By Neville Hodgkinson
The Sunday Times (London) 4 April 1993
has been HIV-positive since 1984. He was diagnosed as having AIDS
in 1986. Today, seven years on, he says he feels fine with energy
levels that belie his 52 years. He does not take the anti-HIV drug
thousands of doctors and patients around the world, was neither
surprised nor disappointed last week when the Medical Research Council
announced that early treatment with AZT, sold under the brand name
Retrovir, is useless. In fact, he welcomed the announcement. Not
because he could tell his doctors "I told you so" he has
consistently refused entreaties to take the drug but because he
believes it is a poison that harms more than it helps, and can even
kill, producing symptoms which doctors misinterpret as AIDS.
He feels so
strongly about the issue that he works up to 18 hours a day establishing
a fledgling charity called Continuum, "an organisation for
long-term survivors of HIV and AIDS and people who want to be".
Founded late last year, the group already has 600 members.
nutritional and lifestyle approaches to combating AIDS, arguing
that these factors have been grossly neglected in the 10 years since
Dr Robert Gallo declared HIV to be the cause of AIDS.
To most within
the "AIDS" community, the MRC's announcement came as an
unpleasant shock. It meant that a decade of the most intensive research
ever mounted by the medical and scientific community against a single
virus, costing $1.5billion a year in the United States alone, had
left them empty-handed in therapeutic terms.
AZT, some doctors
had declared, was the "gold standard" of AIDS treatment.
They believed in it so strongly that many patients have come under
heavy pressure to take it, and to join trials liberally funded by
Wellcome, the drug's manufacturer. At the last count, more than
50 hospitals across Britain were involved in such studies. It is
even being given to HIV-positive children.
Yet as The
Sunday Times first reported in 1989, some scientists have argued
against the huge concentration of resources on AZT, and the wisdom
of giving patients a drug originally developed for cancer patients
but considered too toxic to administer.
They have also
questioned the rationale of an exclusively anti-viral approach to
AIDS, pointing out that science has not yet been able to locate
a mechanism through which HIV alone could account for the collapse
of the immune system seen in AIDS.
an Alice in Wonderland world," says Wells. "There are
so many uncertainties, and yet this extremely toxic drug has been
given to thousands of people, many of whom are completely well apart
from having antibodies in their blood to HIV. It is outrageous that
they should have been put at risk in this way."
Last week Wellcome
was trying to limit the damage to AZT's credibility, arguing the
trial results were not all they seemed, that several other trials
have shown benefit, and anyway, AZT's future lies in being used
in combination with other drugs. But the latest trial, called Concorde,
is far and away the most scientific mounted. Although it was directed
at finding out whether AZT would help symptom-free HIV-positive
patients rather than those with full-blown AIDS, it adds to the
concerns of scientists who doubt whether the drug has any place
in AIDS treatment.
AZT is big
business. It earned Wellcome more than Pounds 200m last year and
Pounds 131m in the six months to February this year. How could a
"useless" drug earn the reputation of being the "gold
standard" in AIDS and achieve such heights of success?
IN AN AGE when
so much has been achieved by science, both professionals and the
public often subscribe to the Spock-like image of the scientist
as a cool, calm, dispassionate seeker after truth. This is a myth.
Scientists are as prone as any other human beings to having their
judgement distorted by their emotions, whether from compassion or
greed. Normally, the scientific method seeks to overcome this subjectivity
by requiring careful analysis of claims.
In the mid-1980s,
American researchers were under huge pressure from a panic-stricken
homosexual community to fast-track anti-AIDS drugs on to the market.
AIDS conferences became as much political as scientific events,
with angry demonstrators chanting "Give us the drugs NOW!".
It was in such
a climate that AZT, first designed in the 1960s for the treatment
of leukaemia, came on the scene. The drug terminates DNA synthesis,
the process underlying cell division, and scientists originally
hoped it would prevent cancerous, rapidly multiplying blood cells
from replicating. It was abandoned because of its toxicity and ineffectiveness
After HIV was
declared the cause of AIDS by Gallo, Dr Samuel Broder, a colleague
at the US National Institutes of Health (NIH) in Bethesda, Washington,
instigated laboratory tests showing AZT helped block the virus's
replication. He steered the drug through regulatory procedures from
test-tube to patients in a record 19 months.
the time as associate director of the National Cancer Institute's
clinical oncology programme, Broder spoke in 1986 of the tension
he felt as his every move was scrutinised and criticised by AIDS
lobbyists. "I've had to recognise that we cannot approach this
problem in the usual scholarly way," he said.
Later he spoke
for much of the scientific community in declaring: "I view
AZT as the battle of El Alamein. It is symbolic that we can do something
against the virus that causes AIDS; that we can make progress; that
those who preached that it was inherently untreatable were wrong."
AZT was granted
its licence by America's Food and Drug Administration (FDA), with
licensing authorities around the world soon following suit, on the
basis of a single, multi-centre study. It took place in 1986, and
involved 281 AIDS patients. They were supposed to be tested for
24 weeks, but the trial was called off prematurely, when only 15
patients had run the full course, because there seemed to be a dramatic
improvement in survival in the AZT-treated group. Only one had died,
compared with 19 patients receiving a dummy pill.
Later, it became
evident that investigators and patients had not been "blind"
to who was receiving which pill; there were numerous breaches of
protocol designed to ensure comparability between the treated and
placebo-only patients, and sicker patients may have been placed
in the placebo group; there was an acceleration of deaths in the
treated group after the study ended (many had been kept alive by
repeated transfusions); many adverse reactions were not reported;
and that for 19 patients to die within weeks was a phenomenally
high death rate never seen again in any other comparable group,
suggesting they were not properly treated.
John Lauritsen, a gay movement activist and author of Poison by
Prescription: the AZT Story, FDA documents obtained under the Freedom
of Information Act show a meeting was convened to decide what to
do about the "protocol violations and bad data".
was made to keep everything," he says. "The researchers
excused these inexcusable decisions on two grounds: one, if they
didn't use the false data, there would be hardly any patients left
in the study. Two, using the false data didn't really change the
results very much." The FDA's stamp of approval on AZT set
in motion a bandwagon which seemed unstoppable.
A flood of
reports started appearing claiming various benefits for AZT. Many
of these were "anecdotal" that is, based on individual
clinicians' observations of patients, rather than arising from scientifically
sound trials. Lauritsen has a scathing description of such reports
in his book, published in 1990.
doctors," he writes, "many of them rather gullible individuals,
have been told that AZT represents the 'best hope'. With this expectation,
they begin dosing their patients with AZT, and sooner or later some
of them believe that they have 'seen good results'.
a patient, having undergone multiple transfusions and suffered agonising
side-effects, dies after 11 months; the doctor can then rationalise
that he would have died sooner if it hadn't been for the AZT."
poured into Wellcome's coffers from AZT, the company sponsored an
ever-growing number of research projects, as well as AIDS "educational"
materials and PR campaigns.
In August 1989,
Wellcome achieved a breakthrough that appeared to make the sky the
limit as far as its future earnings were concerned. It won "scientific"
backing for the idea that all HIV-positive patients, not just those
progressing towards AIDS, could benefit from AZT. A trial it had
sponsored with the National Institute of Allergy and Infectious
Diseases in the US also part of the National Institutes of Health
was stopped early, just like the original one, on grounds that the
drug had been shown to halve the rate at which a group of HIV-positive
patients became ill.
shares rose by 164p, adding Pounds 1.4 billion to the company's
stock-market value. And there were calls for a rethink over a multi-million-pound
Anglo-French study, known as the Concorde trial, which was tackling
the same question that the American study seemed to have answered:
of whether AZT could delay the onset of illness in all HIV-positive
people. Surely, with AZT now of proven benefit, it was unethical
to continue Concorde and deny some of its participants the benefits
offers lease of life", ran the headline across the front page
of The Independent on August 19, 1989, with the sub-heading "AZT
could be made widely available in Britain after US research shows
it can delay onset of the disease". Similar optimism was expressed
gave scientists involved with Concorde a tough decision to make.
They decided to compromise and keep the trial going, but change
the protocol so participants would no longer be left in the dark
on whether or not they were taking an active drug, but could, if
they wished, be switched to AZT.
still unanswered questions. It was possible AZT gave a short-term
boost to immunity, but failed to give benefit in the longer term.
The Americans' habit of stopping trials early could disguise such
There was also
evidence that the American trial, just like the original one with
AZT, had failed at least initially to conceal from doctors or patients
who was on the active drug and who was not, allowing bias to enter.
first results from the four-year Concorde trial were published in
The Lancet. They show no clinical benefit from AZT in symptom-free
HIV-infected individuals, either in terms of living longer or in
delaying progression towards disease. Armed with this exposure of
the weakness of previous claims, the licensing authorities must
surely now review whether AZT is fit to be prescribed to patients
with AIDS as well.
do so as a matter of urgency. Last year a four-year trial among
340 HIV-positive patients with preliminary signs of AIDS found that
rather than saving lives, AZT resulted in slightly more deaths.
trial appears to offer one crumb of comfort for Wellcome. Although
more than 100 of the 1750 patients in the trial had to drop out
because of severe side-effects, that is considered to be a relatively
low frequency, and no unexpected toxicity was seen.
however, believes the real picture is worse than it appears. The
reason, he says, is that most patients know from the changes in
their body when they are on AZT, even if supposedly "blinded"
to the fact when in a trial. He claims to know several who, not
wanting to rock the boat, have quietly taken unilateral action.
They have thrown their tablets down the toilet.
AIDS IS not
the first illness that doctors, en masse, have taken up as a crusade,
at the expense of science. Similar problems arose when the profession,
again egged on by drug companies, decided heart disease was caused
by raised blood pressure or raised cholesterol and tried to persuade
millions to change their eating habits or go on lifelong medication.
Numerous studies now show not only a lack of benefit from this approach,
but actual harm.
do bring benefit, but perhaps the worst feature of the medical and
scientific professions' behaviour on AIDS has been the enormous
dominance of a single focus HIV for research, prevention, and therapeutic
efforts, to the exclusion of other approaches.
Last week The
Lancet published a letter from Dr Gordon Stewart, professor emeritus
of public health at Glasgow University and a former World Health
Organisation adviser on AIDS, pointing out that previous AIDS projections
for 1992 were up to 10 times higher than the actual figure, largely
because of false assumptions about heterosexual spread.
been trying to put this across for nearly four years," Stewart
said. "I have tried numerous journals. The response has either
been rejection, or silence."
have included letters to several government bodies arguing that
the medical establishment had "jumped the gun" in using
AZT so widely. "I received no comment whatever in response,"
he said. "They were all persuaded HIV was the sole cause of
AIDS, that an anti-viral drug would destroy viral replication, and
thereby delay the onset of AIDS. They wouldn't consider any alternative
like its namesake, will also now break a sound barrier: the misguided
consensus on AIDS that has kept people like Stewart from being heard
for so long. *