The Big Tease | continued

On the front lines of AIDS care today, physicians -- under pressure by AIDS activists and a population living with a reputed "death sentence" -- have of necessity offered the treatment options that researchers say offer the greatest hope. Despite the expense, the controversy or the potential down side of the therapies, most American AIDS patients have access to protease inhibitors if they and their doctors deem them necessary.

The drugs' extreme costs have led to an unprecedented raiding of public funding coffers. As Lawrence Fox from the National Institutes of Health Division of AIDS noted, "From a public health point of view, the cost of protease inhibitors is enormous. In states that provide assistance [such as Massachusetts], their budgets have been gobbled up by the costs of the drugs."

According to the Mass. Department of Public Health, Franklin and Hampshire Counties had a little over 1 percent of the state's total of 4,075 AIDS cases as of February. Hampden County, on the other hand, contains more than 10 percent of the state's AIDS patients.

In Hampden County, perhaps the most prominent AIDS care facility is the River Valley HIV Clinic in Holyoke, which now treats 150 AIDS patients. Forty of those are now on a protease inhibitor in "cocktail" combinations with other therapies like AZT and 3TC. Dr. Gary Reiter is the founder of the clinic and has been treating people with AIDS since 1981, when he was based in San Francisco. "I see that we have really come a long, long way since the early days," he said. "I've found protease inhibitors in general to be an extremely effective therapy -- and remember what he have now is just the first generation of these new drugs."

He remarked that, despite the prohibitive cost of the medications, he could think of no instance when a patient for whom he prescribed protease inhibitors could not get them through some combination of private insurance, Medicare, Medicaid and the Massachusetts HIV Drug Assistance Program.

Closer still to the frontlines, Dr. Donald Abrams is the assistant director of the AIDS Program of San Francisco General Hospital, one of the most prominent AIDS care facilities in the world.

Abrams does prescribe protease inhibitors, but he is cautious in holding out too much hope for the drugs. "I do wonder exactly what it means in the long run for the patients," he noted. "People can get into the mindset of 'It's the virus, stupid' without remembering that it's the patient's well-being that should be foremost."

He's also wary of the claims that the introduction of protease inhibitors is somehow related to the recently announced decline in AIDS rates in New York City. "Let's not forget that the epidemic peaked in 1993," he observed. "That predates the introduction of protease inhibitors, which were released to the public in 1995."

In addition to running NIH studies, Lederman runs an AIDS clinic at the University Hospitals of Cleveland, where he prescribes protease inhibitors for his patients. Like Rasnick, he doesn't know of any clinical studies that show protease inhibitors' reported efficacy in helping an AIDS patient live a longer or better life.

"There have been none published to date," he said.

The problem, he asserted, is that studies to determine the so-called "clinical endpoints" take too long when, as he put it, "people are dying."

"Presently, I'm persuaded that benefits of these therapies are important, and I'm not going to wait for clinical trials to use them," he said.

In early 1996, one study did trumpet an impressive decrease in mortality rates for patients on protease inhibitors over a six month period. Abbott Laboratories -- which makes the protease inhibitor ritonavir -- announced a 50 percent survival rate of protease inhibitor patients over the placebo controls. The study was front-page news, but one year later it still has yet to be released for any outside scrutiny or peer review.

More important, after Abbott had collected data for six months more, the study did not make headlines. And in the final analysis, that may be more newsworthy than the preliminary presentation. Rasnick was at the 11th International Conference on AIDS in Vancouver where Abbott gave the rundown on its year-long study-in-progress.

"If there was anything to it, we should have heard about how the percentages are really holding up: 50 percent saved and all that," Rasnick noted. Instead, the cause for celebration six months earlier was all but forgotten -- morbidity and mortality rates weren't even addressed.

Even if Abbott's initial spike in the first six months on the drug turns out to be real, some longer clinical studies indicate that patients on protease inhibitors end up doing no better than the placebo controls, if that.

For instance, Rasnick was at a 1994 conference where one pharmaceutical company had funded 18 months of a protease inhibitor clinical trial -- with the drug saquinavir, in this case -- and a scientist on the team was presenting the results. "About the third sentence out of his month after he introduced the study was 'There was no clinical difference between the treated and the controls,'" Rasnick marveled. "No morbidity and mortality difference between them. They were also looking at surrogate markers [i.e. "viral load" and CD4 count], but nobody gives a damn about surrogate markers if the clinical endpoints aren't there.

"This study got published too," he continued. "But they didn't include the clinical data, only the surrogate marker data. And that's not uncommon in the drug world: Everybody publishes the favorable stuff and leaves all the other stuff out."

In some cases, protease inhibitor patients who stay as healthy as the placebo controls are lucky indeed. One new phenomenon that protease inhibitors appear to have heralded is a precipitous decline in health without any warning -- as documented in the Dec. 6 Newsweek cover story on protease inhibitors. The origins of this sudden downturn syndrome, also known as "crashing," are unknown.

The combined toxicity of the drug cocktails are certainly a source of concern. As Rasnick observed, "Crixivan from Merck crystallizes out the kidney and causes kidney stones. You can have renal failure with these things. Ritonavir stops the liver enzymes so the heightened toxicity of all the other drugs mount up and patients can die in a couple of days. You can save them if they're in a hospital at the time when they have these effects. Then you take them off the drugs, you take them off of everything, and you treat them for the toxicity of the liver. And you hope that the liver hasn't been destroyed to the point that it's irreversible. This is the dark side of protease inhibitors."

Seeing the "dark side" firsthand was only one of a host of circumstances that made Rasnick first begin to question Gallo's HIV-causes-AIDS hypothesis.

"Nothing made sense," he recalls. "It was just one thing after another," he said. For instance, the virus could scarcely be found -- let alone in levels sufficient to cause disease: "You try to ask people how many viral particles you find in the infected patients -- you can't find any in them. The virus isn't active."

Furthermore, "HIV tests" have never been specific to HIV. That is, they have been shown to give false positive readings for people with the flu, arthritis, lupus or with exposure to diseases such as tuberculosis, hepatitis and malaria. Even pregnancy or prior pregnancy has produced "HIV positive" responses. To top it off, the test actually indicates the presence of antibodies, which with every other virus has been the sign of a healthy immune system responding to infection. As Rasnick put it, "AIDS is the only disease where if you have antibodies to the virus it's a death sentence. I've got antibodies to smallpox -- I'm happy about that. That means I won't get smallpox. I've got antibodies to measles -- I'm happy about that. That means I won't get measles."

Rasnick has found the climate for addressing these concerns, however, to be anywhere from unfriendly to downright hysterical. He has co-authored papers with Duesberg and says he is disgusted by the response of the scientific community to Duesberg's research: "Peter Duesberg is one of the premier scientists in the world. He was a hair's breadth from getting a Nobel Prize. Yet as a result of his stand on HIV, all of a sudden overnight he's a fool, he's incompetent."

"It's almost like clinical McCarthyism," Rasnick observed. "It's a system completely out of kilter. AIDS is a sociological phenomenon. It's not a scientific issue, it's not a medical issue. I mean, we are looking at mass hysteria here. A train without breaks going down a mountain. And if you try to put rationality to it, you won't find it. It ain't there."

The entirely unscientific response to HIV-AIDS dissidents was in fact one of the reasons Rasnick began to suspect that the doubters may be onto something after all.

"All of a sudden, we can't do what scientists do anymore," he noted. "Scientists raise Cain. We're skeptical. We're critical. In the days of AIDS, though, skepticism is gone. Now it's to the point where you could get hurt professionally or financially or your career could be in jeopardy if you challenge the HIV hypothesis.

"It's almost like a religious thing. There are some things that you just can't talk about anymore. And that's not science. That's something else."