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Cocktail Hangover

Alarming new problems with the miracle protease inhibitors suggest that the euphoria over the end of the AIDS epidemic was premature.


It was just 6:45 A.M. when two dozen people mounted a bus outside St. Vincents hospital, with their coffees and placards and memories of Steve Michael, the AIDS activist whose body now lay in a satin-lined box in Washington, D.C. Michael had once run for president on a ticket he called "The AIDS Cure Party," and he actually made it onto the ballot in Tennessee. His final request was that comrades confront the White House with his corpse -- an activist even beyond death. In silence, his pallbearers carried him across Pennsylvania Avenue under a cottony sky, and at precisely 12:30 they swung open the casket lid. He was wearing an ACT UP T-shirt and a dozen KS lesions.

It was a scene right out of an old AIDS playbook. But it took place two weeks ago -- the same day, coincidentally, that news of a preventive-vaccine trial was on the front page of the Times. The funeral was a grim signal that at a time when AIDS is supposed to be in full retreat, all is not what it seems.

In fact, when the curtain lifts on the International AIDS Conference in Geneva later this month, there is going to be some surprisingly gloomy news. Researchers will present evidence that not everybody taking the new protease inhibitors is responding miraculously. According to two surveys, more than 50 percent still have detectable virus. Even many of those who saw an initial drop in their viral load and an increase in their T-cells are now watching that progress slowly reverse itself. "Christ Almighty, we had people thinking the cure was in hand," says Dr. Bob Gallo, the co-discoverer of HIV. "This is wrong."

The perception of a bright future has plunged the AIDS infrastructure into disarray. Fund-raising at major organizations like GMHC has fallen off, forcing large-scale cutbacks and layoffs, and the media have focused on other crises. The news from Geneva, then, could come as a much-needed shock. What seemed like the end of the AIDS epidemic may only have been the eerie eye of the storm.

There are many reasons the cocktails have been failing. They require dozens of pills on punishing schedules -- some every eight hours, some every twelve; some on a full stomach, some after fasting. In its July issue, POZ magazine reports that 18 percent of HIV-positive people surveyed got so bollixed in the past six months that they declared a "drug holiday" ranging from several days to a month or longer. But even a few missed doses can allow HIV -- cunning, ruthless HIV -- an opportunity to mutate. There is no surer cause of drug resistance.

Resistance to one protease inhibitor may mean resistance to others. The study of pill progression -- sometimes called salvage therapy -- is one of the vaguest areas of AIDS treatment. And to make matters worse, according to a Harris poll of doctors conducted earlier this month, fully one in four physicians doesn't prescribe the drugs properly.

Other patients are forced off their cocktails because of bizarre new side effects, from heart disease and diabetes to "lipodystrophy" -- a nasty accumulation of fat on the back and stomach, accompanied by wasting of the arms and legs. Even among the most successful population -- people who have never taken a single anti-viral agent -- there is a failure rate of 20 percent.

Sadly, the rate is highest for people with longstanding infections, those tenacious patients who used every drug in the arsenal over the years, waiting for a breakthrough like protease drugs. In one study, 70 percent of those "pretreated" patients did not succeed in suppressing their virus to below detectable levels, which is how success is measured.

Probably the grimmest revelation is that the virus continues replicating even in people whose viral load has remained below detectable levels for years. It had been hoped that the cocktails were eliminating all virus from the blood, leaving only inconsequential amounts inside immune-system cells. Since these cells die every few years, in theory the patient might eventually be entirely virus-free. But on May 26, the Proceedings of the National Academy of Sciences reported that HIV easily hides in previously undiscovered crannies of the immune system. These "reservoir cells" allow it to replicate continually, and they can take ten or twenty years to die. There are no new drugs in the pipeline capable of attacking those remote bunkers.

As a result, no one can safely stop taking the medications without fear of a recurrence of the lethal virus. But the medications may be too toxic for lifelong use. "Even if they want to stay on drugs that long, we don't know if they can," says Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. "It's sobering."

This is not to dispute the fact that the cocktails -- introduced so stunningly at the last world AIDS conference in Vancouver in 1996 -- have changed the course of the epidemic entirely. Opportunistic infections that had once defined the disease are disappearing: 70 percent fewer cases of AIDS-related pneumonia; 83 percent reduction in CMV retinitis; Kaposi's sarcoma practically vanished. Death rates have plunged, and Lazarus stories have literally reached biblical proportions (last month, Magic Johnson's wife told 60 Minutes that prayer, not protease pills, had "cured" her husband).

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