon be cured.

"That was a brief period of euphoria after a long period of dark despair," recalls Paul Volberding, professor of medicine at UCSF and director of the Positive Health program at San Francisco General Hospital.

It's been four years since that false AIDS spring of 1996, and American ideas about treatment of the disease have traveled a long, circuitous route. Researchers found they couldn't actually eradicate the disease, but only beat the AIDS virus back to manageable levels. They found that anti-viral cocktails cause fat to collect in some people's bodies in bizarre ways, creating bowling-pin torsos and buffalo-hump-like necks. They encountered patients with neurological problems, diabetic symptoms, anemia, headaches, nausea, weight loss, dry mouth, and hair loss -- all symptoms associated with AIDS drugs. The side effects of AIDS treatment, it was learned, can themselves cost thousands of dollars per year to treat.

Doctors also found that it can be devilishly difficult to keep patients on complicated drug regimens -- particularly when the drugs cause severe side effects, while the disease those drugs are supposedly treating isn't yet showing significant symptoms. Perhaps most frustratingly, they discovered that the lingering news cycle left over from the false AIDS spring had led some gay men to justify being less careful about their sex lives.

The cumulative result has caused the medical establishment to back away from the hit-it-early, hit-it-hard doctrine. Doctors still agree it's necessary to use powerful medicines to beat back AIDS. But they no longer believe that it's always, or even usually, appropriate to attack the disease early. And some AIDS treatment experts are now acknowledging that a part of the focus on early treatment may have been driven more by hype than solid science, and that the early use of drugs with powerful side effects caused years of suffering that could, and should, have been avoided.

Next month, the U.S. Department of Health and Human Services will release a revised set of HIV treatment guidelines that represents the culmination of a four-year-long retreat from Dr. Ho's initial ideas about AIDS. The new guidelines are a significant shift of popular medical wisdom about the proper use of AIDS drugs. They will recommend holding back from using powerful anti-viral drugs until the immune systems of HIV patients show significant signs of decline. In essence, the guidelines acknowledge that the precipitous use of protease-inhibitor-laced anti-viral cocktails may actually do more harm than good.

According to the new guidelines, patients should not get "triple therapy" -- a protease inhibitor and two older anti-HIV drugs -- until the number of T-helper immune cells falls to fewer than 350 per milliliter of blood. The normal level is around 800. Older guidelines advise that triple therapy treatment should begin when T-helper cell levels fall to 500 per milliliter of blood.

"It's pretty much of a sea change," says Mark Harrington, senior policy director for Treatment Action Group, a New York-based advocacy organization.

"It's an accumulation of all the side effects we've seen," says Volberding, who's on the government committee that wrote the new federal guidelines. "There were neuropathologies, some suppression of red blood cells that would cause anemia. There were some drugs that caused kidney stones or skin rashes. There are a number of potential side effects, but it's not as if those are so horrendous we can't work with them; we do. But we recognize we don't need to use the medicines as early as we thought."

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Matt Smith

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