SCIENCE FICTION

By Celia Farber

Gear Magazine March 2000

In 1996 a scientist claimed he'd found a way to defeat AIDS. In the wave of euphoria that followed, a batch of new drugs flooded the market. Four years later, those drugs are wreaking unimaginable horror on the patients who dared to hope. What went wrong?

It's telling, and perfectly symbolic that when AIDS researcher David Ho's face appeared on the cover of Time as Man of the Year, 1996, you couldn't see his eyes. Instead, a colorful swirl meant to represent HIV filled his glasses. George Orwell used precisely this image -- a man whose eyes are gone, whose glasses have been filled with the refracting light of his ideology -- to convey the triumph of politics over truth in his famous essay Politics and the English Language.

Ho, the then newly appointed director of the Aaron Diamond AIDS Research Center in New York, was suddenly catapulted to a degree of fame that no other AIDS researcher had ever attained, and gave him an oracular power over the press and the AIDS community. The relentlessly driven son of Chinese immigrants, he was a man singularly obsessed with HIV, and his vision was to attack it with a ferocity never before imagined -- to bomb it with not one drug, or two, but a literal hail. He popularized and largely pioneered the idea that would make such pharmaceutical bombing seem rational -- that HIV, far from being the cryptic, latent, quiet virus most researchers thought it was -- was in fact "replicating furiously," from the very moment of infection. The immune system, he claimed, fought back valiantly, mass producing immune system cells in an effort to defend itself, but in the end, the virus would win the battle, and the immune system would collapse.

The only rational attack therefore, was to begin treatment as early as possible, to defeat the virus. He was a man of simple concepts, and the one that would alter history went like this: hit hard, hit early.

Ho's seductive experiment, which spread to newspapers around the world before it was ever completed, was to knock back HIV to the point of being "undetectable," then take the patients off the "cocktail" of drugs, with HIV, hopefully, banished for good. His recipe for a cure, a word that was heavily implied if semantically avoided, was to create a blitzkrieg of chemicals -- a mixture of old AIDS drugs like AZT with the new class of drugs waiting in the pipeline called "protease inhibitors" -- to annihilate HIV in the bloodstream. Protease inhibitors had been researched since the early 90s by the major drug companies, several of which came close to abandoning the effort because the drugs did not work against HIV.

But Ho was convinced that his new approach of mixing several drugs would work where no single drug had succeeded, and that curing AIDS was a simple matter of eradicating HIV.

Magazines and newspapers took Ho's central metaphor and reprinted it without a second thought: AIDS is like a full sink with the drain open; the water pours in from the tap at a slightly slower rate than it drains away. Eventually, the water -- the T-cells of the immune system -- will drain away enough to cause the immune collapse known as AIDS.

David Ho, Time magazine gushed, "fundamentally changed the way scientist looked at the AIDS virus... His pioneering experiments with protease inhibitors helped clarify how the virus ultimately overwhelms the immune system.

"Mathematical models suggest that patients caught early enough might be virus-free within two or three years."

David Ho, Time concluded, delivered "...what may be the most important fact about AIDS: it is not invincible."

Based largely on a single paper -- Ho's 1995 paper -- protease inhibitors received lightening-quick FDA approval and poured onto the market. The mass media declared AIDS to be "over," albeit with a question mark floating overhead. A new euphoria filled the air, and David Ho spawned a multibillion-dollar drug industry.

Amidst the excitement, something was overlooked.

Ho's mathematical model was wrong.

***

The phone rang late one night and Shawn O'Hearn, 33, a San Francisco HIV prevention worker, answered it. It was an old friend, a successful dancer who, although he had tested positive for HIV, had remained in perfect health. Following the advice of the nation's leading AIDS organizations, he had begun taking a cocktail of drugs including protease inhibitors, even though he didn't have any symptoms of disease. Four weeks later, he suffered a stroke.

"I'm paralyzed, Shawn," he told O'Hearn.

He'll never dance or even walk again.

This is not a rare story; it is a common one in the age of AIDS drug cocktails (as the combination treatments championed by Ho have become known). Such tragedies are seen as an inevitable "side effect" of a drug regimen so punishing that an entire surveillance system has been put in place to ensure that people stick to it. There are computer chips embedded in bottle caps that record the date and time of each opening. There are beepers, support groups, buddy systems, observation centers where patients take the drugs while being watched, and even groups of AIDS professionals who infiltrate people's social networks to enlist them to help promote and dispense the drugs. They call it "treatment compliance," and it has largely replaced Safe Sex as the core social imperative of the AIDS industry. The goal is to get as many HIV-positive people on the drugs as possible, whether they are sick or healthy, and to keep them on them, through debilitating ill effects, which are dismissed as a small price to pay for the benefit of lowering the amount of virus in the blood. But now, four years after the initial AIDS cocktail drug hype erupted, the utopian promise is fast turning into a nightmare.

"I started to notice that more and more friends, young people, were suffering these mysterious strokes and heart attacks," says O'Hearn, a member of the HIV Prevention Planning Council in San Francisco.

"They are listed as AIDS deaths. But those are not AIDS deaths, those are drug deaths."

San Francisco is a crucible for the new schism in the AIDS community. The city's AIDS culture has long been characterized and dominated by the mainstream organizations which advocate drug regimens for all HIV-positive people.

One group that stands in stark contrast is ACT UP San Francisco. The group has a clientele of about 1,200 people with HIV looking for advice, support, and medical marijuana to ease their pain. "What is going on?" I ask member David Pasquarelli. "What are you seeing?" He is quiet for a moment.

"Death and deformity," he says. "Deaths from strokes, heart attacks, and kidney failure. We've lost probably half a dozen clients from sudden deaths in the past year. We've also seen at least 30 people that have distended bellies and hunchbacks from taking the drugs.

"I had a guy come in just last week and he was crying. I said, 'What's wrong?' He said that his roommate of 10 years had died suddenly, after going on cocktail therapy."

There are facts and figures, studies and counter-studies, a virtual blizzard of data that could be arranged to show any number of things. The new AIDS drugs have saved people's lives: that's one piece of truth. The new AIDS drugs have killed people: that's another. The new AIDS drugs have damaged and deformed some people so badly that although they are alive, they wish they were dead.

"Everyone keeps saying these drugs are extending lives and saving lives and we're supposed to believe it," says Pasquarelli. "I had this woman on the phone today from HIV Plus magazine and she said, 'Protease inhibitors are causing people to live longer,' and I said, 'No they're not. Everybody who is taking protease inhibitors is contributing to one big medical experiment. And no one knows the outcome of it.'"

Pasquarelli's group recently unearthed a 1997 study by San Francisco Health Department director Mitch Katz which exposes a shocking statistic which would appear to dispel the claim that the cocktails have caused AIDS deaths to plummet. Using stored blood samples and computer analyses, the study, published in the Journal of AIDS and Human Retrovirology, concluded that new HIV antibody-positive diagnoses peaked in 1982 in San Francisco -- two years before HIV even had a name.

"There's a big problem in terms of looking at this as a contagious epidemic," says Pasquarelli. "HIV positive diagnoses for the past 13 years here have remained steady at 500 cases a year. People don't look at the chronology of this, or at the statistics. They just have it in their heads that these drugs save lives, and that's it." (Katz has since confirmed the group interpreted his data correctly.)

And, Pasquarelli points out, on a national level, AIDS deaths began dropping at the end of 1994, at least three years before the drugs hit the market, a fact no one disputes.

***

"There is absolutely no question whatsoever that protease inhibitors have helped people," says veteran AIDS doctor Joseph Sonnabend, co-founder of AmFAR, now practicing in New York's Greenwich Village. "But they've probably hurt more people than they've helped. That's why it's complicated. The people for whom benefit has been proven beyond a doubt are really sick people who would have died without them three years ago. But the target population for the drug companies are the healthy people, and those people will almost certainly have their lives shortened by these drugs."

It was precisely those healthy people who were the primary target of David Ho's eradication campaign. Time enthusiastically exhorted: "HIV-positive patients would have to start taking the drugs immediately after infection, before they realize they're sick." Ho's mantra, "Hit hard, hit early," ushered in a new machismo in AIDS treatment, where people seemed to measure their own self-worth by how long they could endure the devastating drugs.

"I have personally seen what was being called the Lazarus effect [where chronically ill people rise off their deathbeds]," says Dr. Michael Lange, chief of infectious diseases at St. Luke's-Roosevelt Hospital in New York. "But I would also say that many, many people are being badly harmed by them. Also, the regimens are so complex and hard to stick with."

"In my experience, I have seen that those who do not take any of these AIDS drugs are the ones who remain healthy and survive," says German physician Claus Koehnlein, who recently testified this past December at the trial of a Montreal woman who refused to give her HIV-positive children cocktail therapy, and then in a chilling Orwellian scenario, had them taken from her and placed in a foster home where they are being forced to take the drugs.

"I treat the individual symptoms -- the whole person, not just the virus. I treat them for whatever they are suffering from, and that's that. I have not lost a single patient in seven years and I've never used cocktail therapy."

Precisely what it means for a life to be "saved" is complicated, especially when the patient was not sick to begin with. As Koehnlein wryly commented, "If you treat completely healthy people you can claim great therapeutic success."

"The vast majority -- about 75 percent -- of people who go on these drugs are completely healthy," says Dr. Steven Miles, AIDS researcher and doctor at UCLA Medical Center.

"Large numbers of people are being inappropriately treated with drugs they don't need. And their lives are probably being shortened, yes."

At Lemuel Shattuck Hospital, Massachusetts, a review was done on every HIV-positive patient who died at the hospital between May 1998 and April 1999, and compared to a group of patients who died in 1991, before drug cocktails were available.

Of the 22 "post-cocktail" deaths, half died of liver toxicity from the drugs, and two more had liver toxicity listed as a secondary cause. The study concluded that liver toxicity was "now the leading cause of death among HIV-positive patients at our institution."

In other words, allegedly life-saving AIDS drugs are killing AIDS patients at this particular hospital.

Hospitals around the country are reporting radical increases in heart attacks, strokes, diabetes and other complications caused primarily by the drug's interference with the body's natural ability to metabolize fat. This is also causing the fat redistribution that leads to humpbacks and huge torso in men, and gigantic breasts in women. At the same time, fat disappears from the face, arms and legs, rendering patients stick-like.

Holly Melroe, a Registered Nurse at Regions Hospital in St. Paul, Minnesota, wrote last year in the Journal of the Association of Nurses in AIDS Care that the drug therapies "may have a greater life-threatening potential than the disease itself."

I spoke to Melroe to see if she would confirm that statement.

"Oh definitely," she said. "We are hospitalizing more people now for the side effects of the drugs, than we are for the infections of AIDS. It's a very complicated situation."

Up to 80 percent of those patients were found to have dangerously high cholesterol levels, which have led to heart attacks in many cases. When I comment that it seems strange for these drugs to continue to be referred to as "life-saving," she quickly says, "Oh, but they are."

The death rate, Melroe claims, has declined by 80 percent in Minnesota over the last four years.

Says Michael Bellefountaine of ACT UP San Francisco: "People are allowing their bodies to get to the point where they physically can't handle the pain anymore, because their neck is being forced downward with these humpbacks. Yet they will endure it, hoping that the government will pay for, you know, liposuction. You see plastic surgery ads in the Bay Area Reporter that say, 'Wasting away? We can make your cheeks look fuller.'

"It is absurd. Instead of telling people to get off the drugs, we tell them to get plastic surgery! One person told me he feels like his intestines are corroding from the inside out. These people can't stomach anything. They can't digest anything. They have internal organ failures. You hear stories of people who are on their way to work and they just drop dead from a heart attack.

"We are seeing people who have massive swelling in the face to the point that their eyes, if they are able to open them, are incredibly sunken. The cheeks and the forehead are pushed forward. They have these hard, bumpy calcium deposits. People are bruised, almost raccoon-like around the eyes. They look like walking skulls."

The group runs a medical marijuana dispensary out of its offices, thereby coming into contact with scores of people who are on cocktail drugs. They actively "intervene" and try to convince people to go off the drugs, citing among other things the fact that they -- the 100-odd members who adhere to their philosophy -- are all drug free and healthy for several years. But Bellefountaine says that the fear of HIV is too deeply rooted in most people. "People are still so afraid of what is going to happen if they don't take these drugs that they will remain on the regimens until they literally kill them," he says.

Shawn O'Hearn tested positive for HIV two years ago. He, too, went on a three-drug cocktail regimen. "I was trying to be a good little boy and make it through and stay on my regimen. I was taking almost 30 pills a day." Soon his body was covered in blisters, and he was suffering debilitating nausea. He quit the drugs after four weeks, and his health returned.

"I have many, many friends on these cocktail regimens," he says, "and some of them swear by them. But all I know is, I am seeing young people dying of very weird things that are not AIDS."

The new drugs, unlike the prior generation, AZT, DDI and D4T, are very specific in their ability to inhibit HIV's crucial protease. DNA and protein are the basics of life, and protease are what control the proteins, turn them on and off, process them and so forth.

The turning point for the new drugs came in 1995, when Ho and another scientist, Dr. George Shaw, co-authored a paper, published in the eminent scientific journal Nature, in which he detailed his new vision of HIV, AIDS and the immune system. On the day the paper was published, a press conference was held. The "new model" was coupled with the new drugs, and a new technology took center stage -- so-called viral load testing. Rather than focus on physical symptoms, the new craze was to take the drugs and measure your viral load (the amount of virus in the blood) and CD4 cells, now considered a barometer for the immune system's health. The new drug regimens were supposed to lower the former and raise the latter. The concept was: beat back the bad guys (HIV-infected cells), and the good guys (CD4 cells) will win.

The central puzzle of HIV research up until that point had been how the HIV virus could cause AIDS, when it infected only a trivial number of T-cells -- the cells AIDS patients were deficient in. As one researcher said, it was a crime scene with many more bodies than bullets.

One leading virologist who had won tremendous acclaim for having mapped the genetic structure of retroviruses and had been nominated for the Nobel Prize, Dr. Peter Duesberg of the University of California-Berkeley, was sufficiently troubled by this paradox of cell infection that he concluded HIV could not be the cause of AIDS. For his heretical questioning of the AIDS establishment, he was condemned, censored in the scientific literature, no longer funded, and sent into virtual scientific exile.

David Ho would never harbor such thoughts. In fact, his faith in HIV as the singular cause of AIDS was so deep that he produced buttons which he wore and distributed at an AIDS conference in 1995 that said "It's the Virus, Stupid" -- a direct stab at Duesberg.

***

Ho is not a mathematician, but nevertheless he contrived a mathematical model in consultation with other mathematicians, on which he would base his entire premise. The model was supposed to demonstrate that HIV killed healthy cells slightly faster than they were able to replenish themselves, but the math was so dubious that very few AIDS researchers could grasp it enough to either validate or reject it. Nobody bothered to try. Instead, it simply floated upward like a balloon of epiphany, the dawn of a new era.

The balloon of hope had many uses: HIV-positive people could hope for a new lease on life, the drug companies could sell drugs like never before, and even keep their customers convinced, through the AIDS care-network itself, that total compliance with this draconian discipline was the only path to heroic survival. Miss one pill, the new wisdom held, and HIV, enigmatically, will "mutate."

Ho, whose given name Da-I translates to "Great One," repeatedly declined to be interviewed for this story. Those who know him, or have met him, describe him on the one hand as "a nice guy," and on the other as a man totally bereft of personality. But whatever his personal characteristics, he certainly played a pivotal role in not just AIDS history but medical history.

It was at an AIDS science conference in Florida in the early 90s that Ho, then a virologist of no particular distinction at UCLA, heard a high-ranking chemist at Abbott Pharmaceuticals discuss protease inhibitor prototypes. Ho approached the chemist, Dale Kempf, on an airport check-in line, and told him he had a theory about "how the AIDS virus worked" and how much more ferocious it was than anybody realized.

"Dale agreed that maybe we could help each other," Ho later told the Wall Street Journal.

By 1993, Abbott had narrowed its hundreds of prospective compounds down to one, which later became the most toxic of the licensed protease inhibitors, Norvir.

Meanwhile, philanthropist widow Irene Diamond had fulfilled her late husbands Aaron Diamond's wish to set up a lavish research lab which would attract some of the best scientists in the country. "Irene wanted a star," is how Dr. Steven Miles describes it. She chose the quiet, diminutive David Ho to be the director of the institute, immediately after meeting him and hearing about his research.

Ho and his colleagues at Aaron Diamond, Dr. Marty Markowitz, began experimenting with a handful of patients. They gave them the cocktail therapy, measured their drug-resistant mutations, and then calculated "how man y virus particles were churned out each day by infected cells," according to Michael Waldholz, reporting in the Wall Street Journal. These calculations led to the infamous math model.

The problem is not restricted to the math model, however -- the very technique that Ho and Markowitz used to measure and calculate these "virus particles," is itself deeply problematic.

Is "viral load" really measuring the amount of virus in one's body? Not according to some of the scientists who have studied the matter closely. "The only important question in AIDS is how much infectious virus there is," says Harvey Bialy, editor-at-large of the journal Nature Biotechnology. "Despite all the noise about massive viremia [levels of virus] and math models coming in from David Ho, the figures remain precisely as Peter Duesberg published in 1987 when he first critiqued the hypothesis," Bialy says. "Only one in 100 T-cells are ever infected, only one in 1,000 are ever making viral proteins, and that corresponds to a tiny amount of virus present in the blood. Everything else is effectively neutralized by the immune system.

"A viral load of 100,000 corresponds to one or less virus particles, which is the only medically relevant barometer. That is not enough to do anything. In the Nature paper, Ho manipulated the picture by using PCR [a technique that massively amplifies DNA] and passed it off as infectious virus. When I read it, I said, 'This is fucking nonsense! How do you pass off a biochemical unit as an infectious particle? This will never fly. But it flew."

Dr. David Rasnick, a chemist who once worked in diagnostics at Abbott and is an expert on protease inhibitors, concurs with this view.

"'Viral load' is the most powerful microscope ever developed," he says. "If the only way you can see something is by using the most powerful microscope, how clinically relevant can it be? If a person had real viremia you wouldn't need PCR to see it. Here you're talking about a level of about one virus particle in a drop of blood!

"Here's an example. When they look for HIV in breast milk, they do 45 cycles of PCR, which is a 35-trillion-fold amplification, in order to find enough genetic material. We are at the level of sensitivity of nuclear physics now with this PCR stuff. And David Ho talks about making HIV 'undetectable?' It starts out undetectable. That's the whole point. HIV has always been more or less undetectable.

"So they've taken a number that is next to nothing, and mass multiplied it. But it's still next to nothing. Just a bunch of numbers that are used to scare people and make people go on these drugs.

"All this stuff about wanting to get to zero, or to undetectable, is absurd because it implies that a single particle of HIV is lethal, but it's not.

"This is the biological equivalent of counting bumpers in a junkyard and saying they represent functional cars."

***

In the summer of 1996, thousands listened to Ho's findings from TV monitors hanging through the vast conference halls at the International AIDS Conference in Vancouver. The audience listened with rapt attention as Ho revealed his data: nine patients, he said, who had been on a combination of drugs including some of the new protease inhibitors, had "no evidence of the virus in their bloodstream," after being on the drugs for between 90 and 300 days. Ho calmly repeated his mantra: because of the new drugs, it was "time to hit HIV, early and hard."

"It was just unadulterated hype. It was preposterous," recalls Dr. Steven Miles. "It was almost like an instantaneous religion, or a cult, right after Vancouver. You were either a part of that hit-hard-hit-early religion or you were not. It split the HIV community."

AIDS treatment was in a depressed state at this time. The results of a devastating study three years earlier had dashed the long-held belief that AZT could extend life -- instead, it was shown to shorten life. Many prominent researchers, deeply alarmed that they had unconsciously given a drug that had done more harm than good, were abandoning toxic drugs and looking to resolve the disease by stimulating the immune system instead.

But Ho's mathematical model which "demonstrated" that the virus was "furiously replicating," made the virus suddenly seem more lethal than ever, and in the fervor that followed, doctors who advocated being careful and conservative with drug regimens were seen as foolish pacifists, willfully surrendering to a vicious enemy.

A kind of collective fantasy formed in the hushed room at the Vancouver conference, as the low-key scientist unveiled his data, never altering his blank facial expression, but inspiring a mania with his quiet use of a few new buzzwords: "eradication," "undetectable." The fantasy was that the new drugs could eradicate HIV -- get rid of it -- and that once it was gone, people could stop taking the drugs and live AIDS-free for the rest of their lives. All agreed that these drugs were not designed for long term use, that they were way too toxic.

Ho cast a powerful spell over not just his audience, but the world's media, medical community, and AIDS community. The excitement that emanated from Ho's presentation was palpable -- it spread like wildfire through the media. Within hours, people were rushing in to their doctors' offices, begging for prescriptions. Most of them were healthy. None of them cared about anything except the new magic word: eradication.

"It's not even really a mathematical model," says Mark Craddock, a mathematician at the University of Technology-Sydney, referring to Ho's construct. "In my opinion, it's mathematical junk."

Craddock has written several critiques of Ho's model, and says he cannot comprehend how it was ever able to gain such momentum. "Ho's equations predict that over the course of 10 years, an HIV-positive person will produce more particles of HIV than there are atoms in the universe. There is no way you could make that much virus."

Mathematical modeling of diseases is a whole area of research unto itself. "It is widely acknowledged in the mathematical biology community," says Craddock, "that AIDS has been damn near impossible to mathematically model properly. No one has succeeded in producing a model that even looks right.

"The history of mathematics is full of things that looked right but turned out to be wrong. That is why we insist on proof. You have to check every single detail and make sure it is right. We send a Voyager spacecraft out, and it arrives within a few minutes of predictions at the planet Neptune twenty years after it departed. That is because Newton's theory of gravitation works."

An editorial in the February 1998 issue of Nature Medicine by renowned virologist Mario Roederer pointed out that cocktail therapy does not cause T-cells to increase, but rather to be redistributed throughout the body -- which is not an immunological advantage. This had been discovered a year earlier when an American group of researchers developed a way to "tag" newly synthesized DNA and isolate T-cell populations. What they found does not bode well for those who are on cocktail drugs: of three groups -- uninfected people, untreated HIV-positive people, and HIV-positive people on the drugs -- the T-cells of the ones on the drugs survived the shortest amount of time.

"You don't have to waste a lot of time on this," says Bialy when I ask him about how and when Ho's research was refuted in the scientific literature. "The Roederer piece finished it. Ho is finished. In the scientific world right now it is firmly established that the model is nonsense."

One AIDS researcher and physician who spoke only on condition of anonymity had this to say about Ho's theory: "Everybody in the scientific community has known for years that his HIV model was ludicrously wrong. I remember being at a conference in Chicago two years ago, and Ho's data was shot to shreds by one speaker after another. David Ho got up to speak at the end and there was really nothing he could say."

Several researchers contacted for this piece, even those who had disputed Ho's findings in print, refused to comment on Ho as a scientist. Others were less intimated -- or, like Joe Sonnabend, have already been punished for speaking their mind (Sonnabend has fallen out with two major AIDS organizations he once worked with) and have nothing left to lose.

Sonnabend scowls when I ask about Ho's math model. "Of course it's wrong," he says impatiently. "Everybody knows that. It's such way-out bullshit. The notion of 'eradication' is just total science fiction. Every retrovirologist knows this. The RNA of retroviruses turns into DNA and becomes part of us. It's part of our being. You can't ever get rid of it."

I told Sonnabend that I had heard from researchers -- none of whom would go on the record -- that Ho had committed what some were calling, at the very least, spurious research, by withholding a vital finding from the data. In his experiments, Ho had shown that protease inhibitors, by stopping HIV allowed healthy CD4 cells to flourish. But what he didn't reveal was that CD8 cells (which have nothing to do with HIV) also increased.

"Yes, he's a fraud," Sonnabend says, "if a fraud means mediocre interpretations of the dynamics of T-cell changes in response to therapy. But, then, who is the fraud? Anybody is capable of having stupid ideas, but what's unusual is getting them onto the front page of the New York Times and Time. The real villains are the people in your profession, in my opinion. The journalists. We have traditionally depended on the press to protect us from nonsense like this -- not anymore.

"Now people who have feet of clay become oracles thanks to their publicists and the cooperation of journalists. And the real tragedy is that years have been wasted on this David Ho eradication hype. What he did was unspeakable. To dangle a cure in front of such desperate people is the cruelest thing imaginable."

"I heard from a well-placed source that protease inhibitors were approved by the FDA, based on Ho's Nature paper," says David Rasnick. "There was certainly no clinical data that they were effective, and to this day there is still none."

***

The rush to get the new AIDS drugs on the market caused a near-total disintegration of the FDA drug approval process. Some of these drugs were approved in a matter of weeks, a process that normally takes years. But who was going to complain? Certainly not the recipients of the drugs. They would only complain if the drugs were not approved fast enough. So protease inhibitors were approved on small, short trials, in which results were virtually engineered. Data can be skewed to show anything under such circumstances. Some -- especially AIDS -- drugs these days are tested in the human population -- after they are released.

Toward the end of 1997, a study from Germany showed that almost half of those taking protease inhibitors had their virus levels increase, not decrease. The authors wrote: "The success seen in controlled studies is not necessarily reflected in everyday practice."

"These damn things were released without proper evaluation or testing," says Rasnick, who now devotes his time to warning people about protease inhibitors. "Whenever you give a drug, something that is biologically active, you're going to get some responses. You don't know whether it's going to be good, neutral or negative. You haven't a clue. That's why previously the FDA approval process was so laborious. It was to protect people against these unknowns, these toxicities."

A few years before protease inhibitors came onto the market, Rasnick attended a conference where a paper authored by a Dr. Paul Saftig, and published in the journal EMBO, was presented. It had no relationship to AIDS, but nonetheless stayed vivid in his memory.

It was a so-called "knock-out" experiment, in which scientists totally erase a gene from an animal, and then gauge what effect it has. The gene is erased from either a fertilized or non-fertilized egg then implanted, and then the resulting offspring, if there are any, are studied. "Typically what happens," says Rasnick, "is that either the animals are born with absolutely no difference that you detect, or, you don't get any offspring at all."

But this experiment was highly unusual. In it, scientists removed an aspartyl protease known as cathepsin D -- one that all humans have -- from the mice. The mice were all born normal, and for the first three weeks of their lives, appeared to be thriving. But on the 21st day, every last one of them died.

Autopsies showed that the mice had starved to death. "Their intestines were completely destroyed," says Rasnick. "Also, they had what the authors called fulminate loss of T-cells and B-cells. In other words, their immune systems were shot.

"That study was a real red flag," says Rasnick. "Cathepsin D is the only protease I know that is absolutely essential for life, so you'd want to stay away from it. I remember thinking to myself at the time, thank God we are not working on aspartyl proteases, or making inhibitors for them."

When Rasnick began hearing stories of the chronic diarrhea and wasting syndrome that was among many problems to afflict people on the new protease inhibitors, he had a sinking feeling.

"I said, 'Oh shit, it's happening.' You see, there's always crossover. Even though it's not the target, all of these protease inhibitors also inhibit cathepsin D. The same aspartyl protease that they knocked out in the mice."

"And they're giving people up to seven grams a day of this stuff. I don't see how anybody can survive that in the long run. I'd love to see some post-mortems done on these guys who die on cocktails. I'd like to see what their intestines look like."

Rasnick believes it was a grave mistake for the FDA ever to approve protease inhibitors for human use.

"I would pull these protease inhibitors off the market based on the Saftig paper alone."

***

In March of last year, a gathering of the world's leading AIDS researchers convened, as they do each year, at the elite Chemotherapy of AIDS Conference, known as the Gordon Conference, in Ventura, California.

Nearly half of the 105 people attending were from within the pharmaceutical industry. David Ho was there, as was Martin Markowitz. Markowitz and Ho received a lot of publicity for their ongoing study of 27 people on HAART (Highly Active Antiretroviral Therapy) -- the multi-drug regimen that is now the standard of care for AIDS patients, both adults and children -- in fact, even pregnant women.

"At last year's conference, I asked Markowitz if his patients on HAART were doing better, the same, or worse while on the drugs," says Dr. Rasnick. 'He didn't say a word. He just stood there. I asked the question three times. This time I decided not to ask. If his patients had been doing well, I'm sure he would have let us all know, especially me."

Dr. William Cameron, an M.D. and consultant to the Canadian FDA, "completely demolished the viral load surrogate marker" as a relevant way to measure health or the success of treatments, according to Rasnick. He used as an example the clinical disaster, never reported in the media, of a drug many people were on years ago called DDI. Over a 12-week study, the drug worked brilliantly on viral load levels, but shortly thereafter turned out to be virulently toxic, in fact lethally so. At the highly private conference, where no press is allowed and attendees are told not to discuss what they hear, even Ho recanted his central tenant, and said, "Viremia [viral levels] are not predictive of clinical outcome."

"People can have a high viral load and be healthy and have a low viral load and be sick and everything in between," says Rasnick. "These guys will admit t his between themselves, they just don't admit it publicly."

Rasnick caught up with Cameron after his talk. He recounts the conversation. "He said they're 'living longer' during the era of protease inhibitors, but he said they 'look like hell.' He said they're wasting away and they just look like shit. I said, 'Is that because of the drugs?' And he said 'yes.'"

***

The AIDS magazine POZ and others like it are filled with protease inhibitor ads that drastically contrast with the cruel reality. The ads feature muscular, tanned, and beautiful people at the peak of their powers: climbing mountains, sprinting over hurdles, sailing, and generally beaming with life.

In reality, three years into the protease inhibitor craze, most people on cocktail therapy can barely function. I talked to one of the most well-known protease models, Michael Weathers, whose handsome face adorns several billboards across America, and he said that he had not only never taken protease inhibitors, but had never taken any AIDS drugs. He is perfectly healthy 13 years after learning he was positive. "They have this rule that they have to use HIV-positive models for their AIDS drug ads," Weathers comments, "but they certainly do not use models who are using their drugs. That would hardly make for effective advertising."

The list of side effects listed by the drug companies themselves in their own ads is so long it numbers in the hundreds. The toxic effects are so numerous, they have broken them down into categories. Within each of those body systems, up to 50 specific symptoms are listed.

For one of the drugs, Saquinavir, under "Adverse reactions," are listed: "intracranial hemorrhage leading to death" and "pancreatitis leading to death."

Leafing through POZ, I read the fine print that follows every protease ad. In each and every one, it states that the drugs have killed people. In the advertisement for the drugs.

Yet the accompanying text warns in parental tones about the importance of staying on the drugs no matter what.

Be smart, one ad for the Glaxo drug Combivir advises: Without your HIV drugs, there's nothing to stop the virus from making billions of copies of itself. Next time you're tempted to skip a dose or two, think again... HIV drugs should be taken on time, every day. That's the only way known to keep enough of each drug in your blood at all times to fight HIV.

How, I ask Joe Sonnabend, could all of this hype take place? How could David Ho be made Man of The Year? How could the eradication theory be extolled? How is it possible if David Ho's science is as bankrupt as all this?

Sonnabend pushes his glasses up onto his forehead and looks at me almost quizzically. Then he shrugs slightly.

"He had a really good publicist."

***

Ho's publicist was a man named David Corkery, from the PR firm Fenton Communications. "We took over to manage the cascade of publicity that ensued after he was made Man of The Year," says Corkery, flatly refusing to discuss the matter any further. "David Ho did not create all this," is all he will say, referring to the hype.

I set off in search of ground zero, a beginning, a place where the tornado started turning. I call people who work on the inside of the AIDS machine. They all speak -- angrily, but fearfully -- of a pharmaceutical industry that makes its presence felt to reporters, scientists, doctors, and AIDS activists. As Dr. Sonnabend put it, "The drug companies are present in some way in virtually every single moment of my professional career."

"It is absolutely extraordinary," says Dr. Miles, who says he has been on various drug companies blacklists for saying negative things about their products. "People don't realize all the myriad ways that doctors benefit from the drug companies.

"For example, let's say that drug company A likes the message that Dr. C is talking about, they can give a research grant to Dr. C and because it's listed as a 'research grant,' people will say, 'Oh well, this is above board,' when in fact it's nothing more than a glorified under-the-table payment.

"Now, let's say that you are Dr. C, and you have a $250,000 research grant from company A. What is the likelihood that you are going to say anything bad about their drugs? Zero. At best you are going to say nothing."

Miles has felt the heat of this situation personally, being one of the few mainstream AIDS doctors who stood up and resisted the hit-hard-hit-early mania.

"Just go to the U.S. Public Health Service web site. Under federal law they have to disclose who they have taken money from. It's right there. Some of these doctors have taken money from 15 to 20 different companies. If 20 companies that are in the business of making money for drug treatment are giving you money, can you honestly stand up and say, 'Don't treat!'"

Another man, who for years has worked on the inside of AIDS research, implores me not to print his name, swearing he will be out of a job immediately if I do.

"Look at the media, that's where it happens," he said. "Look at those earliest pieces about Ho and the cocktails that ran in the Wall Street Journal. They are just pure propaganda, pure drug company puff pieces.

"And those reporters won the Pulitzer that year for their AIDS reporting. The pharmaceutical industry exerts a huge influence on scientists and journalists.

"You have to understand that these AIDS journalists have very close relationships with the drug companies, with their PR people. That affects how things get reported. I mean, they fund everything. They fund all the research, first of all. There is almost no such thing as independent research. All clinical trials are paid for by the drug companies."

He laughs when I express alarm at this. "My God are you naive! Everybody -- not just David Ho -- the reporters, the doctors, everybody is part of this system. They're all part of the same club, and they all play the same game. They all have the same, big egos.

"And nobody -- certainly not the reporters -- is going to stand up and wave their finger and say, 'This is all a big horrible machine!' You know why? Because they're all profiting from it.

"Every year we go to these AIDS conferences, and all the professional AIDS-sters come in, all pumped up. And this is the moment where everybody gets blown. It's just gross.

"Look," he says, "if it were not for the profit motive, there would be no incentive for drug companies to make drugs. Drugs come from drug companies. They don't come from anywhere else. It's an industry, okay? It's just another industry."

Celia Farber has written on the issues and controversies surrounding HIV, AZT, and AIDS for more than a decade. She is a regular contributor to Esquire, Spin, USA Today, and Gear, among other U.S. publications. She is the mother of one son and resides with her family in New York City.