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By Brian Deer
The Sunday Times (London) 1 Aug. 1993

AZT is death. Celia Farber picks up the pieces of a shattered medical establishment at the Ninth International Conference on AIDS in Berlin.

I emerged from the organized madness known as the Ninth International Conference on AIDS feeling strangely muted, a logjam of emotions caught in my throat: Despondency and rage among them, but also something bordering on joy, the joy of truth long held captive and finally released. The famous Concorde study has driven a stake through the heart of the seemingly endless AZT mythology that has enveloped and governed the AIDS treatment debate for six years now. It's baffling to see how truth can be suspended for long periods - endlessly subdued, rerouted, rejected. But like an airplane in a holding pattern, eventually it has to land.

In the past I have described my feeling that AIDS research is driven by ideological undercurrents - that it tends to mold all observations in such a way as to confirm, rather than challenge, its central believe system. A veteran attendee of these gigantic conferences, I have finally realized that simply to report the bits and pieces of data one has absorbed misses the point; it is not so much the data that changes from year to year, it's the AIDS establishment's response to and interpretation of the data. What reporters are really reporting on year is the zeitgeist of the establishment - which data they reject, endorse, ignore or trumpet. That is what shapes the forthcoming reality.

"Confusion," "reassessment," and "open-mindedness" were the buzzwords of this year's conference and normally arrogant AIDS figureheads gathered in roundtable discussions and spoke in hushed tones about the need to reexamine their old convictions about treatment, pathogenesis, and epidemiology. The reason for this remarkable soul-searching was that 1992-93 was a period that saw several cornerstones of AIDS ideology crumble.

Among them:

• That "early intervention" with AZT is in any way beneficial to people with HIV antibodies but no symptoms.

• That HIV causes the immune system to collapse by a direct cell-killing mechanism. (Instead, "indirect" mechanisms and cofactors were explored.)

• That CD4 cell counts are a good marker for immune status, health, or drug efficacy. Instead, it was revealed that large segments of the "healthy"-HIV-negative population have the same low CD4 counts typically associated with AIDS.

• That everybody with HIV will eventually succumb to AIDS and die. An estimated 5 percent of the HIV-infected population are now expected never to develop AIDS.

Last year, in Amsterdam, the great conference revelation was that an "AIDS-like illness" had occurred in people who showed no sign of infection with HIV. Health officials scrambled for plausible responses to the startling "mystery," which, in fact, had been documented in the medical literature since 1986. This year, in Berlin, the headline in the "news" that AZT, the pinnacle drug of AIDS treatment and research since 1987, is a failure.

To anybody who has followed the literature on AZT throughout, this is not news at all, but merely "official" confirmation of what has been known for years. If one had launched a full-scale truth-finding expedition - groping through the fallen rubble of AZT propaganda to find the kernel of truth underneath it all - the Anglo-French Concorde study would not have seemed revelatory at all.

Concorde went on for three years, examining 1,749 HIV-positive but healthy people at 38 health centers in the U.K., Ireland, and France. Because the research lasted the longest of all AZT studies to fate, and its pedigree was unassailable (it was conducted by the highly reputable British Medical Research Council and its French equivalent), Concorde could not be dismissed. The team concluded that AZT - a highly toxic and carcinogenic drug - neither prolongs life nor staves off symptoms of AIDS in people who are HIV-antibody positive but still healthy.

The blueprint for the Concorde "disappointment" has been in the literature for many years. As we reported in November 1989, the first objective study was completed in France in 1988 and was published with very little fanfare in the Lancet, a British medical journal. The study found that AZT was too toxic for most people to tolerate, had no lasting effect on HIV blood levels, and left the patients with fewer CD4 cells than they had started with.

If Concorde appeared surprising, it was because we in the U.S. have been captivated by self-induced AZT mythology for so many years. It was our FDA that approved AZT for use in 1987 based on very flimsy data and with a little arm-twisting, and it was our National institutes of Health (NIH) that expanded the parameters for AZT to be given to all healthy, HIV-positive people. In 1989, the NIH cited a study, known as Protocol 019, that it said had "clearly shown" that early administration of AZT would keep AIDS at bay in that population. Dr. Anthony Fauci, director of the National Institutes of Allergy and Infectious Diseases (NIAID), recommended that anyone with HIV antibodies and less than 500 CD4 cells should start taking AZT at once. At that time, that meant 650,000 people in the U.S.

I had heard that the Concorde team had been under tremendous pressure from AZT's manufacturer. Burroughs Wellcome, to soften its results. After one of the sessions in which the results were discussed, I walked up to Dr. Ian Weller, a chief investigator of Concorde, and congratulated him. I asked whether there had indeed been pressure from Wellcome. He nodded. A woman standing next to him, also on the Concorde team, nodded emphatically and finally burst out: "Yes, there has been pressure, and it has been placed at the very highest level."

Doesn't that, I asked, frustrate and infuriate you? She nodded, furiously, and said, "The most frustrating thing is that I can't tell you about it." Much of that raw Concorde data, particularly on toxicity, remains to be revealed.

Weller cleared his throat.

"We've carried out this study against incredible adversity, but we are not going to cave in to any pressure," he said. "We'll win the battle in the end. We show the science, that's all that matters."

...

I asked him how he felt about the fact that doctors in the U.S. still prescribe AZT to asymptomatics (people who have HIV antibodies but no symptoms of AIDS). "I think Concorde is going to take time to sink in," he said. "How you take on board the results very much depends on what you believe in before you saw them." As an afterthought he added, "I think it's very hard, if you've been giving AZT to large numbers of patients, to swallow this resultWellcome, the drug company that dominates AIDS research, is facing fierce criticism from doctors after it tried to overturn government-sponsored research. This found that AZT, the anti-AIDS drug, does not prevent the disease.

In a move without precedent since the drug appeared on the market six years ago, AIDS specialists have attacked the manufacturer. They have accused Wellcome researchers of misleading the scientific community following the publication of a report that appeared to show AZT was effective in AIDS prevention.

Leading doctors expressed outrage at what some regarded as a public relations stunt by Wellcome. The company's study, they said, was old, flawed in its methodology and had been terminated before anything meaningful could be reported. Their anger comes at a critical time for the company, which is seeking a licence to allow more widespread prescription of AZT. If successful, sales could be boosted by up to £ 2billion annually.

The article at the centre of the row was published on Thursday in an American medical journal. It was based on a study carried out for Wellcome in Australia and a number of European countries, mainly in the late 1980s.

According to the researchers, AZT halved the rate at which AIDS-related diseases developed; they urged extending the use of the drug to HIV-positive individuals who were otherwise healthy. If implemented, this would multiply by many times Wellcome's £ 250m market for the product.

The researchers' conclusions contradicted findings from the world's biggest study of the drug, conducted on behalf of the British and French governments and released four months ago. This, the "Concorde trial", found that AZT (or zidovudine) had no effect in preventing AIDS.

As The Sunday Times reported in May, Wellcome's financial dominance of AIDS science and treatment means it is seldom criticised by doctors or AIDS organisations. But this weekend Concorde researchers were the first specialists to break ranks over Wellcome's role.

Professor Ian Weller, of the Middlesex hospital in London, who was chairman of the Anglo-French study, said research of the sort published last week was aimed more at raising sales than knowledge. "Company trials are very much product-oriented," he said. "Government-sponsored studies are trying to answer bigger questions."

Weller whose previous academic post was sponsored by the Wellcome Trust, parent of the drug manufacturer said that if Concorde had not been supervised by government agencies he believed it would have been stopped at a point advantageous to AZT. This has occurred with all other tests of the drug.

Ann Marie Swart, a consultant at the Medical Research Council's HIV clinical trials centre in London, said AIDS specialists had seen and discounted the "new" research more than 18 months ago. "This paper is very misleading," she said. "It's a Wellcome trial. That's actually one of the problems."

The latest research was led by Professor David Cooper at St Vincent's hospital in Sydney and has been circulated by Wellcome since early last year. Cooper is a familiar face on the company-sponsored conference circuit and has been provided with media services by its public relations firm.

Cooper's work is helpful to the company because it supports an extension of the drug's vital European licence. This restricts AZT to patients with clear symptoms of AIDS. Although Britain and France are committed to these controls, Cooper has collaborators in five other Community countries which may now see it differently.

However, there is growing evidence that the tide is turning against AZT. In June a federal panel of experts in the United States, convened by the Food and Drug Administration, tightened advice on the drug's prescription. At its meeting, Cooper's paper was considered and its broad conclusions rejected.

Concorde counted 67 AIDS-related deaths among trial participants who took a placebo against 79 among those who took AZT. "There's been a huge change in the last year or so," said Weller, who believes doctors should ignore the company's claims.

"What we've seen as a result not only of Concorde, but of recent trials in the United States is that it's dawning on people that the drugs we have are not that useful." *