Dashed By Terrible Truth On AZT
Tim Rayment & Neville Hodgkinson
Sunday Times (London) 10 April 1994
IT WAS the
drug that held out hope to people carrying the world's most feared
virus. It had the power to move share prices by millions. What it
could not do was help people facing AIDS.
the truth about AZT is in the open: a comprehensive trial, so big
it equals all the other research put together, shows that the drug
which dominates AIDS treatment has no effect in delaying the onset
of the disease. After all the promise and the profits, AZT has nothing
to offer people with HIV.
came in the final report on the Anglo-French Concorde trial, published
yesterday in The Lancet. Some 1,749 patients with HIV, but who showed
no symptoms, were given either the drug or a placebo. There was
no statistical difference in the progress of the two groups: after
three years 18% had AIDS or were dead.
leave a terrible void for the 12m people worldwide said to be infected
with the virus, and crush any remaining hopes that AZT might delay
the onset of symptoms. They also raise questions as to how those
hopes were fuelled in the first place.
AZT were first revealed by The Sunday Times five years ago. A painstaking
investigation showed that AZT had been rushed to market on the back
of a flawed study that was supposed to demonstrate its effectiveness.
Food and Drug Administration (FDA), responsible for protecting the
public from risk, had been aware of flaws in the trial, but gave
AZT approval. Documents obtained under the American Freedom of Information
Act showed that records compiled during the trial had been altered,
giving the drug a more favourable record; "multiple deviations"
from the terms of the study had occurred; and FDA investigators
had argued for data from one centre to be dropped entirely from
the results. A senior FDA official believed AZT should not be granted
a licence, but was overruled.
did nothing to inhibit Wellcome, AZT's maker, from promoting its
drug. Patients with HIV, but without AIDS symptoms, were the new
target. They are worth more money because there are more of them
and because they have longer to live.
To show the
drug's usefulness to this lucrative group, Wellcome trumpeted a
big American trial called Protocol 019. The trial was halted in
August 1989, after less than two years, on the grounds that it had
already shown such benefit to HIV-positive people it would be unethical
not to give the drug to all who wanted it.
was judged only by time free from disease. A new analysis of the
trial data, however, reaches a similar conclusion to Concorde: that
AZT is essentially useless.
results were announced with a fanfare by the National Institute
of Allergy and Infectious Diseases, which sponsored it with Wellcome's
support. In London, The Independent newspaper gave its front page
to the findings, under the headline "AIDS drug offers lease
The very different
picture painted by last month's analysis, in the New England Journal
of Medicine, comes after investigators paid more attention to the
drug's side-effects. These can include anaemia, liver damage, fatigue,
nausea, headaches and sometimes a collapse in white blood cells,
making patients more prone to disease.
looked at the average time patients experienced neither a progression
of disease nor an adverse effect. Those treated with low doses of
AZT were found to suffer a reduction in quality of life "due
to severe side-effects of therapy" that approximately equalled
any benefit from slowing down the disease; people on higher doses
suffered even greater side-effects, outweighing the supposed benefit.
Dr Peter Duesberg,
the American virus expert who has claimed for years that AZT is
not a rational therapy, says it is clear that the original claims
were completely ill-founded. "The opposite interpretations
of the same data lead me to conclude that those responsible are
not acting as scientists; they are acting as politicians.
the time is ripe to say that AZT is detrimental, that it actually
hurts, the interpretation will change again."
with AIDS-related symptoms, AZT will continue to be prescribed:
the consensus remains that it gives a temporary benefit.
For those without
symptoms, hope centres on combinations of drugs, or on other approaches
such as gene therapy. However, Professor Ian Weller, of the Middlesex
hospital in London, who was the principal British investigator in
the Concorde trial, is alarmed by the drive to give AIDS patients
an AZT drug cocktail as if it were already an established therapy.
a suspicion of more toxicity if you combine it with other treatment,
and we are a long way from showing an important clinical benefit,
or that it is safer than AZT on its own," he said. "There
are physicians who are jumping the gun."
As late as
Thursday, Wellcome was insisting that AZT "remains the best
weapon we have to slow the progress of the disease". Dr Trevor
Jones, its research director, said: "The question is where
in the course of the disease you begin." *