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AZT: A Medicine from Hell October 1998
Praise of Folly Desiderius Erasmus (c. 1466
-1536), Dutch humanist.
In all the fuss about the minister’s decision on
AZT, no one, it seems, has stopped to ask, “So what the hell is this stuff
anyway?” In 1964, a chemist called Jerome Horwitz synthesised
a sophisticated experimental cell poison for the treatment of cancerous tumour
cells (1). It was called Suramin, or Compound S. Its formal title is
3’-azido-3’-deoxythymidine - zidovudine for short - but everyone knows it by
its nickname, AZT. It works like this. Thymidine is one of the four
nucleotides (building blocks) of DNA, the basic molecule of life. AZT is an
artificial fake, a dead ringer for thymidine. As a cell synthesises new DNA
while preparing to divide in order to spawn another, AZT either steals in to
take the place of the real thing, or else disrupts the delicate process by
interfering with the cell’s regulation of the relative concentrations of
nucleotide pools present during DNA synthesis. That’s the end of the cell line.
Cell division and replication, wrecked by the presence of the plastic imposter,
comes to a halt. Chemotherapeutic drugs such as AZT are described as DNA chain
terminators accordingly (2). Their effect is wholesale cell death of every
type, particularly the rapidly dividing cells of the immune system and those
lining our guts. Horwitz found that the sick immune cells went, but with so
many others that his poison was plainly useless as a medicine. It was akin to
napalm-bombing a school to kill some roof-rats. AZT was abandoned. It wasn’t
even patented. For two decades it collected dust, forgotten - until the advent
of the AIDS era. As soon as Dr Robert Gallo made his famous
announcement at a press conference on 23 April 1984 that his virus was the
probable cause of AIDS, the race was on to find a pharmaceutical weapon against
it. The stratospheric profit potential (since borne out) of being the first
past the post was on everybody’s mind. Obviously, if an already synthesised
drug could be applied to the malady, it would short-cut most of the road-race
there. AZT was fished off the shelf, along with numerous other abandoned brews,
and put to some in vitro tests. It
demonstrated a bright alchemical sparkle. On the basis of a reassuring but
fallacious assertion that AZT was specifically antagonistic to HIV, and a
thousand times more toxic to the latter than human cells generally, the drug
went to clinical trials. The chaos into which the trials degenerated is a tale
too long to tell here. It wouldn’t be extravagant to call them fraudulent (3).
(Subsequent trials consistently turned in opposite results.) At best, they were
so incompetently staged that the data gathered under them were useless, save to
note that one in five of its subjects taking AZT needed repeated blood
transfusions to keep going. Small surprise, since the label on bottles of AZT
supplied to laboratories bears a skull and cross-bones and cautions, “Toxic by
inhalation, in contact with skin and if swallowed. Target organ(s): Blood, bone
marrow…Wear suitable protective clothing.” Four months after the trials started, they were
called off prematurely, on an interpretation of provisional results deemed
positive for the drug by the trial overseer. Which is odd for a drug claimed to
be on double-blind test, with neither doctor nor patient supposed to know who
was on what, but there we are. Next, it went before the FDA, to be approved in
record time under huge political pressure from the gay lobby. Strong
reservations were expressed at the hearing about its dreadful toxicity. The
chairman’s vote against it was defeated. As the most poisonous drug ever licensed
by the FDA for indefinite use, and with the conviction apparently that the
terrible new disease needed a terrible medicine, AZT was approved for use in
extreme AIDS cases only - for which you might want to read, in cases of people
very ill with their presenting AIDS indicator disease, fungal pneumonia or what
have you. Scarcely a year later, in the orgy of stupidity that characterises
the AIDS age, AZT was officially recommended for administration to entirely
healthy people, whose misfortune it was to register positive to an HIV antibody
test. Since the drug destroys the very immune cells allegedly attacked by HIV,
the introduction of AZT as a treatment regimen for asymptomatic HIV-positive
people saw the AIDS mortality rate among the previously well take off like a
rocket. Five years and countless deaths later, and only after the disastrous
results of the European Concorde and St Mary trials, was this murderous
treatment recommendation reversed. AZT, it was found, did no good. Of course
not. On any intelligent consideration of its pharmacological action, AZT could
never be ‘antiviral’, any more so than arsenic could have cured the scurvy for
which it was administered to sailors, and later, to troops in the trenches in
the First World War. In Europe and the US, HIV-positive ‘long term
survivors’ quietly gather to form groups, having sloughed off the terror of the
death sentences imposed on them by their doctors. Here’s the strangest thing.
Without exception, what they find they all have in common is that they all
eschewed (or quickly gave up) AZT, related nucleoside analogues like 3TC, and
protease inhibitors. Some have pondered the unthinkable: that nearly all
medically managed AIDS cases, always terminal, represent that balefully
familiar phenomenon in the history of medicine, iatrogenocide - to be killed by
the cure. Their reasoning becomes less obscure when one reads the AZT package
insert. To do so might tempt one to wonder impertinently whether AZT isn’t AIDS
by prescription. Indeed, such perverse conjecture is actually confirmed in
capitals: AZT use “MAY BE ASSOCIATED WITH HEMATOLOGIC TOXICITY INCLUDING
GRANULOCYTOPENIA AND SEVERE ANEMIA” (destruction of white and red blood cells
respectively), and “PROLONGED USE OF RETROVIR HAS BEEN ASSOCIATED WITH SYMPTOMATIC
MYOPATHY (gross atrophy of muscle tissue) SIMILAR TO THAT PRODUCED BY HUMAN
IMMUNODEFICIENCY VIRUS”. As to the latter claim, history will judge whether the
thousands of healthy HIV-positive people who embarked on their metabolic poison
treatment and wasted away (just as the AZT insert predicted) would have died
had they ignored doctor’s orders and thrown their pills away. Here the syphilis
story is instructive. Before the introduction of mercury and arsenic salts
as a treatment for this clap, the organic brain damage and dementia that
signalled ‘tertiary-’ or ‘neuro-syphilis’ was quite unknown to medicine. When
penicillin replaced the older decoctions, it then disappeared. The moral is
hard to miss. One sane notion in that otherwise mad dance with death
that chemotherapy for cancer involves is that you stop before you drop. Since
healthy cells are always killed in the crossfire, the idea is to rescue the
patient from going over the cliff along with the target bad cells, by taking
him off the drug in the nick of time. That iron rule is broken in AIDS
treatment. You’re going to die, you’re told, so better take the bitter medicine
to the bitter end, to stave off the evil day. But as AZT heads like a
heat-seeking missile for one’s immune and energy transporting cells (“target
organs: blood, bone marrow”, remember?) dying of AIDS on AZT is a racing
certainty. No one has ever been cured by AZT, but it sells like hot cakes all
the same, still the most widely prescribed AIDS drug, and it reaps profits
counted in billions. Ever irrepressible as a medicine following one
failure after another, in 1994 AZT was proposed as a treatment for pregnant
women to prevent the transmission of HIV from mother to child, or so it was
touted. Until then, it had been staunchly contraindicated during pregnancy.
Generously underwritten by the drug’s manufacturer, the study, ACTG 076, in
which this startlingly novel use of AZT was tried, epitomises the junk-science
that characterises so much AIDS research. Of 477 babies born to HIV-positive
mothers in the trial, 13 in the AZT-treated group were born antibody-positive,
against 40 in the placebo group. Apart from the lunacy of basing a decision to
dose HIV-positive mothers with a cell-toxin as lethal as AZT on such feeble
numbers, the underlying assumption that an HIV-positive test result predicts
inevitable illness and death is a canard of modern medicine which,
surprisingly, wants for evidence. Most babies ‘seroconvert’ to HIV-negative in
any event, medicated or not. The other overarching myth is that the mere
presence of antibodies in one’s bloodstream signifies an active infection.
Isn’t it elementary that we carry antibodies to all sorts of pathogens that we
have met and defeated? Isn’t this first-year stuff? Advocates of AZT confess to
being completely in the dark to account for the vaunted HIV blocking effect
they claim. The reason why administering vitamin A instead works precisely the
same magic might be a pointer to something less interesting: stressed health,
thanks to chronic poor nourishment and living conditions. As for the positive
immune signals a ‘short course of AZT’ can generate, poison ingestion provokes
an immune reaction as the body rises to the insult. This is old hat. Thrown to the wind have been all the safeguards set
up to ensure that the Diethylstilbestrol and Thalidomide tragedies would never
happen again. Before the hysteria of the AIDS age, women were enjoined even to
avoid drinking beer during pregnancy. A recently reconfirmed active carcinogen,
and teratogen too - cells not killed outright are nastily maimed - AZT freely
crosses the placental barrier, so the package insert tells us cheerfully. Has
anyone here paused to question whether a growing foetus comprising rapidly
dividing cells should be exposed to a random terminator of DNA chain synthesis?
Apparently not. Certainly not the recipients of GlaxoWellcome’s largesse from
its slush fund of millions for those who make AIDS their business in this
country. Nor our doctors carrying out bold medical experiments on the foetuses
of pregnant black women - whose unlucky dice gives them a positive registration
to the irredeemably and hopelessly non-specific ‘HIV-antibody’ test. Of course
anyone in the game crying foul, and drawing attention to the reams of literature
in the medical journals about the harm caused by AZT, especially to the young,
is going to find himself sent off and defunded, for keeps. Were it not for the
amazing collapse of critical intelligence in the AIDS age, GlaxoWellcome’s
heart-warming contributions to ‘the fight against AIDS’, with its research
grants and cut-prices - described by the Mail
and Guardian as a “bouquet of assistance” - might have been seen less as
philanthropy than commerce, pure and simple. As it has achieved so successfully
abroad, what better way to fix its local market than by buying off our medical
establishment and ‘AIDS activist’ crowd with lolly aplenty to fund their dumb
projects? And by enticing our government with current discounts for its rancid
wares, in order to hook longer-term contractual commitments. The AIDS Law Project at Wits currently busies itself
with plans to sue the minister in the High Court for an order compelling her to
respect ‘pregnant women’s rights to AZT’, and dole it out on the house. Then
again, its ‘AIDS activist’ lawyers gratefully take junkets to AIDS conferences
in holiday cities overseas at GlaxoWellcome’s expense. The ‘human rights’ they
pursue might be better served were these legal crusaders to call off their
foolish case and think of ways best to bite the hand that feeds them. Several
actions for loss of support have been launched against GlaxoWellcome in England
and the USA, arising out of the deaths of family members killed by their
doctors’ prescriptions of AZT (5). Although she has justified her perplexing decision
on AZT on the basis of financial considerations exclusively, saying she would
rather spend her money on ‘AIDS education’, one day Health Minister Nkosazana
Zuma will be praised for her great prescient wisdom in keeping AZT away from
pregnant women and their foetuses. A bit like much-lauded Dr Francis Kelsey,
whom Kennedy honoured for her wise perspicacity in sparing the USA the European
Thalidomide calamity, when in truth her only notable trait was her fortuitously
inefficient foot-dragging in obstructing the start of the FDA approval process. It’s high time that everyone involved in this
nightmarish mess went off to do some basic homework in the subject in which
they have so much to say for themselves. (1) Horwitz, J.P.,
Chua, J. and Noel, M: Nucleosides. V. The
monomesylates of 1-(2’-Deoxy-beta-D-lyxofuranosyl)thymine, Journal of Organic Chemistry 29:
2076-2078 (1964). However, an American biochemistry professor with whom I have
corresponded privately makes a documented prior claim to the first synthesis of
AZT in the autumn of 1961. He prefers both to remain anonymous and not to upset
the settled history - based on the first to publish. He mentioned to me that he
employed AZT as an experimental cell-poison against leukaemic blood cells, and
against the bacteria Salmonella Potsdam
and E. coli. (Studies in the ‘90’s
have confirmed AZT’s activity against all three.) He pointed out that after
publishing his paper, Horwitz investigated the activity of AZT against Jensen
tumour cells, and not against leukaemic blood cells as I reported originally in
line with the conventional history. He also criticised my repetition of the
claim that Horwitz abandoned AZT because of its toxicity (see for example the
excerpt from Radford’s article immediately below). He said the reason was its
inactivity against target cancer cells, while the acute toxicity of AZT emerged
only later. Actually, Horwitz has made contradictory statements about this.
Reviewing this essay, he remarked, “…you are justified in sounding a warning
against the long-term therapeutic use of AZT, or its use in pregnant women,
because of its demonstrated toxicity and side effects. Unfortunately, the
devastating effects of AZT emerged only after the final level of experiments
were well underway, that is, the experiments which consisted of giving AZT to
large numbers of human patients over a long period of time. Your effort is a
worthy one… I hope you succeed in convincing your government not to make AZT
available...” In an enthusiastic article
about the pharmaceutical industry in the UK, Tim Radford wrote in the Guardian on 30 March 2000, “They settled
on an anti-cancer drug which had proved too toxic to use against cancer: It was
AZT… Since DNA is a ubiquitous part of life, compounds that act against it can
potentially stop life forms like bacteria, like viruses, like humans. Of
course, they can cause cancer as well, so balancing the risks is an essential
part of the fascination.” The fascinating risks for the development of cancer
posed by the administration of AZT are examined extensively in my reply to Dr
Martin, AZT and Heavenly Remedies.
(2) DNA chain formation
termination - described in this paragraph - is generally understood to be the
basic pharmacological action of AZT. GlaxoWellcome asserts in its PRODUCT
INFORMATION release about AZT, “In vitro,
zidovudine triphosphate has been shown to be incorporated into growing chains
of DNA by viral reverse transcriptase. When incorporation by the viral enzyme
occurs, the DNA chain is terminated.” In a glitzy CD dished out at the 13th
International AIDS Conference in Durban, GlaxoWellcome claims similarly:
“Nucleoside Reverse Transcriptase Inhibitors – NRTIs – [like AZT are]
phosphorylated by cellular enzymes… competitively inhibit viral DNA synthesis
[and are incorporated] into the DNA thus terminating DNA synthesis.” This conventional model of
AZT pharmaco-kinetics is accepted by a vociferous critic of the drug, Dr Peter
Duesberg, professor of molecular biology at the University of California at
Berkeley. His criticisms go principally to the unacceptable toxicology profile
of AZT, and do not take issue with its manufacturer’s claims about its mode of
action. Accordingly, in Inventing the AIDS Virus he writes,
“While on AZT, Bergalis once told a reporter she hoped to also get
dideoxyinosine (ddI), another experimental AIDS drug. This drug and ddC, two
products of cancer chemotherapy research, work in precisely the same way as
AZT. Chemically altered building blocks of DNA, they enter the growing chain of
DNA while a cell is preparing to divide and abort the process by preventing new
DNA building blocks from adding on… So, like AZT, ddI and ddC kill dividing
cells and have similar toxic effects. They destroy white blood cells and
therefore can cause AIDS.” Jay Levy, professor of medicine and director of the
Laboratory for Tumor and AIDS Virus Research at UCSF (and unlike Duesberg, a
vocal protagonist of the orthodox HIV-AIDS model) said in Newsday on 12 June 1990, “AZT can only hasten the demise of the
individual. It’s an immune disease and AZT only further harms an already
decimated immune system.” Duesberg’s most recent and most detailed critique of
AZT, co-authored with pharmacology biochemist David Rasnick Phd, is contained
in The AIDS Dilemma: Drug diseases blamed
on a passenger virus, published in Genetica
in mid-1998. It can be read on the internet. As Mycek et al put it in their text Pharmacology (2nd ed), it is
trite that before the drug can be incorporated into DNA, “AZT must be converted
to the corresponding nucleoside triphosphate by mammalian thymidine kinase in
order for it to exert its antiviral activity.” Recognising this, GlaxoWellcome
claims, “Within cells, zidovudine is converted to the active metabolite,
zidovudine 5’triphosphate (AztTP), by the sequential action of cellular
enzymes.” But numerous investigations since AZT was approved by the FDA in the
US have found that AZT is triphosphorylated in
vivo very inefficiently, and at least one order of magnitude lower than
necessary for its claimed anti-HIV effect. Consequently viral DNA chain
termination by the incorporation of metabolically altered AZT into DNA in place
of natural thymidine is insignificant in relation to other activities of the
drug, inter alia as a potent oxidising
agent. This subject will get a close look in my reply to Dr Martin, AZT and Heavenly Remedies. AZT also
disrupts cell division by perturbing the relative levels of natural nucleotide
pools, with the drug acting as a ‘sink’ and sponging up phosphate molecules
essential to the process. Starved of these molecules and denied the energy they
provide, dividing cells die. This pivotal criticism of
the conventional model of the pharmacology of AZT - namely that AZT is not in
fact triphosphorylated as GlaxoWellcome claims it is - is made and elaborated
extensively in a paper discussed in my reply to Dr Martin, A Critical Analysis of AZT and its Use in AIDS by
Papadopulos-Eleopulos et al,
published in mid-1999 as a special supplement to the academic medical journal Current Medical Research and Opinion.
Like Duesberg and Rasnick’s paper mentioned above, it is archived on the
website www.virusmyth.com . Librapharm
also has it posted at: http://www.librapharm.co.uk/cmro/vol_15/supplement/main.htm (3) The way in which AZT was
approved and reached the market as an AIDS drug has been closely researched and
reported by John Lauritsen (Poison by
Prescription: The AZT Story, and The
AIDS War), Celia Farber (Sins of
Omission, The AZT Scandal), Bruce Nussbaum (Good Intentions), Elinor Burkett (The Gravest Show on Earth), Peter Duesberg (‘With therapies like these who needs disease’ in Inventing the AIDS Virus) Martin Walker (Dirty Medicine and HIV, AZT,
Big Science & Clinical Failure) and Steven Epstein (Impure Science: AIDS, Activism, and the
Politics of Knowledge). It’s an amazing story, and is certain to haunt
GlaxoWellcome in litigation sooner or later. Some of this writing can be read
on the website mentioned above. (4) In his address to the
National Council of Ministers on 28 October 1999, during which he ordered an
investigation into the safety of AZT, President Mbeki mentioned these lawsuits.
GlaxoWellcome’s representatives in South Africa immediately denied them. A few
days later, the President’s office asked me for details. I referred to the
English cases of Threakall and others, and the American Nagel and McDonnell
cases, all of which had been reported in the press. A month later however, in a
telephone call from Susan Threakall’s English solicitor Graham Ross, I was
informed that her action, his lead case, had been withdrawn a couple of months
earlier. In March 2000, Paul Headlund, the American attorney who had handled
the Nagel and McDonnel cases, told me that the claims had not been pursued.
GlaxoWellcome was therefore technically correct in disputing Mbeki’s statement
that there were cases concerning AZT pending against it at that time. What GlaxoWellcome
omitted to mention was that a month earlier a court in Maine in the US had
dismissed a bid by health authorities to compel Valerie Emerson to administer
AZT to her son after her daughter had died on the drug, and held, “She feels
that she has willingly and in good faith surrendered up the life of one child
to the best treatment medicine has to offer and does not want to do the same
with the next. Nikolas has made significant strides recently in gaining weight
and overcoming developmental deficits, and appears happy and healthy. She does
not want to see this child take on the pallor and pain of a sick and dying
child.” I am currently briefed in a claim against GlaxoWellcome for the widow and minor son of an attorney killed by a single month’s course of AZT and 3TC treatment. The action will be the first world-wide in which the integrity of GlaxoWellcome’s claims about the molecular pharmacology of AZT and the adequacy of the information provided about its hazards will be examined by a trial court in the light of the Papadopulos-Eleopulos et al review paper and others canvassed in my reply to Dr Martin. It will be the plaintiffs’ case that AZT is an unreasonably dangerous drug with no therapeutic or palliative value as an ‘antiretroviral’ whatsoever. This action is my lead case. I have since been instructed to represent two other plaintiffs, one who suffered permanent leg muscle damage and another liver damage after treatment with the drug. For another action I am handling involving AZT poisoning, but brought on a different basis, see An AIDS Case in the appendices to this debate. * AZT:
A Medicine from Heaven THE Southern African HIV/AIDS
Clinicians Society responds to an article AZT: A Medicine from Hell, by Anthony
Brink, published in The Citizen on March 17. Human Immunodeficiency Virus (HIV) disease is a major global health
problem and is associated with a significant morbidity and mortality. The number of people infected with HIV is rapidly increasing; recent
estimates indicate more than 30 million adults and 1,1 million children are
infected worldwide. In South Africa it
is estimated that in excess of three million people are infected. It has been predicted that 40 million
persons, including four to five million children, will have acquired the
infection by the year 2000.
Mother-to-child transmission, the major cause of HIV infection in
infants, has led to a 30 percent increase in the mortality rate of infants and
children in recent years. The introduction of highly active anti-retroviral therapy (HAART) has
been good news. In the US the
age-adjusted death rate among people with HIV in 1997 was less than 40 percent
of what it was in 1995. This
experienced was mirrored in other Western nations where dramatic declines in
morbidity and mortality as a result of the increasing use of combination
anti-retroviral therapy has occurred; many of these regimens contain AZT. When AZT and other nucleoside analogues were first introduced they were
used as monotherapy (a single drug was used).
Clinical experience quickly showed that the effect of a single drug was
short-lived, as resistance to the drug developed. It was then shown that by using a combination of drugs, a more
lasting effect was obtained. BENEFICIAL An added advantage of combination therapy was that the drugs acted at
different stages of the replication cycle of the virus. This option therefore made sense; the risk
of drug resistance was drastically reduced and long-lasting beneficial effects
have been recorded. AZT together with
3TC and a protease inhibitor is a combination that has been found to be highly
effective. Impaired quality of life associated with the progression of HIV disease
has a profound effect on the patient and leads to an increase in the direct
medical and non-medical costs of illness. Published studies have shown that
patients on combination therapy with AZT and 3TC have been able to maintain or
more importantly improve their quality of life. So effective are combination anti-retroviral regimens in reducing the
complications of the disease that there are anecdotal reports emanating from
the US that Aids wards are being emptied of their patients and in some
instances wards have been closed.
Clinicians are now treating patients in out-patient settings and the
status of the disease has changed to that of a chronic manageable disease. It is however, in the arena of prevention of HIV infection that AZT has
produced dramatic results. Worldwide, approximately 500 000 infants become infected each year as a
result of mother-to-child transmission.
In some African countries 25 percent of pregnant women are infected with
HIV. Without preventative therapy up to
a third of their babies may become infected; many of these children will die in
their early years. In 1994 a clinical trial conducted in the US and France (ACTG 076)
demonstrated that AZT given to mothers during their pregnancies, intravenously
during labour and orally to their babies for six weeks reduced the risk of
mother-to-child transmission by 67 percent.
This regimen has been adopted as the "standard of care" in the
US. However, it is unsuitable for developing countries because of its
complexity and cost. To address the problem the Ministry of Health in Thailand introduced a
trial of simpler and less expensive regimens of AZT to prevent mother-to-child
transmission. This trial showed that a
simpler regimen of AZT given orally to mothers in the last weeks of pregnancy
reduced the risk of transmission by 50 percent. This short course AZT regimen (so-called Thailand regimen) is
much more suitable for developing countries than the US-protocol because it is
much easier to administer and less costly ($50 v $800). Preliminary data from United Nation Aids Programme (UNAids)- sponsored
studies have also demonstrated that even more abbreviated, affordable,
AZT-containing regimens may be equally effective. Another instance where preventative AZT therapy is commonly used is in
the event of a health-care worker (HCW) sustaining an occupational exposure to
blood or body fluids from an HIV infected person (eg. needle-stick injury). These occurrences are usually charged with much emotion and HCW’s are,
quite justifiably, entitled to appropriate post-exposure prophylaxis to be
commenced as soon as possible after the injury. A multinational study conducted among occupationally exposed
HCW’s demonstrated a 79 percent reduction in the risk of acquiring HIV
infection when AZT was used as post-exposure prophylaxis. TOXICITY The toxicity of AZT is a very real issue however, the toxicity
(particularly bone marrow toxicity) is usually noted in patients with advanced
HIV disease whose bone marrow function may already be impaired by HIV
disease. Toxicity does not appear to be
a problem during short-term use (post exposure prophylaxis or mother-to-child
transmission prevention). Nevertheless vigilance and monitoring on the part of the clinician is
necessary. If toxicity occurs the drug
should be stopped and other drugs substituted and any appropriate management
should occur. Toxicity in most cases is
reversible. In addition, careful monitoring of babies whose mothers took AZT
during pregnancy has failed to show any significant abnormal findings. Thus AZT in combination with other drugs has proved to be invaluable
for the treatment of those already infected with HIV and has also proved to be
a potent preventative agent in the mother-to-child setting and for occupational
exposures. For these very reasons the
drug AZT deserves the accolade: AZT: a medicine from heaven. Desmond J Martin is president
of the Southern African HIV/Aids Clinicians Society. Note: Dr Martin has no
conflict of interest and has not received financial sponsorship from
GlaxoWellcome. * AZT and
Heavenly Remedies What can you do against the lunatic...who gives your arguments a fair
hearing and then simply persists in his lunacy? Winston Smith, in Nineteen Eighty-Four George Orwell [1] AZT - pure
poison? Nonsense, retorts Dr Martin, with the avuncular bedside reassurance of
doctor who knows best. AZT, he proclaims, is God’s own medicine. [2] In his
letter covering his response to my essay AZT:
A Medicine from Hell, Martin rebukes the editor of the Citizen for his “gross irresponsibility” in publishing my piece
without having first obtained the views of “the established experts.” In this
reply, we’ll have a look at what experts from the top drawer of the AIDS
research establishment have to say about AZT, the kind of guys who get to
publish in the world’s most splendid medical and scientific journals. [3] The first
clinical report from practising doctors that something was terribly wrong with
Dr Martin’s Heavenly Medicine was filed by Dr Laura Bessen and her colleagues
in March 1988. In a letter to the New
England Journal of Medicine headed Severe
Polymyositis-like Syndrome Associated with Zidovudine Therapy of AIDS and ARC,
they reported, “All patients had an insidious onset of myalgias, muscle
tenderness, weakness, and severe muscle atrophy favouring the proximal muscle
groups. Physical examinations revealed varying degrees of muscle weakness and
grossly apparent atrophy. Weight loss due to muscle loss was uniformly noted;
in one patient, the loss was a striking 18kg.” Bessen et al noted, “We did not observe this illness before zidovudine was
available…” It sure wasn’t the HIV, because fortunately for the patients they
were treating, the doctors found that “the syndrome was ameliorated after the
drug was stopped.” But the patient doesn’t always recover: In their review
paper Mitochondrial toxicity of antiviral
drugs in Nature Medicine in 1995,
Lewis and Dalakis noted, “In some cases, reversal of symptoms corresponds to
cessation of therapy; in others toxicity persists…” They also drew the
important distinction: “It is self-evident that ANAs [antiviral necleoside
analogues] like all drugs have side-effects. However the prevalent and at times
serious ANA mitochondrial toxic side-effects are particularly broad ranging…” [4] Two
months after Bessen’s letter, Gorard et
al reported their observation of Necrotising
myopathy and zidovudine in the Lancet:
“A 24-year-old woman presented in January 1988 with a 2-week history of
progressive leg weakness and difficulty in walking. She had been found to be
HIV antibody positive in April 1986, and in October 1986, Pneumocystis carinii
pneumonia developed. After the pneumonia she had been on zidovudine 200 mg
4-hourly and had required three blood transfusions for consequent
myelosuppression [white blood cell depletion]. On examination there was
proximal weakness but no wasting of the upper and lower limbs, tenderness of
the shoulders and thighs, and preserved deep tendon reflexes. Her gait was
waddling and she was unable to rise out of a chair without using her arms...7
days after zidovudine withdrawal, her proximal weakness and muscle tenderness
had improved significantly, and muscle force was clinically normal at follow-up
2 months later.” In September in the same journal, Helbert et al published their findings on Zidovudine-associated myopathy: “A severe proximal myopathy,
predominantly affecting the legs, seems to be a significant complication of
long-term zidovudine therapy, even at reduced doses; it affected 18% of our
patients who had received treatment for more than 200 days. Other drugs could
not be implicated. The pathogenesis is obscure; the myopathy resolves on
cessation of zidovudine, but not on dose-reduction…” For some people anyway.
After just a month’s course of AZT treatment, a colleague of mine lost most of
his muscle mass and died several months later weighing 42kg. A client has
suffered permanent leg muscle damage and can no longer walk more than short
distances without experiencing the fall-down fatigue of a marathon runner at
the end of his race. [5] Bessen,
Gorard, Helbert and their colleagues’ clinical observations were investigated
and reported by Dalakas et al in 1990
in the New England Journal of Medicine.
Comparing the myopathy caused by AZT with that presumed to be caused by HIV,
they concluded that “long-term therapy with zidovudine can cause a toxic
mitochondrial myopathy, which...is indistinguishable from the myopathy
associated with primary HIV infection... Before 1986, when zidovudine (formerly
called azidothymidine) was introduced, the number of patients with
HIV-associated myopathy was small, and myopathy was considered a rare
complication of HIV infection. During the past two years, an increasing number
of patients receiving long-term zidovudine therapy have had myopathic symptoms
such as myalgia (in up to 8 percent of patients), elevated serum creatine
kinase levels (in up to 15 percent), and muscle weakness. These symptoms
generally improve when zidovudine is discontinued.” In 1994, Dalakas et al elaborated on this in their paper
in Annals of Neurology with the title
summing it up, Zidovudine-Induced
Mitochondrial Myopathy is Associated with Muscle Carnitine Deficiency and Lipid
Storage: “The use of zidovudine (AZT) for the treatment of acquired
immunodeficiency syndrome (AIDS) induces a DNA-depleting mitochondrial
myopathy, which is histologically characterized by the presence of muscle
fibres with ‘ragged-red’-like features, red-rimmed or empty cracks, granular
deterioration, and rods (AZT fibres)… We conclude that the muscle mitochondrial
impairment caused by AZT results in (1) accumulation of lipid within the muscle
fibres owing to poor utilization of long-chain fatty acids, (2) reduction of
muscle carnitine uptake by the muscles, and (3) depletion of energy stores
within the muscle fibres.” In Clinical
Pharmacology (1997, 8th ed.) Laurence, Bennet, and Brown say about AZT, “A
toxic myopathy (not distinguishable from HIV-associated myopathy) may develop
with long term use.” In fact whether muscle wasting ever occurs among
HIV-positives who avoid AZT and related drugs is doubtful: Coker et al mentioned in AIDS in 1991 that “A clinically significant myopathy that precedes
the development of zidovudine associated mitochondrial myopathy has been a
rarity in our experience.” In February 1999, in Neurotoxicology,
Waclawik et al published their
investigation of whether the direct muscle cell toxicity of AZT is aggravated
by retroviral infection. And found in the negative, as the conclusion in the
title tells: Zidovudine [AZT]
myotoxicity: quantitative separation of AZT effects on proliferation and
differentiation of muscle cells in vitro. Lack of myotoxicity potentiation by
retrovirus. [6] Till et al reported their investigation of AZT-muscle
damage in Annals of Internal Medicine
in 1990 under the pointed title Myopathy
with Human Immunodeficiency Virus type 1 (HIV-1) infection: HIV-1 or
zidovudine?: “Results of quadriceps muscle biopsies done on our patients
who responded to zidodvudine withdrawal showed severe myopathic changes without
evidence of inflammatory infiltrates. Electron microscopy revealed many
ultrastructural changes, including destruction of the sarcomere profile with
z-band change in the form of streaming and rod bodies. Muscle mitochondria
showed wide variation in size, swelling, degeneration and laminar bodies…There
have been 40 case reports of patients who have developed while taking
zidovudine (including our 5 symptomatic patients). Zidovudine therapy was
discontinued in 34 of these patients and 26 improved.” Arnardo et al reported their comparison of
muscle biopsies from HIV-positive patients treated with AZT and those who had
not in the Lancet in 1991. In the AZT
exposed tissues they observed “inflammatory myopathy with abundant ragged-red
fibres (RRF)… No abnormal mitochondria were noted histologically in samples
from the HIV-positive patients who had not received zidovudine.” Pezeshkpour et al reported a similar comparison in Human Pathology in the same year, “…muscle
biopsy specimens from [HIV-positive] patients show a variety of features,
including phagocytosis, degeneration or necrosis of muscle fibres, endomysial
or perimysial inflammation, cytoplasmic bodies, and nemaline (rod) bodies.
Following the introduction of zidovudine (AZT) for the treatment of the
acquired immunodeficiency syndrome (AIDS), the number of HIV-positive patients
with myopathic symptoms has increased. Zidovudine has been implicated as the
cause of the myopathy because these symptoms generally improve when AZT is
discontinued.” Upon a comparative analysis they found “specific structural
changes [to muscle tissue] associated only with AZT, but not with HIV [and
that] mitochondrial abnormalities are unique to AZT-treated patients. Since
mitochondrial DNA is specifically reduced, the structural changes [to
AZT-exposed muscle tissue] noted on electron microscopy are probably associated
with mitochondrial dysfunction. Zidovudine, a DNA chain terminator that
inhibits the mitochondrial y-DNA polymerase is toxic to muscle mitochondria.”
Any doubts were settled by Mhiri et al
in Annals of Neurology, also in 1991.
Their comparative study “identified a distinct clinicopathological picture of
zidovudine-induced myopathy associated with mitochondrial dysfunction”, hence
the title: Zidovudine Myopathy: A
Distinctive Disorder Associated with Mitochondrial Dysfunction. [7] In their paper Massive Conversion Of Guanosine To 8-Hydroxy-Guanosine In Mouse Liver
Mitochondrial DNA By Administration Of Azidothymidine published in Biochemical and Biophysical Research
Communications in 1991, Hayakawa et
al confirmed, “Recently, acquired mitochondrial myopathy caused by AZT
therapy in patients with AIDS was reported: typical ragged red fibres and
paracrystalline inclusions in mitochondria were seen in biopsied muscle
specimens from such patients. As there is ample evidence indicating that
mitochondrial myopathy is phenotypic expression of mutant mtDNA, the authors
intended to establish an animal model of the disease as well as to elucidate
the mechanism of mtDNA mutation by examining mouse liver mtDNA after
administration of AZT.” They found that “oral administration… for four weeks
converted dG [deoxyguanosine, another nucleotide, i.e basic building block of
DNA] in liver mtDNA [mitochondrial DNA] hydrolysate massively to 8-OH-dG [the
oxidised, destroyed form of the DNA nucleotide]. Even below 1/10th
the dose given to patients (AZT 1mg/kg/day) 25.2% of the total dG was converted
to be 8-OH-dG. 38.1% of the total dG
was converted to 8-OH-dG by AZT, 5mg /kg/day [half the human equivalent dose].
…This suggests that orally administered AZT interrupts mtDNA replication.
Another possible cause is that mis-terminated mtDNA would result in impaired
mitochondrial inner membrane, leading to production of OH which induces
formation of a DNA-protein cross-link involving cytosine and tyrosine. Such
cross-link disturbs the extraction of mtDNA resulting in its low recovery from
mitochondria… Recently it was reported that a single 8-OH-guanine residue
inserted in a viral genome induced a G.A mispair during replication leading to
the G.C to T.A transversion mutation, reflecting structural and conformational
changes imposed by the adducted purine within the DNA helix. MtDNA exists in
the matrix of mitochondria, so that the leak of oxygen radicals from impaired
respiratory chain with AZT attacks guanine residue converting to 8-OH-guanine,
leading to further mtDNA mutation. There is a general consensus that
mitochondria are less efficient in repairing DNA damage and replication errors
than the nucleus. For example they lack excision repair and recombinational
repair mechanisms. The higher steady state of oxidative damage in mtDNA than in
nuclear DNA is most likely due to a copious flux of oxygen radicals,
inefficient repair, and the nakedness of mtDNA. Thus oxidative damage of mtDNA
can be accumulated during even short periods of AZT administration. Several
point mutations found in mtDNA of patients with mitochondrial myopathy could be
originated from the oxygen damage of mtDNA. Conformational changes in the DNA
helix by the adducted purine would promote deletion of mtDNA which is common in
degenerative neuro-muscular diseases. The animal model of mitochondrial
myopathy with AZT administration reported here seems to be useful for
elucidating the mechanism of mtDNA mutations leading to myopathy. However, for
AIDS patients, it is urgently necessary to develop a remedy substituting this
toxic substance, AZT.” In 1991, in Neuromuscular
Disorders, Chariot and Gherardi published a supporting paper Partial Cytochrome c Oxidase Deficiency and
Cytoplasmic Bodies in Patients with Zidovudine Myopathy, “Long term therapy
with [AZT] can induce a toxic myopathy associated with mitochondrial changes.”
Most recently, in their paper Zidovudine-induced
experimental myopathy: dual mechanism of mitochondrial damage in the Journal of Neurological Science in July
1999, Masini et al “investigated the
in vivo effect of AZT in an animal model species (rat) not susceptible to HIV
infection. Histochemical and electron microscopic analyses demonstrated that,
under the experimental conditions used, the in vivo treatment with AZT does not
cause in skeletal muscle true dystrophic lesions, but rather mitochondrial
alterations confined to the fast fibers. In the same animal models, the
biochemical analysis confirmed that mitochondria are the target of AZT toxicity
in muscles” particularly “mitochondria energy transducing mechanisms.” Do you
think the manufacturer paid any heed to any of this? With all that money
rolling in, you must be joking. [8] The
burden of these reports is plain: AZT rots your muscles. As it does so, the
patient enjoys Martin’s “quality of life” while he inexorably slips away with
the wasted appearance of a concentration-camp victim. Compounding this is the
fact that at the same time that his muscle tissue is being poisoned and is
dying off, the patient literally starves to death, thanks to the decimation of
the cells that line his gut walls. This hampers the digestion of what food is
retained in the gut following intense biliousness and diarrhoea after AZT
ingestion. (A client of mine reported, “The worst experience of my life.”)
Throw a protease inhibitor into the ‘cocktail’, and protein digestion is fouled
into the bargain, by inhibiting cathpepsin, an essential digestion enzyme. When
the patient dies, as he inevitably must, the image of the gaunt white AIDS
patient who horribly and mysteriously wastes away is reinforced in the popular
consciousness. Another AIDS case for the statistical tally. And to add to the
quilt. Of course nobody cared much
about disease-caused wasting in Africa, commonplace from time immemorial where
poverty-linked tuberculosis, malaria and gut illnesses are endemic, until its
opportunities for research grants popped up when this wasting was renamed ‘slim
disease’ or AIDS. In the AIDS age, rural poor don’t die of the privations of
poverty any more, they die of promiscuity. The ‘AIDS experts’ shift the cause
of disease from outside to inside. How convenient in the age of the ‘global
economy’. [9] How rapid a poison is AZT? Some people last a
couple of years. On the other hand my colleague was killed by a single month’s
course of AZT (stretched over two because he found it so unbearable). This is
no mystery in the light of numerous investigations of how quickly the poison
sets in. In February 1999, in Free
Radical Biological Medicine, Szabados et
al looked at the Role of reactive
oxygen species and poly-ADP-ribose polymerase in the development of AZT-induced
cardiomyopathy in rats: “The
short term cardiac side-effects of AZT (3'-azido-3'-deoxythymidine, zidovudine)
was studied in rats to understand the biochemical events contributing to the
development of AZT-induced cardiomyopathy. Developing rats were treated with
AZT (50 mg/kg/day) for 2 wk and the structural and functional changes were
monitored in the cardiac muscle. AZT treatment provoked a surprisingly fast
appearance of cardiac malfunctions…” In 1991 in Laboratory Investigations, Lamperth et al reported Abnormal
skeletal and cardiac muscle mitochondria induced by zidovudine (AZT) in human
muscle in vitro and in an animal model within three weeks of experimental
exposure to “AZT at doses equivalent to the total daily dose used in acquired
immunodeficiency syndrome patients. After 19 days, the AZT-treated myotubes in
tissue culture exhibited abnormal mitochondria characterized by proliferation…,
enlarged size, abnormal cristae and electron-dense deposits in their matrix.
The changes were partially reversible after AZT withdrawal. Rats treated with
AZT developed weight loss, 100-fold elevation of creatine kinase, and increased
serum lactate and glucose.” Corcuera-Pindado et al reported Histochemical
and ultrastructural changes induced by zidovudine in mitochondria of rat
cardiac muscle in the European
Journal of Histochemistry in 1994: “We carried out an ultrastructural and
histoenzymatic study in rat cardiac muscle. Groups of animals (3 rats per
group) were given drinking water with or without AZT (1 or 2 mg AZT/ml). After
30, 60 and 120 days, the hearts were studied by light and electron
microscopy... The ultrastructural study showed a disruption of cristae and an
increased size of mitochondria in rats treated with AZT for 30- and 60-days.”
Lewis et al reported that Zidovudine induces molecular, biochemical,
and ultrastructural changes in rat skeletal muscle mitochondria in the Journal of Clinical Investigations in
1992: “Molecular changes in a rat model of AZT-induced toxic myopathy in vivo helped define pathogenetic
molecular, biochemical, and ultrastructural toxic events in skeletal muscle and
supported clinical and in vitro
findings. After 35 d of AZT treatment, selective changes in rat striated muscle
were localized ultrastructurally to mitochondria, and included swelling,
cristae disruption, and myelin figures. Decreased muscle mitochondrial (mt)
DNA, mtRNA, and decreased mitochondrial polypeptide synthesis in vitro were found in parallel.
Mitochondrial molecular changes occurred in absence of altered abundance of
cytosolic glyceraldehyde-3-phosphate dehydrogenase, or sarcomeric mitochondrial
creatine kinase mRNAs.” [10] In his answer to my essay, Martin admits that
AZT destroys bone marrow, but then hedges: HIV “may” be the real culprit. This
is a tired old tale rehashed. Mercury and arsenic salts - doctors’ favourites
for ages - poisoned the patient, whose death was then blamed on unbalanced
humours or germs. That AZT destroys bone marrow is frankly declared by its
manufacturer. So let’s not fudge. In 1987 in Annals of Internal Medicine, Gill et al reported Azidothymidine
Associated with Bone Marrow Failure in the Acquired Immunodeficiency Syndrome
(AIDS): “Four patients with [AIDS], and a history of Pneumocystis carinii
pneumonia developed severe pancytopenia [marked decrease in all types of blood
cells]…12 to 17 weeks after the initiation of azidothymidine therapy… Partial
bone marrow recovery was documented within 4 to 5 weeks in three patients, but
no marrow recovery has yet occurred in one patient during the more than 6
months since AZT treatment was discontinued.” In the same year in the New England Journal of Medicine Richman et al reported The Toxicity of Azidothymidine (AZT) in the Treatment of Patients with
AIDS and AIDS-Related Complex: “Anemia…developed in 24% of AZT recipients
and 4% of placebo recipients (P<0.001). 21% of AZT recipients and 4% of
placebo recipients required multiple red-cell transfusions (P<0.001).
Neutropenia (<500 cells per cubic millimeter) occurred in 16% of AZT
recipients, as compared with 2% of placebo recipients (P<0.001).” The next
year, Walker et al followed up in Annals of Internal Medicine reporting Anemia and erythropoiesis in patients with
the acquired immunodeficiency syndrome (AIDS) and Kaposi sarcoma treated with
zidovudine: “In the current study, transfusion-dependent anemia occurred in
6 of 15 patients with AIDS and Kaposi sarcoma who were receiving zidovudine
therapy. All 6 affected patients required their first blood transfusion between
3 and 9 weeks after starting zidvoudine therapy, and each required 4 to 14
units of packed erythrocytes to maintain a hemoglobin level above 100 g/L over
a 12-week study.” Consistent with this, Costello reported in the same year, in the
Journal of Clinical Pathology that,
“Blood transfusion is often necessary in patients with AIDS, especially in
those receiving AZT, a drug which produces severe anaemia in a proportion of
recipients. Forty nine (36%) of 138 patients treated with AZT required blood
transfusion at least once.” For AIDS doctors slow to the point, Harrison’s Principles of Internal Medicine spells
it out: “[AZT], used for treating [HIV], often causes severe megaloblastic
anemia…caused by impaired DNA synthesis.” Even in the modern age where AZT
dosing levels are now hugely reduced, in 1998, in the New England Journal of Medicine, Hymes et al investigated and reported The
Effect of Azidothymidine on HIV-related Thrombocytopenia, and found again:
“The hematocrit [red blood cell count] decreased in the same patients...with
three of eight patients requiring red-cell transfusion by the fourth week of
treatment.” So did Mocroft et al in their paper in AIDS in 1999: Anaemia is an
independent predictive marker for clinical prognosis of HIV-infected patients
from across Europe: “We found that 78.2% of the [HIV-infected] patients
with mild or severe anaemia at baseline had received zidovudine”. [11] In their
1988 paper in the British Journal of
Haematology, entitled, 3’-Azido-3’-deoxythymidine
inhibits proliferation in vitro of human haematopoietic progenitor cells,
Dainiak et al reported their
investigation of “the mechanism by which cytopenias develop [i.e.
cell depletion, which is]…a serious, dose limiting toxicity of AZT therapy…”
Observing that “Anaemia [during AZT therapy] appears to be due to bone marrow
suppression [and] nearly one half of patients treated with AZT for
[HIV]-associated disease develop transfusion-dependent anaemia due to bone
marrow depression”, they concluded from their study that “AZT is a potent
inhibitor of haematopoiesis in vitro,
and that erythroid progenitors are particularly sensitive to its action. These
results may explain the marrow hypoplasia that occurs during AZT administration
in vivo.” [12] AZT
reaches and can destroy foetal bone marrow too. In the May 1998 issue of the Pediatric Infectious Diseases Journal,
Watson et al at the University of
Rochester Medical Center in New York reported the case of an HIV-negative baby
born to a positive mother who had been treated with a HAART cocktail of AZT,
3TC and a protease inhibitor, suffering “high output congestive heart failure
secondary to profound anemia.” The paediatricians excluded “infection,
nutritional deficiencies, congenital leukemia and congenital red blood cell
aplasia in the child” and considered the “cause of the life-threatening anemia
in our infant…to be in utero erythroid marrow suppression by one or more of the
antiretroviral agents administered to the mother.” [13] Martin
alleges that “toxicity in most cases is reversible.” This optimistic jive was
flatly contradicted by Mir and Costello just a year after AZT was approved.
They reported their concern in the Lancet
in 1988 that “bone marrow changes in patients on zidovudine seem not to be
readily reversed when the drug is withdrawn. These findings have serious
implications for the use of zidovudine in HIV positive but symptom-free
individuals.” [14] Writing
in AIDS in 1997, Kelleher et al noted, “Lack of strong evidence
exists for sustained immune reconstitution by current therapies [comprising AZT
and other drugs, and AZT may] unmask silent opportunistic infections.” Not only
can AZT “unmask silent opportunistic infections”, it can exacerbate clinically
conspicuous ones. Havlir and Barnes reported in February 1999 in the New England Journal of Medicine that
HIV-positive tuberculosis patients treated with [AZT-based] ‘antiretroviral
therapy’ developed “paradoxical worsening of disease…in up to 36 percent of
[them], characterized by fever, worsening chest infiltrates on radiograph, and
peripheral and mediastinal lymphadenopathy…[whereas] only 7 percent of patients
who received antituberculosis therapy but not antiretroviral therapy had
paradoxical reactions.” On 18 September 2000, Reuters released a report Doctors
describe AIDS patients’ medical paradox. It could have been written by a
deadpan standup comedian: “Some AIDS
patients whose ravaged immune systems have been boosted by taking cocktails of
powerful medicines [not even the manufacturers claim this] have been suffering
a surprising increased susceptibility to infections, researchers said on
Monday. Scientists at Thomas Jefferson University in Philadelphia labeled as a
medical paradox their discovery that AIDS patients whose conditions had been
improving [according to surrogate markers, not actual health] thanks to
treatment with drug cocktails had been coming under attack from opportunistic
infections that ordinarily should not have been much of a problem. In a study
published [in September] in the journal Annals
of Internal Medicine, the researchers said the sometimes-fatal ‘immune
reconstitution syndrome’ stemmed from an inflammatory reaction by the newly
strengthened immune system to bacteria or viruses already present in the
patient. The researchers said the causes of the syndrome were unknown. The
researchers said they were startled by the fact that the infections were
affecting patients who had been benefiting from so-called highly active
antiretroviral therapy (HAART) involving the use of combinations of powerful
anti-HIV (human immunodeficiency virus) medicines. The doctors described
learning of patients with a typical infection suffered by those with HIV -
mycobacterium avium infection… ‘No one is exactly sure what to do against this
syndrome yet,’ DeSimone said... More than a year ago, researchers began to see
patients with HIV, the virus that causes AIDS, developing infections at times
that caught them off guard. The Jefferson doctors said they decided to search
the medical literature and speak with colleagues to learn whether others had
seen similar developments. They said doctors at other hospitals mentioned
infections such as CMV retinitis, an AIDS-related blindness...” A subject to
which we will return later. In the case of children, apart from being poisonous
to their blood cells, McKinney et al
found that AZT didn’t alleviate their secondary infections. In their paper A multicenter trial of oral zidovudine in
children with advanced human immunodeficiency virus disease published in the New England Journal of Medicine in 1991, they reported, “Although
no control group was available for direct comparison, the improvement in the
children in this study closely paralleled the observations in controlled
studies of adults receiving zidovudine… Children treated with zidovudine
continued to have bacterial and opportunistic infections.” Of the eighty eight
children in the study, “One or more episodes of hematologic toxicity occurred
in 54 children (61 percent) and neutropenia (neutrophil count, <0.75X10^9
per liter) in 42 (48 percent).” So why prescribe it? [15] Martin’s
happy claim that AZT cocktails afford “long-lasting beneficial effects” was
refuted in November 1997, when Lemp et al
reported in the Journal of Acquired
Immune Deficiency Syndrome and Human Retrovirology that with HAART (Highly
Active Antiretroviral Therapy), “the treatment benefit is temporary and confers
no long-term survival advantages.” Obviously. How could it possibly? Would you
nurse your wilting pot-plant with weed-killer? In the clever age, whatever
happened to common sense? At last some lay folk are waking up; Steven Gendin
wrote an article in the January 1999 issue of the AIDS-drugs-promoting rag POZ, candidly entitled If the virus doesn’t get you, the drugs you
take will. He’s seen enough of his friends fade away on AZT to know. In
July 2000 he went himself at the age of 34, dead of heart failure - which we
will examine below. [16] That AZT
is entirely ineffective as a therapy was borne out clearly by the large-scale
Concorde trials in Europe, reported by the Coordinating Committee in the Lancet in April 1994: “A total of
172…participants died [169 while taking AZT, 3 while on placebo] …The results
of Concorde do not encourage the early use of zidovudine in symptom-free
HIV-infected adults.” Embarrassingly
for Wellcome, and disastrously for its share prices, the fabulous results of
the chaotic American study that had preceded FDA approval of AZT couldn’t be
reproduced. The drug was found to have no clinical benefits. Predictably,
“Representatives of the Wellcome Foundation who were also members of the
Coordinating Committee…declined to endorse this report” and insisted on
gerrymandering the reach of its grim conclusions. Even so, the adverse implications
of the trial for AZT could not be avoided. One glaring finding was that AZT’s
“severe side-effects”, even in cases of patients on low doses quashed any
apparent therapeutic value as suggested by raised CD4 cell-counts - about which
the Committee noted that the results “also call into question the uncritical
use of CD4 cell counts as a surrogate endpoint for assessment of benefit from
long-term antiretroviral therapy.” Emphasising the worthlessness of CD4 cell
counting in Annals of Internal Medicine
in 1996, Fleming and DeMets described it as being “as uninformative [an
indication of immune status] as a toss of a coin.” Not that anyone took any
notice. Today, patients terrified by their doctors’ mournful announcements of
their low cell counts - still taken as a signal of collapsing health and
imminent demise - are urged to start with ‘antiretrovirals’ like AZT, following
which the prophesy will be faithfully fulfilled. For example, Harrigan et al reported in AIDS in July 2000 that “Triple therapy for
HIV-infected patients… do not have any unique effects on CD4 cell counts
independent of reductions in plasma viral load”, according to Reuters; “The data appear to contrast
with recent evidence suggesting that such regimens are able to maintain an immunologic
benefit even after plasma viral rebound… The team examined the correlation
between CD4 cell counts and plasma viral load over 52 weeks using data from 3
randomized clinical trials… The studies compared dual nucleoside therapy with
triple combination therapy that included a protease inhibitor, with or without
a nonnucleoside reverse transcriptase inhibitor. The data presented in these
randomized double-blinded trials suggest that the specific antiretroviral
regimen used neither increases nor decreases the strength of the correlation
between the change in CD4 cell count and the change in plasma viral load.” CD4
cell counting continues to the present day, as if it means anything. And the
evidence mounts against multi-drug therapy, a topic deferred for a later look. [17]
Notwithstanding the dark clouds looming over AZT at the end of the Concorde
trials, Wellcome released ebullient press statements quite at variance with the
negative findings that the trial overseers were later to report in the
Lancet. But the company could hardly endorse a finding and broadcast to the
world that a flagship money-spinner didn’t live up to its billing. To obfuscate
the drug’s demonstrated therapeutic irrelevance, and keep a good thing going
for the company’s bottom line, Wellcome pulled a sharp move. To protect its
delinquent product, it immediately threw its support behind a new gimmick
called ‘combination therapy’. Henceforth the dose was slashed in half or more,
and AZT was to be marketed as a drug combined with others - all equally
ineffective on their own, as if to mix two or three toxic duds would be to
conjure them miraculously into a medicinal marvel. It’s a treatment approach
that is now falling to pieces, as we’ll see when we review the recent
literature about HAART cocktails later on. But before we leave the subject of
mixing your drinks, just in is a paper by Havlir et al in the July 2000 issue of the Journal of Infectious Diseases warning for heaven’s sake don’t take
AZT and 4TC together. Reuters Health
reported: “Combination treatment with zidovudine and stavudine results in worse
outcome than treatment with stavudine alone, according to the results of a
48-week multicenter study…The researchers conclude that stavudine and
zidovudine should not be used together in any antiretroviral regimen.” Now you
tell us. [18] In fact, not only was
AZT found to be useless at the end of the Concorde trials, it turned out to be
positively harmful: Phillips et al
reported in a letter to the New England
Journal of Medicine in March 1997 that “Extended follow-up of patients in
one (AZT) trial, the Concorde study, has shown a significantly increased risk
of death among the patients treated early.” In another paper in that year, Impact of treatment changes on the
interpretation of the Concorde trial, White et al highlighted in AIDS that
“participants of open-label ZDV [AZT] still had four to five times the
incidence of ARC/AIDS/death of participants on blinded therapy [of which approximately
half were on AZT and half on placebo] … The unadjusted hazard of ARC/AIDS/death
was 4.6 times higher for participants [in the deferred group] who had received
ZDV...after adjustment for latest CD4 this became 1.6 … There was a suggestion
of a benefit in terms of [slower] progression to ARC, AIDS or death [with AZT],
no effect on progression to AIDS or death, and a suggestion of an increase in
mortality.” Walker summed it up in his essay HIV, AZT, big science & clinical failure, “…the Concorde trial
results showed conclusively that asymptomatic antibody-positive individuals who
took AZT, died more quickly and in greater number than those simply affected by
AIDS-defining illnesses.” As Marginal
structural models to estimate the causal effect of zidovudine on the survival
of HIV-positive men in the September 2000 issue of Epidemiology by Hernan et al
suggested too: “Our analysis included the
2,178 men who attended at least one visit between visits 5 and 21 while HIV positive, and who did not have an
AIDS-defining illness and were not on antiretroviral therapy at the first eligible visit. By the end of the
follow-up (media duration-69
months), 1,296 men had initiated zidovudine treatment and 750 had died”,
from which the researchers drew the
dazzling conclusion of “a detrimental
effect of zidovudine.” [19] The
negative Concorde trial results were entirely on par with those of an earlier
French trial. In 1988 in the Lancet,
Dournon et al had published a study
of AZT, conducted at the Claude Bernard Hospital in France. It was wider and
longer than the American Fischl trial that had preceded FDA approval, and at
the end of it the researchers found AZT to be “disappointing.” They noted, “The
bone marrow toxicity of AZT and the frequent need for other drugs with
haematological toxicity meant that the scheduled AZT regimen could be
maintained in only a few patients… by six months, these values [i.e. initial
modulation of p24 antigen levels] had returned to their pretreatment levels and
several opportunistic infections, malignancies and deaths occurred” - by nine
months, about a third dead, another third very sick. But most significantly for
the idea that AZT exerted an anti-HIV effect, “full-dose AZT for 2 months did
not eliminate antigenemia in patients with pretreatment p24 levels of 200 U/ml
or higher...[so] in AIDS and ARC patients, the rationale for adhering to
high-dose regimens of AZT, which in many instances heads to toxicity and
interruption of treatment, seems questionable.” It bears emphasising that the
dose was 200mg every four hours, the standard officially recommended dose, and
the same as the dose given during the pre-approval Fischl trial in the US, yet
the reported outcome was completely different. [20] It is
worth quoting at length from the Claude Bernard Hospital AZT trial report
because it is very illuminating: “AZT was started at full dose in 260 patients,
64 with ARC and 196 with AIDS. In 58 of these patients, AZT had to be stopped
at least once for a minimum of 7 days. In 142 other patients, dosage was
reduced by half because of leucopenia (79), leucopenia and (32), anaemia (20),
rash (3), vomiting (3), headaches and insomnia (2), myalgia (2), or hepatitis
(1). 3 patients reduced the dose with no medical reason. Later on, progression
of toxicity led to suspension of AZT (for at least 7 days) in 85 of the 142
patients whose treatment had been reduced to half dose. Thus AZT was stopped at
least once in 143 (55%) patients who began the full-dose regimen. Because of
their initial haematological status 105 (28.8%%) patients were treated from the
start with half-dose AZT – toxicity led to cessation of treatment in 71 (67.6%)
cases.” [21] One
can’t help wondering whether the fact that the French trial was performed
independently, and beyond the reach and control of the drug’s manufacturer,
might not have had something to do with it. Indeed, Professor David Warrell, UK
chairman of the Concorde trials, commented on Wellcome’s efforts to skew the
final Concorde report as follows: “What we learnt I suppose, and we shouldn’t
have been surprised, is that when the wrong result is produced for a famous and
flourishing company on which a great deal of financial expectation rests, the
company’s representatives are going to be under a great deal of pressure, and
the interpretation of those results is going to be ‘stressed’; there is going
to be an attempt perhaps to blunt the message, to modify, to make a more mellow
conclusion from results which seem to be inescapable in their implications.” [22] Martin’s
absurd statement that AZT and 3TC “improves quality of life” is just stale
advertising propaganda quoted mindlessly from some glossy ad. The trouble that
doctors have with patient ‘non-compliance’ is notorious, due to the
intolerable, excruciating ‘side effects’ that most people experience on these
drugs. Numerous papers have detailed these problems, most recently for example,
Nicholson: Managing side-effects:
practical advice on dealing with side-effects of antiretroviral therapies in AIDS Treatment Update, October 1998. In
1994, Lenderking et al of the Harvard
School of Public Health, reporting their Evaluation
of the Quality of Life Associated With Zidovudine Treatment in Asymptomatic
Human Immunodeficiency Virus Infection in the New England Journal of
Medicine, found “a reduction in the quality of life due to severe side
effects of therapy” and the “severe adverse events” it caused, which were
“life-threatening in some cases.” Without intended irony, AIDS expert Dr. Lori
Swick pointed out in The Toronto Star
in September 1999 that “One of the major barriers to effectively treating HIV
is that most people do not feel sick at the time they are offered anti-HIV
medications. In fact, it is only after starting the medications that they begin
to feel sick.” Well, of course. Jerry Cade MD, who serves on the US
Presidential Advisory Council on HIV/AIDS agrees. In the April 2000 edition of A+U, an AIDS magazine in the US, he
stated, “In the face of extreme drug side effects, some patients … are becoming
extremely ill from the medications.” On 12 July 2000 Business Today quoted AIDS don Anthony Fauci, director of the US
National Institute for Allergies and Infectious Diseases telling the 13th International AIDS Conference in
Durban about the desirability of interrupting the ‘antiretroviral’ treatment
with ‘drug holidays’: “The patients in the study are absolutely delighted to
spend half their time off therapy… Clearly, even our
most vigorous efforts to eradicate (the virus) had been unsuccessful.” The report went on, “Most
patients have a difficult time staying on their anti-HIV drugs because the
effect wears off or the side effects become intolerable. Side effects can
include everything from fever to headaches, from nausea to anemia. Many
patients therefore cannot take the drugs... A separate study reported Tuesday
by Scott Holmberg of the U.S. Centers for Disease Control and Prevention shows
how intolerable treatments can be.” GlaxoWellcome however would prefer you sick
without a break until you go. Its PRODUCT INFORMATION release for Combivir (AZT
and 3TC) states, “Patients should be advised of the importance of taking
COMBIVIR as it is prescribed” i.e. “One COMBIVIR tablet…twice a day.” [23] The
truth of the matter is that AZT makes you feel like you’re dying. That’s
because on AZT you are. How can a deadly cell-toxin conceivably make you feel
better as it finishes you, by stopping your cells from dividing, by ending the
vital process that distinguishes living things from dead things? Not for
nothing does AZT come with a skull and cross-bones label when packaged for
laboratory use. [24] These
are some of AZT’s ‘side effects’ listed by its manufacturer: Body as a Whole:
abdominal pain, back pain, body odor, chest pain, chills, edema of the lip,
fever, flu syndrome, hyperalgesia; Cardiovascular: syncope, vasodilation;
Gastrointestinal: bleeding gums, constipation, diarrhea, dysphagia, edema of
the tongue, eructation, flatulence, mouth ulcer, rectal hemorrhage; Haemic and
Lymphatic: lymphadenopathy; Musculoskeletal: arthralgia, muscle spasm, tremor,
twitch; Nervous: anxiety, confusion, depression, dizziness, emotional lability,
loss of mental acuity, nervousness, paresthesia, somnolence, vertigo;
Respiratory: cough, dyspnea, epistaxis, hoarseness, pharyngitis, rhinitis, sinusitis;
Skin: acne, changes in skin and nail pigmentation, pruritus, rash, sweat,
urticaria; Special senses: amblyopia, hearing loss, photophobia, taste
perversion; Urogenital: dysuria, polyuria, urinary frequency, urinary
hesitancy. [25] A
typical encounter with “A world of antiretroviral experience” promised children
in an AZT advertisement in the Lancet
in 1991 was described in an article by Gayle Melvin, KIDS WITH AIDS, run in several newspapers in the US and Canada in
September 1998: “Robert Swanson’s medicines came with horrible side effects:
nausea, diarrhea and blinding headaches… Robert would secretly skip a dose of
medicine. ‘I’d find his pills all over the place, in his room, in the dirty
clothes’, Britten says… ‘When you think of medicine, you think of something
that makes you better, but I don’t feel better when I take it,’ Robert says.
‘I’d rather feel good and let the virus take over than feel bad and take the
medicine.’ …Tina [takes] AZT,…ddC and Viracept, a protease inhibitor…three times
a day. Then she waits to get sick. ‘My head will start to hurt all over, like a
pounding. I get dizzy. Sometimes I throw up,’ she says in her sweet, girlish
voice. She gets sick every time? ‘Every time’, says Tina… As they go through
their teens, these children face [the] challenges [of] taking responsibility
for their…often debilitating medical regimen.” [26] Gay playwright Larry Kramer, founder of prominent AIDS-activist group ACT-UP, was interviewed on WebMD on 7 January 2000. As he made plain, he’s not opposed in principle to drug treatment for AIDS diseases; on the contrary he said, “I have felt it…important, … to concentrate all my energy on fighting for a cure, fighting for drugs.” He had many revealing observations from the ground about current therapies, mostly AZT-based ‘cocktails’: “I think, for those of us who follow the literature, the medical literature…what’s appearing more and more, is terribly frightening reports that the proteases, the cocktails simply are not working in a larger and larger percentage of people, and that these new drugs that are coming out right, left, and centre have such horrendous side effects that people simply are beginning to refuse to take them…We’re finding out, for instance, that 50 percent of people who take certain drugs die from liver disease rather than AIDS, because the drugs are so harsh on the liver… unfortunately, …most of the activists, the AIDS activists, who speak for us now are so in the pockets of the bureaucracy of the drug companies …, that they have become almost fascist in ramming their treatment notions down the rest of us. The research that is done today is pretty much dictated by a small handful of pea brains called Treatment Action Group, TAG, which has a stranglehold on what is researched, what the drug companies release, how it’s tested, and … the guidelines [for] all of this poison… we really must start putting pressure on the pharmaceutical companies to make us drugs that don’t have such horrible side effects... And more and more people I know are refusing to take drugs at all, which is very interesting. They’d rather just not feel that sick. …And the other thing that nobody pays any attention to is that we simply do not have any data - sufficient data - to know which of these drugs works and in which combination. The drug company makes the drug, unleashes it on the world, goes on to merrily develop another poison without continuing to test the stuff that’s out there. There is no database that is worth anything… If after only two years, the combination therapies are beginning to make people so sick and kill them, how are you supposed to take them for the rest of your life? Get real… I said to a friend of mine, David Sanford, who’s editor of the Wall Street Journal, who has AIDS, and who just feels so awful from all of these drugs, and I said ‘why don’t you get out there and say I feel awful from all these drugs?’ …I think it’s very interesting that I am hearing about more and more patients who are simply stopping taking the medicine. They’re just too uncomfortable.” Also participating in the interview was Dr. Richard Marlink, senior research director and lecturer at the Department of Immunology and Infectious Diseases at the Harvard School of Public Health, and executive director of the Harvard AIDS Institute. He heartily agreed with Kramer’s concern that “the fact that that database does not exist anywhere” and thought it was “a national crime.” [27] The extreme liver toxicity of AZT mentioned by Kramer has long been observed, and it has recently been formally acknowledged again. In 1989, in Annals of Internal Medicine, Dubin et al found Zidovudine-induced hepatotixicity: “We report a patient who experienced acute cholestatic hepatitis on initial exposure to and rechallenge with zidovudine and, as a result, was unable to receive further therapy with the drug... Seven days [after starting AZT therapy] the patient presented with a 2-day history of intermittent fevers and abdominal discomfort... Seven days [after re-starting AZT therapy once the initial symptoms resolved] the patient again experienced fever, right upper quadrant pain, nausea, and headache... One month later [after dis |