[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readily reversed when the drug is withdrawn.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 discontinuing AZT] the
liver function tests had almost completely returned to normal and remained
without significant abnormalities.” In 1990, during a stint at Mount Sinai
School of Medicine, Professor Allen Arieff reported several cases of fatal
lactic acidosis among patients treated with AZT. Reports of AZT-generated liver
disease were also fielded by the National Institutes of Health. The numerous
cases turned up by FDA epidemiologist Joel Freiman led to the FDA demanding
that Burroughs Wellcome issue an advisory to leading infectious disease
specialists in the US about the danger that AZT treatment posed to the liver. Which
it did in 1993. It went unheeded.
Perhaps because the AZT PRODUCT INFORMATION advisory still says, “There
are insufficient data to recommend dose adjustment of Retrovir in patients with
impaired hepatic function.”
[28] On 19 November 1999 Reuters Health reported that “Liver
disease has become the leading cause of death among HIV patients at a
Massachusetts hospital, [according to] a report issued on Friday...[by] Dr.
Barbara McGovern, a professor at Tufts University School of Medicine and a
member of staff at Lemuel Shattuck Hospital in Jamaica Plains, Mass. The
findings were reported…at the annual meeting of the Infectious Diseases Society
of America in Philadelphia. McGovern said HIV patients who take a powerful
combination of AIDS drugs called highly active antiretroviral therapy (HAART)
were at particular risk because of the drug’s potential toxicity to the liver.
One-third of HIV patients with underlying liver disease at Lemuel Shattuck have
had to stop taking HAART.” In the same month, in their paper HIV Treatment-Associated Hepatitis,
Orenstein and LeGall-Salmon reported in The
AIDS Reader that “Severe hepatitis has been reported with all of the
currently available classes of antiretroviral agents.”
[29] In a case report
published in August 2000 in Infections in
Medicine entitled Lactic Acidosis
Secondary to Nucleoside Analog Antiretroviral Therapy, Khouri and Cushing explain why drugs in the AZT class hammer the
liver: “There are several reports of lactic acidosis and microvesicular
steatosis-associated nucleoside analog toxicity in HIV-infected patients… The
patients were treated with zidovudine and had a high mortality rate… Seven
reports have described the syndrome of lactic acidosis in 25 patients with
HIV/AIDS… Of the total, 21 were receiving treatment with zidovudine, and 1 was
receiving treatment with stavudine, lamivudine, and indinavir. Sixteen (64%) of
the patients were female, and 18 (72%) died… The nucleoside analog
antiretroviral agents…inhibit mitochondrial DNA (mtDNA) polymerase in cell
culture…. Zalcitabine, stavudine, zidovudine, and didanosine all have an effect
on mtDNA synthesis… Inhibition of mtDNA can lead to a variety of metabolic
abnormalities. These are largely the result of a derangement in pyruvate
metabolism. After formation by glycolysis, pyruvate is metabolized in the
mitochondria by pyruvate dehydrogenase (PDH) to acetyl coenzyme A (CoA).
Pyruvate may be reduced to lactate by lactate dehydrogenase, and it may also be
used in gluconeogenesis… Inhibition of mtDNA causes a disorder of oxidative
phosphorylation by making the mitochondrial respiratory chain dysfunctional and
unable to break down acetyl CoA. This dysfunction shifts pyruvate metabolism
toward the other pathways, reduction to lactate and gluconeogenesis. The lactate
cannot be cleared as rapidly as it is being produced, and the resultant excess
causes an acidosis. The increased gluconeogenesis causes hyperglycemia. Even
though the inhibition of polymerase g makes the respiratory chain
dysfunctional, PDH is fully functional and makes acetyl CoA. The overproduction
of acetyl CoA, without utilization in the respiratory chain complex, pushes it
out of the mitochondria and into the cytoplasm, where it serves as a substrate
for fat production… Inability to metabolize acetyl CoA also leads to increased
circulating levels of the ketones acetoacetate and b hydroxybutarate… Suggested
mechanism and manifestations of mitochondrial dysfunction. (A) The nucleoside
analog antiretroviral agents inhibit mitochondrial DNA (mtDNA) polymerase g in
cell culture. Inhibition of mtDNA makes the mitochondrial respiratory chain
dysfunctional and unable to break down acetyl coenzyme A (CoA). This shifts
pyruvate metabolism toward the other pathways, reduction to lactate and
gluconeogenesis. The lactate cannot be cleared as rapidly as it is produced and
the resultant excess causes an acidosis. (B) The increase of pyruvate leads to
increased gluconeogenesis in the liver, resulting in secondary diabetes
mellitus. The gluconeogenesis stimulates insulin production. (C) The
overproduction of acetyl CoA without utilization in the respiratory chain
complex pushes it out of the mitochondria to the cytoplasm, where it serves as
a substrate for fat production. (D) The overproduction of lactate causes lactic
acidosis. The gluconeogenesis causes the secondary diabetes mellitus and
hyperinsulinemia, the hyperinsulinemia causes insulin resistance, and fat
synthesis causes fatty liver and weight gain…. The predicted clinical
manifestations of mitochondrial dysfunction are fatigue from decreased levels
of adenosine triphosphate production, lactic acidosis, ketoacidosis, secondary
diabetes mellitus, and fatty liver and weight gain caused by hyperglycemia.”
[30] As for
the fabled power to prevent pregnant women transmitting HIV to their foetuses
that Martin claims for AZT, Bennet warned in Mandatory testing of pregnant
women and newborns: a necessary evil? in AIDS/STD Health Promotion
Exchange 1998
that “At present, data regarding the effects of ZDV (AZT) use on vertical
transmission rates are inconclusive and incomplete. In addition, the long-term
effects of ZDV use during pregnancy and after birth on the woman and any
resulting child are yet to be discovered. The possibility has not yet been
ruled out that this ‘risk-reducing’ measure may not be effective and may prove
detrimental to the health of both mother and child.”
[31]
Bennet’s caveat has moved from the hypothetical to the tragically real. In
February 1999, French researcher Stephane Blanche announced at the Sixth
Conference on Retroviruses and Opportunistic Infections that the drug had
apparently killed two babies in an AZT trial that he and colleagues were
conducting. Both had fallen sick at four months and had died of mitochondrial
dysfunction and neurological defects - conditions ordinarily very rare. In
September 1999, in his research team’s paper in the Lancet entitled Persistent
mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside
analogues, he reported: “We analysed observations of a trial of tolerance
of combined zidovudine and lamivudine and preliminary results of a continuing
retrospective analysis of clinical and biological symptoms of mitochondrial
dysfunction in children born to HIV-1-infected women in France.... Eight
children had mitochondrial dysfunction. Five, of whom two died, presented with
delayed neurological symptoms (epilepsy, massive cortical necrosis, cortical
blindness, spastic tetraplegia, cardiomyopathy and muscle weakness) and three
were symptom-free but had severe biological or neurological abnormalities. Four
of these children had been exposed to combined zidovudine and lamivudine, and
four to zidovudine alone. No child was infected with HIV-1... Our findings
support the hypothesis of a link between mitochondrial dysfunction and the
perinatal administration of prophylactic nucleoside analogues… Further
assessment of the toxic effects of these drugs is required.” On the same theme,
in the same issue of the Lancet,
Dutch researchers Brinkman et al
published a paper recording their view that AZT-class drugs “are much more
toxic than we considered previously.” Discussing the body-wasting
characteristic of AZT-treated patients, they point out that “The layer of
fat-storing cells directly beneath the skin, which wastes away…is loaded with
mitochondria… [O]ther common side effects of [AZT and like drugs are] nerve and
muscle damage, pancreatitis and decreased production of blood cells… all
resemble conditions caused by inherited mitochondrial diseases.” In July 1999,
ahead of publication of Blanche et al’s
report, the Committee on Safety of Medicines in the United Kingdom issued a
warning to doctors “about the risk of mitochondrial dysfunction in infants born
to HIV infected mothers treated with zidovudine (AZT) to prevent vertical
transmission” according to the AIDS information service, www.aidsmap.com: “The warning comes in
advance of the publication of data from a French study in which it was
discovered that 8 out of approximately 200 infants developed mitochondrial
dysfunction following exposure to zidovudine, with or without 3TC treatment,
for the prevention of vertical transmission of HIV infection.” And without
giving further details, on 3 February 2000 Laurie Garrett reported in Newsday,
“But two babies have died
recently in the United States as a result of AZT-induced destruction of their
mitochondria, vital components of all human cells....” Nonetheless, “surprising
to outside observers was Mbeki’s decision to deny the use of AZT, which is very
cheap, to block the transmission of the virus from mother to baby even though
the drug was offered at a dramatically discounted rate.”
[32]
Blanche’s hypothesis that AZT - a well-established mitochondrial poison in
adults - damaged mitochondria in utero
found support in Gerschenson et al’s
paper in May 2000 in AIDS Research and
Human Retroviruses, reporting Fetal
mitochondrial heart and skeletal muscle damage in Erythrocebus patas monkeys
exposed in utero to 3'-azido-3'-deoxythymidine: “3’-azido-3’-deoxythymidine
(AZT) is given to pregnant women positive for the human immunodeficiency virus
type 1 (HIV-1) to reduce maternal-fetal viral transmission. To explore fetal
mitochondrial consequences of this exposure, pregnant Erythrocebus patas
monkeys were given daily doses of 1.5 mg (21% of the human daily dose) and 6.0
mg (86% of the human daily dose) of AZT/kg body weight (bw), for the second
half of gestation. At term, electron microscopy of fetal cardiac and skeletal
muscle showed abnormal and disrupted sarcomeres with myofibrillar loss. Some
abnormally shaped mitochondria with disrupted cristae were observed in skeletal
muscle myocytes. Oxidative phosphorylation (OXPHOS) enzyme assays showed
dose-dependent alterations. At the human-equivalent dose of AZT (6 mg of AZT/kg
bw), there was an approximately 85% decrease in the specific activity of NADH
dehydrogenase (complex I) and three- to sixfold increases in specific activities
of succinate dehydrogenase (complex II) and cytochrome-c oxidase (complex IV).
Furthermore, a dose-dependent depletion of mitochondrial DNA levels was
observed in both tissues. The data demonstrate that transplacental AZT exposure
causes cardiac and skeletal muscle mitochondrial myopathy in the patas monkey
fetus.”
[33] American researchers
(Culnane et al), who in January 1999
had claimed in the Journal of the
American Medical Association that AZT appeared to be safe for babies, were
incredulous when Blanche dropped his conference bombshell. Which is odd,
because a month earlier a paper in AIDS
by Lorenzi et al at Hopital Cantonal Universitaire in Geneva
reported that “Following combination antiretroviral therapy administered during
pregnancy, most HIV-positive mothers and about half of their children developed
one or more adverse events.” Of thirty babies, “the most common adverse event
was prematurity (ten infants), followed by anaemia (eight). The investigators
also noted two cases of cutaneous angioma, two cases of cryptorchidism, and one
case of transient hepatitis. Two infants…developed… intracerebral
hemorrhage…[and one,]…extrahepatic biliary atresia.”
[34] None of this is really
surprising since as early as 1990, Gillet et
al had reported in the Journal of
Gynecology, Obstetrics, and Biological Reproduction that “concentrations of
[AZT] in the liquor and in the fetal blood [of six aborted human foetuses] were
higher or equaled those found in the maternal blood.” They reiterated
accordingly, “The drug remains contra-indicated in pregnancy.” Not least
because the FDA categorises AZT as a ‘C’-class drug for safety in pregnancy.
With such drugs, it warns, “Safety in human pregnancy has not been determined,
animal studies are either positive for fetal risk or have not been conducted,
and the drug should not be used unless the potential benefit outweighs the
potential risk to the fetus.” Stahlmann and Klug concurred in Antiviral Agents: Nucleoside and
Non-nucleoside Analogues in Kavlock and Dastron’s text, Drug Toxicity in Embryonic Development.
Advances in Understanding Mechanaisms of Birth defects: Mechanisting
Understanding of Human Development Toxicants: “Sufficient data regarding
the safety of zidovidine in human pregnancy are not available.”
[35] In their paper
published in Mutation Research in
1997, Genotoxicity and Mitochondrial
Damage in Human Lymphocyte Cells Chronically Exposed to AZT, Argawal and
Olivero reported that “AZT induces significant toxic effects in humans exposed
to therapeutic doses… Cytogenetic observations on H9-AZT cells showed an
increase in chromosomal aberrations and nuclear fragmentation when compared
with unexposed H9 cells [and] the mechanisms of AZT induced cytotoxicity in
bone marrow of the patients chronically exposed to the drug in vivo may involve both chromosomal and
mitochondrial DNA damage.” This might explain Kumar et al’s 1994 report in the Journal
of Acquired Immune Deficiency Syndrome and Human Retrovirology of a
shocking number of therapeutic and spontaneous abortions, and, in the case of
live births, a ten per cent
abnormality rate among one hundred and four cases of pregnant women treated
with AZT in a hospital in India. The grotesque birth defects included holes in
the chest, abnormal indentations at the base of the spine, misplaced ears,
mis-shapen faces, heart defects, extra digits and albinism. Such birth defects
are not unknown among Western children exposed to AZT in the womb either;
interviewed in Zenger’s magazine in
September 1999, Mary Caffrey, a nurse in the Paediatric Division of the
University of San Diego Medical Center, said reassuringly about AZT-generated
birth defects, “I know we’ve seen some webbed fingers...but these birth defects
are cosmetic and don’t interfere with life.” The almost trebled birth defect
rate in the state of New York among babies exposed to AZT in the womb was
reported by Newschaffer et al in July
2000 in the Journal of the Acquired
Immune Deficiency Syndrome. The epidemiologists researched Prenatal Zidovudine Use and Congenital
Anomalies in a Medicaid Population “in 1932 liveborn deliveries from 1993
to 1996 to HIV-infected women in the state of New York (NYS), U.S.A. Prevalence
of anomalies in the cohort was compared with that of a general NYS population.
Within the cohort, adjusted odds of any anomaly were compared by receipt of ZDV
and by trimester of first prescription.” They found that “The adjusted
prevalence of any anomaly in the study cohort was 2.76 times greater than in
the general population … Children of study women who were prescribed ZDV had
increased adjusted odds of any anomaly… Children of HIV-infected women in this
cohort had a greater prevalence of major anomalies than did the general NYS
population...” Doesn’t the doctor’s Hippocratic promise not to administer
poison apply anymore?
[36] The
danger for developing foetuses posed by the administration of AZT to pregnant
mothers was underscored in 1997 by Ha et
al in the Journal of Acquired Immune
Deficiency Syndrome and Human Retrovirology in their paper entitled Fetal, infant, and maternal toxicity of
zidovudine (AZT) administered throughout pregnancy in Macaca nemestrina.
The researchers reported, “The AZT animals [Macaque monkeys given AZT during
pregnancy] developed an asymptomatic macrocytic anemia, but hematologic
parameters returned to normal when AZT was discontinued. Total leukocyte count
decreased during pregnancy and was further affected by AZT administration.
AZT-exposed infants were mildly anemic at birth. AZT caused deficits in growth,
rooting and snouting reflexes, and the ability to fixate and follow near
stimuli visually.” The latter indications of neurological damage were
anticipated in their 1994 paper in the same journal, Fetal toxicity of zidovudine in Macaca nemestrina: preliminary
observations. They found that “AZT-exposed infants took three times as many
sessions (6) as controls (2) to meet criterion on Black-White Learning, a
simple discrimination task (and were)…significantly [worse in locating] the
reward…” That’s not all they found either: “Postnatal weight increase was
significantly lower in AZT-exposed infants… Hemoglobin dropped significantly in
the AZT-treated animals after treatment began and remained low until the end of
the study... Platelet counts increased significantly in AZT-treated animals
during the treatment period but returned to control levels before the end of
the study... The mechanism for the elevation of platelet count in AZT-treated
animals is unknown… The hematological toxicities reported here are consistent
with those seen in 500 mg/day AZT-treated humans.” Incredibly, Connor et al in their piece (discussed in my
first essay) Reduction of Maternal-Infant
Transmission of Human Immunodeficiency Virus Type 1 with Zidovudine Treatment,
the pitiful albeit hugely popular paper in the New England Journal of Medicine in 1994 propounding the
administration of AZT to pregnant women, rely on Ha et al’s just-mentioned
1994 monkey research report for the comforting conclusion, “Based on these
findings, we predict that there would be no significant toxic effects of
prenatal AZT exposure (100 mg/dose; 500 mg/day) in humans.” In the light of all
that was already known about the acute toxicity of AZT, and it would be
reinforced by later studies, what better illustration of Erasmus’s foresight in
the 16th century that the dullest, most ignorant and incautious
doctors would become the superstars of the AIDS age, and that for their
experiments on pregnant women with cell-poisons they’d be not abjured but celebrated.
On trial, no doubt, they would defend their science in radical ideological
terms like the doctors at Nuremberg. The evil they perceived called for
ruthless measures to root out, and in such struggles conventional civilised
restraints on medical experiments on humans fall by the way.
[37] AZT is
as poisonous to children as it is to the unborn: In a study in the US, designed
by Dr. Janet Englwood, and sponsored by both the National Institute of
Allergies and Infectious Diseases and the National Institute of Child Health
and Human Development, eight hundred and thirty nine HIV-positive children were
divided into three groups and treated with AZT, ddI and a combination of both
respectively. The ‘AZT alone’ wing of the study had to be called off abruptly
in February 1995 due to the “more rapid rates of…bleeding and biochemical
abnormalities” exhibited by the children in this group. For the reason, here’s
a clue. In 1997, Benbrick et al
reported a study by researchers at several French institutions in the Journal of Neurological Science;
comparing AZT with other similar nucleoside analogue drugs used in AIDS
treatment, they found that although “all [such drugs] exert cytotoxic effects
on human muscle cells and induce functional alterations of mitochondria…AZT
seemed to be the most potent inhibitor of cell proliferation.”
[38] Consonant with these
findings, in 1997 in the journal Clinical
Infectious Diseases, Heresi et al
reported fungal infestations (PCP) which developed in the lungs of two
HIV-negative babies, born healthy, whose mothers had been treated with AZT
followed by the babies themselves for six weeks. No mystery about it. Under the
entry ‘Retrovir’ (AZT’s trade name), The
Physician’s Desk Reference hints
delicately, “It was often difficult (in AZT clinical trials) to distinguish
adverse events possibly associated with administration of Retrovir from
underlying signs of HIV disease or intercurrent illnesses.” In similar terms,
the 16th edition of the manual USP
DI: Drug Information for the Health Care Professional published in 1996 by
the United States Pharmacopeial Convention states that “it is often difficult
to differentiate between the manifestations of HIV infection [again presumed]
and the manifestations of zidovudine. In addition, very little placebo
controlled data is available to assess this difference.” To put a point on it,
AZT itself can cause AIDS-defining illnesses. Its critics have been saying so
for years. What else is one to make of Buchbinder et al’s finding reported in AIDS
in 1994 that “Only 38% of the HLP (healthy long-term (>10 years)
positives) had ever used zidovudine or other nucleoside analogues, compared
with 94% of the progressors”? Or Washington University’s Assistant Professor of
Medicine Dr Carl Fichtenbaum’s observation about Mycobacterium avium complex
disease in his article I Hear You
Knockin’ in the magazine Research
Initiative Treatment Action: “Mycobacterium avium complex disease is one of
the most common OI’s [opportunistic infections] in persons with advanced HIV
disease. It has been observed in 15 to 40% of persons with HIV infection. The
incidence of MAC began rising in 1987 in persons with AIDS. From 1981 to 1987,
5.3% of persons with AIDS reported to the CDC had MAC disease. Of note, the
incidence increased from 5.7% in 1985-86 to 23.3% in 1989-90. Thus, MAC disease
has become one of the most frequent OI events occurring in individuals with
CD4+ lymphocyte counts <50 cells/mm3.” Funny how the disease incidence
suddenly ballooned coincidentally with the introduction of AZT as an AIDS drug
in 1987.
[39] In a
remarkable illustration of how AIDS doctors miss the grisly evidence of the
iatrogenic cause of their patients’ disease right in front of their eyes,
Swanson et al published a report in AIDS in 1990 entitled
Factors influencing outcome of treatment
with zidovudine of patients with AIDS in Australia: “Zidovudine was
reasonably well tolerated in this study... 27% [remained] on full dose at the
end of the first year of therapy. The full daily dose (1.2 g) was received by
68 patients (24%) for the entire duration of their time on therapy. Of these
full-dose patients, six died within 6 weeks of commencing therapy...172
patients (56%) developed a new AIDS-defining condition during therapy; 130
patients [42%] developed the condition more than 6 weeks after commencing
zidovudine therapy... Anemia was the most frequently reported adverse
experience during zidovudine therapy. Transfusions were reported necessary for
155 patients (50%) while on zidovudine, 91 patients (representing 29% of the
total) required transfusions on more than one occasion.” With a similar
detached Josef Mengele tone, in Prolonged
zidovudine therapy in patients with AIDS and advanced AIDS-related complex,
Fischl et al reported a year earlier
in the Journal of the American Medical
Association, “58% of all subjects with AIDS and AIDS-related complex
receiving zidovudine experienced granulocytopenia of grade 3 or higher...
Serious anemia occurred in 32% of all subjects receiving zidovudine...and could
be typically managed by dose attenuation, temporary dose interruption of
zidovudine therapy and/or red blood cell transfusions... 12% of subjects...had
an episode of thrombocytopenia after the initiation of zidovudine therapy...
Ten patients had liver enzyme levels elevated...and were managed with dose
attenuations or interruptions of zidovudine therapy... One report of a grand
mal seizure, two events associated
with cardiac dysfunction, and five reports of myopathy were the only new
serious potentially drug-related adverse events reported during extended
periods of zidovudine administration.”
[40] In the June 1999 issue
of the New England Journal of Medicine,
Learmont et al reported the
interesting case of eight “transfusion recipients…infected with…HIV-1…from a
single donor before 1985… Since then, two subjects died of causes unrelated to
HIV-1 infection. The [cause of] death of one other subject, in 1987 [is
indeterminate, and the five other] recipients are still asymptomatic 14 to 18
years after infection and have not received antiretroviral therapy.” Wonder of
wonders. Likewise, in the July 1999 issue
of the Journal of Medical
Virology, Candotti et al’s study
of sixty eight ‘long term non-progressors’ mentioned coincidentally that none
were on “antiretroviral therapy”. This tallies with the observation of prominent
AIDS researcher Dr Jay Levy, Professor
of Medicine at the University of California at San Francisco, in the
Lancet in 1998 that “long-term survivors of HIV” have all avoided
‘antiretrovirals’. Similarly Dr
Donald Abrams, Professor of Medicine and director of the AIDS program at San
Francisco General Hospital, noticed in 1996: “I have a large population of
people who have chosen not to take any antiretrovirals... I’ve been following
them since the very beginning... They’ve watched all of their friends go on the
antiviral bandwagon and die.” In the same year and in the next, two papers in
the Journal of Infectious Diseases
took a formal look at the curious relationship between keeping off ‘antiretroviral
therapy’ and staying alive. Hogervorst et al noted that “None of the LTAs [long term asymptomatics]
received any antiviral drugs during the study; however, 3 [of 6] rapid
progressors…were treated with zidovudine…[and] a rapid progressor was treated
with didanosine during the study.” Montefiori et al found similarly: “LTNPs [Long-term non-progressors] were
defined as having documented HIV-1 infection for >7 years, CD4 cell counts
of >600 cells/cubic mm, and no symtpoms related to HIV-1 infection. With the
exception of [two of nineteen] patients, no patients had ever received
antiretroviral therapy.”
[41] In 1997, The
Canadian Pharmaceutical Association warned in its Compendium of Pharmaceuticals, “The long-term consequences of
in-utero and infant exposure to zidovudine are unknown. The long-term effects
of early or short-term use of zidovudine in pregnant women are also unknown.”
Likewise, the US Centers for Disease Control’s April 1998 Guidelines for the Use of Antiretroviral Agents in Pediatric HIV
Infection cautioned, “Data from clinical trials that address the
effectiveness of antiretroviral therapy in asymptomatic infants and children
with normal immune function are not available… The theoretical problems with
early therapy include the potential for short- and long-term adverse effects,
particularly for drugs being administered to infants aged <6 months, for
whom information on pharmacokinetics, drug dosing, and safety is limited…[and]
clinical trial data documenting therapeutic benefit from [antiretroviral
therapy] are not available.”
[42] However, in his paper
in AIDS in May 1999, Rapid disease progression in HIV-1
perinatally infected children born to mothers receiving zidovudine monotherapy
during pregnancy, Professor de Martino, Coordinator of the Italian Register
of HIV Infected Children at the Department of Paediatrics, University of
Florence in Italy reported that “Comparison of HIV-1-infected children whose
mothers were treated with ZDV with children whose mothers were not treated
showed that the former [AZT treated] group had a higher probability of
developing severe disease (57.3%…versus 37.2%)…or severe immune suppression
(53.9%…versus 37.5%…) and a lower survival [rate] (72.2%…versus 81.0%…).” De
Martino’s findings accorded with a report in 1996 by the American National
Institute of Child Health and Human Development regarding the clinical outcome
of AZT treatment of HIV-positive babies: “In contrast with anecdotal clinical
observations and other studies indicating that zidovudine favorably influences
weight-growth rates, our analysis suggests the opposite [and] our findings
suggest that the widely held view that antiretroviral treatment improves growth
in children with HIV disease needs further study.” In June 2000, De Souza et al published consistent findings in AIDS concerning the Effect of prenatal zidovudine on disease progression in perinatally
HIV-1-infected infants. Their objective was to “determine the influence of
prenatal zidovudine (ZDV) prophylaxis on the course of HIV- 1 infection in
children by comparing the clinical outcome of infants born to HIV-
1-seropositive mothers who did versus those who did not receive ZDV during
pregnancy. METHODS: Medical records of HIV-1-seropositive mothers and their
infants were reviewed retrospectively. Participants were divided according to
maternal ZDV use: no ZDV (n = 152); ZDV (n = 139). The main outcome measure was
rapid disease progression (RPD) in the infant, defined as occurrence of a
category C disease or AIDS-related death before 18 months of age. RESULTS: HIV
vertical transmission rates were significantly different (no ZDV versus ZDV: 22.3% versus 12.2%; p =
.034). Among infected infants, the RPD rate was 29.4% in the no ZDV group
compared with 70.6% in the ZDV group (p = .012), and prematurity was
significantly associated with a higher risk of RPD (p = .027). CONCLUSIONS: The
rate of RPD was significantly higher among perinatally infected infants born to
HIV-infected mothers treated with ZDV than among infected infants born to untreated
mothers…” The following month, in the July 2000 issue of the Journal of Infectious Diseases, Kuhn et al reported likewise in their study of 325 HIV-positive children
born between 1986 and 1997 until death or diagnosis with AIDS: Disease progression and
early viral dynamics in human immunodeficiency virus-infected children exposed
to zidovudine during prenatal and perinatal periods. Their findings were
summarised by Reuters Health: “Among
infected children who did not receive ART before AIDS diagnosis, 44% developed
AIDS or died before age 12 months when they were exposed to prenatal or
perinatal zidovudine. However, among HIV-infected infants not exposed to
zidovudine prophylaxis, rate of death or progression to AIDS was only 24%…
Zidovudine exposure before birth or perinatally appears to accelerate disease
progression in HIV-infected infants, but this can be counteracted by early
treatment with multidrug antiretroviral therapy (ART).” Blind to her own findings, and like De
Martino, Blanche, De Souza and pals, all AZT adherents to the end, Kuhn bubbled
to the reporter that AZT is “obviously and absolutely the primary thing that
must be done” to prevent ‘HIV transmission’ to infants. As long as you follow
up with more metabolic poisons: “The data showed that those receiving ART
subsequent to zidovudine prophylaxis were in fact not compromised in any way.”
She speculated that “more rapid disease progression in infants who become
infected despite zidovudine prophylaxis may be due to an as-yet-unidentified
factor in mothers.” As if AZT itself isn’t enough to do the trick. Karen Emmons
reported in similar vein in her jolly piece in the San Francisco Examiner on 31 May 1999, Thailand wins a round against HIV: “Of the children who were born
HIV-positive in Bangkok in the past four years and received the combination
drug treatment [AZT and ddI]…one-fourth died in their first year, about 33
percent by their second year, 40 percent by age 3, and then the mortality
tapered off.” This is a medical victory? On these data, a critical journalist
might have reported an iatrogenic drug disaster.
[43] That’s just what some observers think AIDS in the US
largely to have been, and if one looks at the CDC’s AIDS mortality figures read
against the frequency of AZT use there, it’s not hard to see why. AIDS deaths
trebled between 1988 and 1989 with the recommendation that AZT be given to
asymptomatic HIV-positives; they rose steadily by 1994/5 to fifteen times what
they had been prior to the introduction of AZT as an AIDS drug in 1986/7, and
then fell precipitously - by 1997 to less than half of the 1994/5 death rate
following the slashing of the recommended dose by two thirds, and the
abandonment of AZT-monotherapy in favour of ‘combination therapy’, still toxic
but not as immediately so. At the first meeting of President Mbeki’s
International AIDS Advisory Panel of orthodox and dissident AIDS experts
convened in Pretoria over 6 and 7 May 2000, Dr. Claus Koehnlein, a German physician
on the panel, told journalist Celia Farber, “I remember vividly the early
years, and seeing those AZT patients, and they just had no bone marrow left and
that was it …we killed a whole generation of AIDS patients with AZT. Especially
in the early high doses of 1200 and 1500 milligrams. That was just murder.” On
3 February 2000, in an article Experts
Warn Against Using AZT On Pregnant Women, the Inter Press Service reported
him making similar points at an AIDS conference in New Delhi, India: “Since AZT
can directly cause several of the 30 AIDS-indicator diseases which form the
basis for AIDS diagnoses in the U.S, it logically follows that AZT can cause
AIDS when administered to an asymptomatic HIV-positive individual... In his
experience, most HIV-positive patients who were placed on AZT rapidly suffered
immune-deficiency and developed symptoms which were commonly ascribed to AIDS.
And most of the cases he knew of resulted in death. Koehnlein described AZT as
a ‘highly toxic and worthless drug approved by the U.S Food and Drug
Administration on the basis of fraudulent research and which continues to be
promoted in spite of being responsible for tens of thousands of deaths’.” In
fact there was no argument about it when during the AIDS Advisory Panel’s deliberations
at the first meeting another panelist, pharmaceutical biochemist Dr David
Rasnick, said that AZT had “killed a lot of people.” He reported to our
amazement during a tea break, “That was quite openly stated and nobody
disagreed with it. I would put the figure at least tens of thousands killed, at
the doses they were giving people in the early years.” Pharmacologist Dr Andrew
Herxheimer, Emeritus Fellow of the Cochrane Centre in the UK and WHO advisor on
essential drugs for developing countries, was on the panel too, invited for his
expertise on drug toxicity. He told medical documentary producer Joan Shenton,
“I think zidovudine was never really evaluated properly and that its efficacy
has never been proved, but its toxicity certainly is important. And I think it
has killed a lot of people. Especially at the high doses. I personally think it
not worth using alone or in combination at all.” The peculiar part of it is
that having been found to be too poisonous and ineffective as a monotherapy for
adults by 1994, AZT should thereafter be commended as such for babies in utero. For people in ‘developing
countries’ like South Africa at any rate: On 30 January 1998, the CDC advised
in its Morbidity and Mortality Weekly
Report that “when considering treatment of pregnant women with HIV
infection, antiviral monotherapy is now considered suboptimal for treatment;
combination drug therapy is the current standard of care.” About which we’ll
chat in a moment.
[44] One would think that
this mountain of toxicity data would give pause to doctors plying the drug on
pregnant women, but apparently not in the debased scientific atmosphere of the
AIDS era. One wonders whether the First Precept of the Nuremberg Code -
informed consent - formulated after the Nazi medical experience, is ever
observed with such dangerous experimental treatment. Any bets on whether these
women are told, for instance, of Olivero et
al’s report in 1997 in the Journal of
Acquired Immune Deficiency Syndrome and Human Retrovirology bluntly headed AZT is a Genotoxic Transplacental Carcinogen
in Animal Models? The researchers reported that “In newborn monkeys and
mice, AZT was incorporated into DNA of many fetal tissues… AZT appears to be a moderately-strong
transplacental carcinogen… [and in] adult mice, lifetime AZT administration
induces vaginal tumors at a 10-20% incidence.” Or of the same researchers’
other paper in 1997 in the Journal of the
National Cancer Institute entitled Transplacental
effects of 3’-azido-2’,3’-dideoxythymidine: tumorigenicity in mice and
genotoxicity in mice and monkeys? In the light of earlier rodent studies
which found AZT “to be carcinogenic in adult mice after lifetime oral
administration”, the research team, all scientists with the US National Cancer
Institute, were concerned to assess “the transplacental
tumorigenic and genotoxic effects of AZT in the offspring of…mice and…monkeys
given AZT orally during pregnancy.” Pregnant mice and monkeys were given AZT in
the second halves of their gestational terms. After exposure to the drug in the
womb, the offspring of these animals were not further treated. By one year of
age, the mice exposed to AZT in utero “exhibited statistically significant,
dose-dependent increases in tumor incidence and tumor multiplicity in the
lungs, liver, and female reproductive organs. AZT incorporation into nuclear
and mitochondrial DNA was detected in multiple organs of transplacentally
exposed mice and monkeys. Shorter chromosomal telomeres were detected in liver
and brain tissues from most AZT-exposed newborn mice but not in tissues from
fetal monkeys.” The researchers concluded, “AZT is genotoxic in fetal mice and
monkeys and is a moderately strong transplacental carcinogen in mice examined
at 1 year of age. Careful long-term follow-up of AZT-exposed children would
seem to be appropriate.” Since “AZT is unequivocally a transplacental genotoxin
and carcinogen [and] given transplacentally to mice, benzopyrene produced lung
and liver tumour multiplicities similar to those observed [with AZT]”, the researchers
recorded their concern that “the current practice of treating HIV-positive
women and their infants with high doses of AZT could increase cancer risk in
the drug-exposed children when they reach young adulthood or middle age.”
[45] Following the
publication of these findings, GlaxoWellcome’s lawyers raced to hedge the
company against legal claims arising from the development of cancers in such
children, by amending its PRODUCT INFORMATION sheet under the section PRECAUTIONS: Information for Patients:
Carcinogenesis, Mutagenesis, Impairment of Fertility. On 4 March 1998, to
the sentence “The long-term consequences of in utero and infant exposure to
Retrovir are unknown” was added the phrase “including the possible risk of
cancer.” And the Olivero studies were deemed ominous enough to warrant mention
in a substantial new paragraph.
[46] But as AIDS journalist
Laurie Garrett reported in Newsday on
3 February 2000 (apparently quoting Kevin De Cock of the US Centres for Disease
Control), “Nobody is keeping track of the thousands of women and babies who
have received AZT or nevirapine to see what - if any - side effects might turn
up in the HIV-negative among them years after taking the drugs.”
[47] Nor does it seem very
likely that HIV-positive pregnant women will be told of Olivero et al’s
paper in AIDS in January 1999,
reporting the research of a major collaborative investigation by several
institutions in the US, overseen by the National Cancer Institute. In view of
the 1997 animal research findings mentioned above, the researchers were
concerned to establish whether their observations applied to humans, that is,
whether AZT administered to HIV-positive pregnant women was incorporated into
their DNA and that of their babies. It was found that it was. The ramifications
of this for the potential human carcinogenicity of AZT were conveyed in the
researchers’ recommendation that “the biologic significance of ZDV-DNA damage
and potential subsequent events, such as mutagenicity, should be further
investigated in large cohorts of HIV-positive individuals [because]…these data
raise the possibility that the presence of extensive ZDV incorporation into
human DNA may be cumulative, with potential long-term consequences such as
mutagenicity and tumorigenicity.” At the 1st National AIDS
Malignancy Conference held in the US in 1997, Olivero emphasised that
“pound-for-pound” the doses of AZT they gave to the animals were close to doses
given to HIV-positive pregnant women - in fact the monkeys were given less.
[48] And it
sure would be surprising were these women - advised to go on a bracing ‘short
course’ of AZT treatment - to be told about the findings reported in Mutation Research in July 1999: 3’-azido-3’-deoxythymidine transplacental
perfusion kinetics and DNA incorporation in normal human placentas in similar
terms perfused with AZT by Olivero and Poirier of the Laboratory of
Cellular Carcinogenesis and Tumor Promotion, US National Cancer Institute, and
Parikka and Vahakangas of the Department of Pharmacology and Toxicology,
University of Oulu, Finland. Concerned because “transplacental exposure studies
demonstrated that AZT is a moderate to strong transplacental carcinogen in mice
[and] the consequences of transplacental AZT exposure to the fetus remain
unknown”, the researchers investigated “the extent and kinetics of AZT transfer
across the human placenta.” They reported, “Since AZT crosses the human
placenta and becomes rapidly incorporated [within 2 hours of AZT perfusion]
into DNA of placental tissue in a dose-dependent fashion, [this suggests] that
even short exposures to this drug might induce fetal genotoxicity… In previous
studies AZT has been shown to produce both large-scale DNA damage and point
mutations. Skin tumors induced in mice by transplacental AZT initiation and
subsequent topical promotion had mutations in Ha-ras Exon I codons 12 and 13,
but these mutations were not observed in liver and lung tumors from mice given
the same exposure. The fact that the recommended treatment involves AZT use for
the last 6 months of pregnancy, suggest that human fetuses may also sustain
AZT-DNA damage… the consequences of any fetal exposure to a nucleoside analog,
in utero, remain unknown and a long-term
follow up of children prenatally exposed seems to be appropriate.” It certainly
would - in the light of Poirer et al’s new paper currently in press for
publication in the Journal of Acquired
Immune Deficiency Syndrome and Human Retrovirology in 2000:
Incorporation of 3’-azido-3’-deoxythymidine
(AZT) into fetal DNA, and fetal tissue distribution of drug, after infusion of
pregnant late-term rhesus macaques with a human- equivalent AZT dose.
And Diwan et al’s report in Toxic
Applied Pharmacology (Vol. 15) in 1999: Multiorgan
transplacental and neonatal carcinogenicity of 3’-azido-3’-dideoxythymidine in
mice.
[49]
Protagonists for the supply of AZT to HIV-positive pregnant women base their
fervent case on the finding that the babies of these women given AZT are less likely
to be born HIV-positive than those of mothers not so treated. In the popular
view, this evinces successful AZT interdiction of HIV transmission from mother
to child (on the fallacious assumption that the mere presence of antibodies
invariably signifies an active rather than a defeated infection). But since the
CDC reported in its Morbidity and
Mortality Weekly Report on 30 January 1998 that AZT causes “only a
minimal…reduction in maternal and antenatal HIV/RNA copy number”, i.e.
the ‘viral load’ in HIV-positive mothers, reduced levels of ‘HIV antibodies’
reportedly observed in the blood of infants exposed to AZT in utero
are better and more obviously explained in terms of AZT’s
broad cellular toxicity: In common with all chemotherapeutic agents, AZT is
particularly deadly to rapidly dividing cells like lymphocytes - which generate
antibodies. By inhibiting lymphocyte replication in mothers and their foetuses
or neonates, AZT reduces antibody production generally, thus giving rise to a
lower number of reactive ‘HIV antibody test kit’ results among neonates exposed
to AZT in the womb or after birth. As Separation Scientific’s manual for its DB
HIV Blot 2.2 antibody test tells us, “infants may test positive for HIV-1 due
to passive transfer of maternal antibodies which may persist for several
months” so anxiously testing them after birth with HIV antibody test kits is
perfectly futile. And you can’t properly use PCR tests ‘to test for the virus
itself’ as one sometimes hears, because the manual for the only such test
licensed by the FDA for use in clinical practice, the Roche Amplicor HIV-1
Monitor Test (for measuring‘viral load’) warns that it is “not intended to be
used as a screening test for HIV-1 or as a diagnostic test to confirm the
presence of HIV-1 infection.” As for
so-called qualitative PCR HIV tests, they are so notoriously non-specific that
Roche admonishes that its Amplicor HIV-1 Test, a ‘qualitative assay’, is “For
research use only. Not for use in diagnostic procedures.” In the Practising
Midwife in 1999, Chrystie
confirmed in an article Screening of
pregnant women: the case against that “Those laboratories which undertake
HIV screening and confirmation assays understand fully the technical problems
associated with PCR and other amplification assays and it is precisely for
those reasons that PCR is NOT used as a confirmatory assay (as discussions with
any competent virologist would have informed them).” Rich et al reported Misdiagnosis
of HIV infection by HIV-1 plasma viral load testing: A case series in Annals
of Internal Medicine in 1999:
“Plasma viral [RNA] load tests were neither developed nor evaluated for the
diagnosis of HIV infection…Their performance in patients who are not infected
with HIV is unknown.” The text-book excuse for this is contamination, but An
AIDS Case in the appendices to this
debate reveals much more challenging problems with ‘HIV-PCR testing’. One day
it will occur to some bright young doctor to test babies born to HIV-negative
mothers for ‘HIV antibodies’. Or a group of spinsters in a poor rural reserve.
Or underfed prepubescent children there. He or she is likely to be in for a
shock at how many are HIV-positive. And that might serve as a spur to a long
overdue re-examination of the real meaning of reactive ‘HIV antibody’ test
results. But that’s a scandal on which we had best not get started in this
discussion of AZT. Whatever ‘HIV-positive’ actually signifies, one can only
wonder at doctors’ eagerness to feed this poison to HIV-positive pregnant women
in the light of Semba et al’s study of the effects of Vitamin A
administration to such women, published in 1993 in Archives of Internal
Medicine. Mothers given Vitamin A had less
HIV-positive babies than the control group, and the results were better than
those achieved in the Connor AZT study, ACTG 076 published a year later in
the New England Journal of Medicine. But
then Western medicine has always been partial to the violent option. Or maybe
it’s just that there’s no role for doctors or money to be made from providing
food-aid and vitamins to the poor.
[50] The dangers of AZT for babies and neonates have
fallen on deaf ears at the Perinatal AIDS Unit of the Chris Hani-Baragwanath
Hospital in Johannesburg. Dr James McIntyre dismissed this critique thus: “I
have read the piece with interest, although little agreement with your
arguments (sic).” Which I suppose is
why he felt no compunction about pitching for AZT (for a pleasing fee no doubt)
from the pulpit of an awesome temple - pillars and everything - set up by
GlaxoWellcome in the centre of the Exhibition Hall at the Durban AIDS
Conference on 10 July 2000. Despite Mbeki’s cautionary message about AZT in
October 1999, paediatrician Dr David Johnson gushed on television two months
later, “When used for mother to child transmission, it’s an absolute lifesaver.
It saves, has the potential to save millions and millions of babies.” But Dr
Glenda Gray, director of the unit, takes the cake. She told the Washington
Post on 16 May 2000, “If they’re
not going to provide us with AZT then the best thing that the government can do
is to ask us to strangle them all at birth.” The kind of remark one might
expect from someone whom I watched covering her mouth and giggling like a
school-girl, uncomprehending as Professor Manu Kothari from Seth Gordhandas
Sunderdas Medical College, King Edward Memorial Hospital, Mumbai, India addressed the second meeting of the AIDS Advisory
Panel and bestowed it with insights of the most rousing profundity.
[51] We seem to be face to face with a replay of the
Diethylstilbestrol debacle, but far worse. A synthetic oestrogen-like hormone,
DES was heartily prescribed to pregnant women “for routine prophylaxis in ALL
pregnancies... 96 per cent live delivery with desPLEX in one series of 1200
patients - bigger and stronger babies, too. No gastric or other side effects
with desPLEX - in either high or low dosage.” So puffed a typical advertisement
in a medical journal in 1957:
To quote Nora Cody speaking
in Bethesda, US at the National DES
Research Conference in July 1999, “30 years ago today DES was still being
prescribed to pregnant women in this country and, indeed, around the world. By
1969 scientists had studied this scientific substance for over three decades.
Over and over, they had found cancer in laboratory animals. In the famous
Dieckmann study in 1953, they had discovered that DES was completely
ineffective in preventing miscarriage and in fact more harmful than a placebo.
Yet for all of this scientific inquiry, there was a fundamental failure, and
DES showed us the terrible potential for human tragedy from scientific
discovery.” Hundreds of thousands of people were exposed to DES in utero,
leading to a variety of
adverse health consequences especially among women. These included an elevated
risk of developing clear cell adenocarcinoma of the vagina or cervix (a rare
cancer virtually non-existent in non-exposed women of similar age), an
increased incidence of structural changes in their reproductive organs (virilisation),
an increased risk for infertility, and a higher risk for ectopic pregnancy,
miscarriage, and preterm labor and delivery. New York attorney Ron Benjamin,
specialising in toxic torts and defective drug liability, told me over the
telephone in May 2000 that he had recently pulled $13m from a jury in a DES
injury case he had handled. I predict an avalanche of claims against
GlaxoWellcome arising from AZT poisoning that will prove as uncontainable as
the run of asbestosis claims which nearly brought down Lloyds of London – as
reported in Time in February 2000.
[52] Reporting to the US Surgeon General in 1970, the Ad
Hoc Committee on the Evaluation of Low Levels of Environmental Chemical
Carcinogens recommended that “Any substance which is shown conclusively to
cause tumors in animals should be considered carcinogenic and therefore a
potential cancer hazard for man… No level of exposure to a chemical carcinogen
should be considered toxicologically insignificant for man. For carcinogenic
agents a ‘safe level for man’ cannot be established by application of our
present knowledge...” Have the rules changed? Is AZT too big to ban -
under the Delaney Amendment outlawing
potentially carcinogenic drugs in the US? Or are the rules about exposing
patients to likely carcinogens just relaxed a bit when they are female and
pregnant? Or black or gay?
[53] For those of us who
like to trust that medical experts in high places know what they are doing and
think straight, the following statement by Dr. Ellen Cooper, Principal
Researcher of the Women and Infants Transmission Study in the US, might come as
a bit of a shock. Quoted in Mothering
magazine in September/October 1998, she said, “We don’t know what the long-term
effects of AZT use during pregnancy might be, but so far we have seen virtually
no adverse effects in the short term... Not one single tumor. Not one... I mean
[the children] have cancers, lymphomas, and other problems like that...but
there’s no reason to link those cancers to AZT.” Her reticence about coming to
terms with the horror she helped spawn makes sense, seeing that she was a
director of the FDA on the panel that approved AZT.
[54] The
likely carcinogenicity of AZT, demonstrated by recent studies, is actually no
news at all. Way back in December 1986, a review of numerous AZT studies
entitled Review & Evaluation of
Pharmacology & Toxicology Data was submitted to the US Food and Drug
Administration by its in-house toxicology analyst Dr Harvey Chernov. He
reported - apart from the observation that AZT was toxic to bone marrow and
caused anaemia in all species of experimental animal, and humans too - that AZT
“was found weakly mutagenic in vitro in the mouse lymphoma cell system.
Dose-related chromosome damage was observed in an in vitro cytogenetic
assay using human lymphocytes”, and AZT was
found to be active in the Cell Transformation Assay, a stock test for
carcinogenic potential. He emphasised, “This BALB/c-3T3 neoplastic
transformation assay was performed according to standard operating procedure.
Concentrations
of AZT as low as 0.1 mcg/ml reduced the number of cells in culture after a
3-day exposure. A statistically significant increase in the number of aberrant
‘foci’ was noted at concentration of 0.5 mcg/ml. This behaviour is
characteristic of tumor cells and suggests that AZT may be a potential
carcinogen. It appears to be at least as active as the positive control
material, methylcholanthrene.” As Chernov explains it, “A test chemical which
induces a positive response in the Cell Transformation Assay is presumed to be
a potential carcinogen.” Naturally he advised the FDA against approving AZT,
but his report was buried. Indeed, it had to be flushed out of the FDA’s files
by resort to the machinery of the federal Freedom of Information Act some years
later. In 1994, in Cancer Research,
Olivero et al published more
AZT-rodent carcinogenicity findings: Vaginal
epithelial DNA damage and expression of preneoplastic markers in mice during
chronic dosing with tumorigenic levels of 3'-azido-2',3'-dideoxythymidine (AZT):
“…we have found positive correlations
between the dose of AZT administered to female CD-1 mice, the incorporation of
AZT into vaginal DNA, the hyperproliferation of the vaginal epithelial basal
layer, and the aberrant expression of alpha-6 integrin toward the epithelial
suprabasal strata of the vagina, a target organ for carcinogenesis in mice.
These results suggest that there is an ordered progression of abnormal events
leading to tumorigenesis in vaginal epithelial tissues.”
[55] Chernov’s bleak
predictions for the human carcinogenicity of AZT have since come true. But
you’d never know it reading the tortured spin of AZT promoters Broder et al
in their piece, Clinical Pharmacology of 3'-Dideoxythymidine
and Related Dideoxynucleosides, published in the New England Journal of
Medicine in 1989. Conceding that “it is of
particular concern that the drug may be carcinogenic or mutagenic” and “its
long term effects are unknown”, the authors state, “zidovudine may be
associated with a higher incidence of cancers in patients whose
immunosurveillance mechanisms are disturbed simply because it increases their
longevity.” Just muse on that as a vignette illustrating the quality of
reasoning exhibited by AIDS scientists, and then before you dry your eyes,
consider this - from the same illustrious peer-reviewed journal: In 1988, in
their paper Effect of
continuous intravenous infusion of zidovudine (AZT) in children with
symptomatic HIV infection, Pizzo et al claimed that AZT boosted the IQ of
twenty one HIV-positive children by fifteen points. “Transfusion was required
in 14 patients because of low levels of hemoglobin. Dose-limiting neutropenia
occurred in most patients who received doses of 1.4 mg per kilogram per hour or
more… Regardless of the starting dose, nearly all patients had a transient drop
in their neutrophil counts within 10 days of the initiation of AZT therapy… The
major limitation of the therapy was hematologic toxicity both the hemoglobin
concentration and the white-cell count… In three of the five children who died,
evidence of a response to AZT, particularly neurodevelopmental improvement, was
present at the time of death.” In declaiming these AZT-boosted
“neurodevelopmental” improvements, the excited researchers had the decency at
least to mention that the kids made brainy by AZT also happened to die. But not
Burroughs Wellcome, which seized on and punted this garbage as a selling hook
for AZT when advertising it in the Lancet:
“Helping keep HIV disease at bay in children. Generally well tolerated;
Improved cognitive function…”
[56]
Actually, AZT doesn’t make you clever, it makes you stupid. You may have heard
of ‘AIDS-dementia’. It’s like ‘neuro-syphilis’ - which no one gets anymore, now
that penicillin has taken over from arsenic and mercury salts to kill syphilis
spirochaetes. (The Oxford Companion to
Medicine admits, “…nearly all the late symptoms of syphilis were really due
to mercury poisoning.”) To be told by a doctor that you’re about to die would
knock the best of us off the psychological rails. Certainly I’ve seen this in
three AIDS-based cases I’m conducting. At the least of it, the diagnosis per se
can precipitate a health
collapse, as a glance at Ader, Felten and Cohen’s text, Psychoneuroimmunology
reveals. And the widow of my colleague killed
by AZT can confirm. Bacellar et al
reported in the journal Neurology in
1994 that “the risk of developing HIV dementia among those reporting any
antiretroviral use (AZT, ddI, ddC, or d4T) was 97% higher than among those not
using this antiretroviral therapy… In addition, the findings of our analysis
seem to confirm previous observation of a neurotoxic effect of antiretroviral
agents…linked…to the development of toxic sensory neuropathies, usually in a
dose-response fashion.” Remember the sensory and mental disturbances mentioned
above on the package blurb as being among AZT’s ‘side effects’? You know, the
ones caused by the poisoning of your nerves and brain? Which caused a client of
mine, among other unpleasant things, to lose his sense of taste. Heald et al
mentioned some of them in their
paper in AIDS in 1998, Taste and smell complaints in HIV-infected
patients. In a discussion of mitochondrial myopathy, Robbin’s Pathologic Basis
of Disease mentions
mitochondrial encephalomyopathy. The Concise
Oxford Medical Dictionary tells us that encephalomyopathy is “extensive
destruction of nerve cells throughout the nervous system [causing] widespread
disease of brain and spinal cord.”
[57] In the May 1999 issue
of Clinical Infectious Diseases, Fichtenbaum
et al at the Washington University
School of Medicine described the cases of three patients who developed
progressive multifocal leukoencephalopathy after four to eleven months of
HAART. Despite a change in their treatment, the research team “observed no
improvement [in two of the cases]… Neurologic deterioration continued, and
[the] patients died within 2 months.” They concluded that the condition can
“develop while using HAART” notwithstanding test results suggesting “a good
virologic response to antiretroviral therapy.” That the drugs themselves caused
the brain and neurological damage, they didn’t consider. Apparently Fichtenbaum
and his portly pals found the logical leap too wide to hazard. But not Research
Initiative Treatment Action in
their piece headed Just Sweat it Out:
Physical therapy’s role in the HIV pandemic under the chapter The Nervous
System and Physical Therapy:
“Peripheral neuropathy pain, which occurs in 40 to 60% of people with AIDS, is
one of the most common causes for referral to physical therapy and is often one
of the most neglected. Symptoms of peripheral neuropathy include burning,
numbness, and/or a tingling sensation of the extremities. Lower extremity
involvement is more common than upper extremity involvement. Problems with
ambulation, balance, and compensatory low back pain are also commonly
associated with peripheral neuropathy.” Since there isn’t a jot of evidence
that HIV attacks nerve cells, but ample evidence that nucleoside analogues like
AZT, 3TC, d4T, ddI and ddC do, the article concedes that “peripheral neuropathy
may be directly related to [such] pharmacological agents…”
[58] If it’s not good for
your head, AZT is not great for your heart either. Lipshultz pointed out in the
New England Journal of Medicine in 1998
that “possible mechanisms [for heart muscle disease among HIV-positive
patients] include cardiotoxicity as a result of antiretroviral therapy...” And
in their paper in Nature Medicine in
1995, Mitochondrial toxicity of antiviral
drugs, Lewis and Dalakas mention heart disease among the many
manifestations of drug toxicity caused by ‘antiviral’ nucleoside analogues
(ANAs) like AZT, noting that “the prevalent and at times serious ANA
mitochondrial toxic side effects are particularly broad ranging with respect to
their tissue target and mechanisms of toxicity: Haematalogical; Myopathy;
Cardiotoxicity; Hepatic toxicity; Peripheral neuropathy.” On 24 February 2000,
in a report Zidovudine causes
cardiomyopathy in animal model,
Reuters Health mentioned Lewis et al’s
rodent study findings that “Pathological changes occurred in the hearts of all
the animals following 35 days of AZT treatment”, namely the “structural and
functional changes of mitochondrial cardiomyopathy.” Nothing new. In 1992 in
Annals of Internal Medicine Herskowitz et al published
Cardiomyopathy Associated with Antiretroviral Therapy in Patients with
HIV Infection: A Report of Six Cases: “Symptomatic congestive heart failure
has been described as part of the spectrum of human immunodeficiency virus
(HIV)-related cardiac disease [but] studies have failed to show HIV genomic
material in endomycocardial biopsy samples taken from patients with
HIV-associated mycocarditis and clinically established congestive heart
failure. Other etiologies should be considered, such as drug-induced
cardiotoxicity, as suggested by the recent finding of zidovudine-induced
cardiomyopathy in rats and zidovudine-induced skeletal myopathy in humans.”
Lewis et al confirmed Herskowitz’s
apprehensions in Circulation Research
two years later, their findings summed up in the title: Cardiac Mitochondrial
DNA Polymerase-y Is Inhibited Competitively and
Noncompetitively by Phosphorylated Zidovudine. In the August 2000 issue
of European Journal of Medical Research,
Rickerts et al investigated the Incidence of myocardial infarctions in
HIV-infected patients between 1983 and 1998: the Frankfurt HIV-cohort study
and found “The incidence of MI in HIV
infected patients increased in our cohort after the introduction of HAART.” In
the same month, in the International
Journal of STD & AIDS, Koppel et
al reported “A significant number of the HAART patients had very high
levels of Lp(a) and various combinations of increased lipid values associated
with considerably increased risk for CHD [coronary heart disease]. The
elevation of Lp(a) did not relate to any other clinical or laboratory parameter
than to LDL-cholesterol.” On the other hand, in September 2000, the New
England Journal of Medicine
published a study by Lipshultz et al.
Reuters reported: “New tests of the GlaxoWellcome AIDS drug
AZT show that, unlike infant monkeys exposed to the drug, it does not damage
the heart of human newborns… The drug… had been shown to cause some heart
abnormalities in infant monkeys whose mothers had been exposed to it while
pregnant. Studies in children have produced mixed results.” The study involving
185 babies found that, “infants born to HIV-infected women and exposed to
zidovudine were no more likely to have abnormal [hearts]...than were infants
who did not have zidovudine treatment.” Of course, biopsies of cardiac tissue
weren’t taken to determine whether it had suffered the same kind of damage seen
in adults and in animal studies. The children’s hearts were not conspicuously
harmed. Which is not saying very much. Especially since cardiomyopathy was one
of the abnormalities in AZT-exposed babies reported by Blanche et al in
the Lancet in September 1999. But the curious thing about the Lipshultz
report is the wide press it enjoyed in the newspapers and in discussion forums
on the internet, unlike a host of other recent negative findings about AZT. As
if it decisively vindicated AZT from the dense surrounding countryside of
papers returning adverse data.
[59] It would appear that
AZT and chemically related drugs can blind you too. In the Journal of Infectious
Diseases in March 1999, Karavellas and Plumm reported their investigation of
“the likelihood of the development of a new ocular inflammatory syndrome
(immune recovery vitritis, IRV), which causes vision loss in AIDS patients with
cytomegalovirus (CMV) retinitis, who respond to HAART. We followed 30
HAART-responders with CD4 cell counts of >/=60 cells/mm3. Patients were
diagnosed with IRV if they developed symptomatic vitritis of >/=1+ severity
associated with inactive CMV retinitis. Symptomatic IRV developed in 19 (63%)
of 30 patients…over a median follow-up from HAART response of 13.5 months…
These data suggest that IRV develops in a significant number of
HAART-responders with CMV retinitis...” It’s amazing. Some ‘successfully’
treated AIDS patients go blind. A brand-new disease construct comes into being:
‘Immune Recovery Vitritis’. Roche hawks its ‘anti-CMV medication’, with
advertising directed specifically at gay men whose sight has been wrecked by drug
damage to their ocular nerves. In an echo of the Japanese Clioquinol disaster,
cytomegalovirus is blamed for the blindness, not the HAART drugs,
notwithstanding their well-established neuro-toxicity.
[60] During a polio-like
epidemic in the sixties in Japan, Subacute Myelo-Optico-Neuropathy or SMON
caused blindness, paralysis and death in thousands of cases. The Japanese
medical research establishment approached the crisis on the footing that some
new unknown infectious agent was responsible. Echo-, Coxsackie- and
lenti-viruses were put in the dock in turn. Professor Shigeyuki Inoue at Kyoto
University’s Institute for Virus Research claimed that a virus he had
identified (coincidentally in the same herpes-class as the common-place and
generally harmless cytomegalovirus) was the cause of SMON, and it was accepted
as such in the 1974 edition of the American textbook, Review of Medical
Microbiology. With modern medicine’s bias to
germs as the causes of disease, entirely overlooked was the possibility that the
epidemic was caused not by a contagion but by a toxin - until the
epidemiological anomalies became uncontainable for the viral culprit theory.
Finally, an anti-diarrhoereal drug, Entero-Viaform containing Clioquinol was
found to be the cause. Inadequately tested, it turned out to be neuro-toxic.
When it was banned, the plague ceased, and in the litigation that followed its
manufacturer Ceiba-Geigy was taken to the cleaners.
[61] But back to cancer. Pluda
and colleagues, all researchers with the US National Cancer Institute, no less,
reported in 1990 in Annals of Internal
Medicine that on AZT, your chances of developing lymphoma relative to the
rest of the population went up 50 fold: “The estimated probability of
developing [Non-Hodgkins] lymphoma [in patients taking AZT alone, or in
combination] by 30 months of therapy was 28.6% and by 36 months, 46.4%.” The
authors considered “a direct role of therapy itself” for the development of the
disease, and warned, “Zidovudine can act as a mutagen.” On 20 July 2000
Associated Press released a piece by
Emma Ross entitled AIDS Treatments
Studied, mentioning a Danish research report in the same month in the Lancet.
Examining the cases of 7300
European HIV patients, she said the study (by Ludgren et al) had found that the
percentage contracting “non-Hodgkins
lymphoma had quadrupled since the [HAART] drugs were introduced six years ago.”
Of course the rest of her story had a different spin, but it is the data, not opinions,
that count.
[62] In the light of these reports, is it truthful for
AZT manufacturer GlaxoWellcome to persist with the assertion, as it does in its
AZT package insert that, “It is not known how predictive the results of rodent
carcinogenicity studies may be for humans”? After all, “At doses that produced
tumors in mice and rats, the estimated drug exposure [for mice] …was [only
about] 3 times…the estimated human exposure at the recommended therapeutic dose
of 100 mg every 4 hours.” And how frank is GlaxoWellcome in disposing of
Chernov’s positive Cell Transformation Assay findings with the bald
unelaborated statement in the same package insert, “In an in vitro mammalian cell transformation assay, zidovudine was
positive at concentrations of 0.5 µg/ml and higher”? How many doctors, let
alone patients, appreciate from this that as little as half a millionth of a
gram per millilitre of AZT came up positive in a standard drug-industry
screening-test for potential drug carcinogenicity? And what risks for patients
this portends?
[63] In AIDS in May 1999, Grulich et
al reported a 16-year study of cancer incidence among people given an AIDS
diagnosis in New South Wales, Australia. The researchers noted that among more
than 3600 AIDS diagnoses, fully one quarter of the patients had developed
cancers including those of lung, skin and lip, leukaemia and Hodgkins Disease -
none of which are ‘AIDS indicator diseases’. “There was an increased incidence
of several other forms of cancer, some of which are known to occur at increased
rates in transplant recipients who have received immunosuppressive therapy.”
Presumably these patients had been dosed according to the standard
‘antiretroviral’ treatment protocol - AZT alone or in combination with related
drugs. All of which, like ‘immunosuppressive therapy’, are destructive of the
cells of the immune system. They observed: “The incidence of Hodgkin’s Disease
increased significantly at the time of AIDS diagnosis.” Since the disease sets
in after the diagnosis is made and the treatment begins, the sensible doctor
might wonder about the medicine. Such enquiry might be stimulated by Zietz
et al’s paper in June 1999 in the New England Journal of Medicine
reporting An unusual cluster of cases of
Castleman's disease during highly active antiretroviral therapy for AIDS.
Most patients with this “rare… lymphatic hyperplasia…disease” typically present
with “multicentric lymphadenopathy… an interfollicular predominance of plasma
cells… and progressive systemic symptoms or with a more localized, indolent
disease that can often be cured by local excision.” In the four cases reported,
the patients suffered “Fever, weakness, generalized enlargement of lymph nodes,
and marked polyclonal gammopathy… [and three] died within a week after the diagnosis.”
Speculating about the possible causes - the virus HHV-8 is tentatively mooted -
the authors note that in all cases “symptoms of multicentric Castleman’s
disease started after the initiation of highly active antiretroviral therapy…”
Sure they did. Just as Simone et al
reported in Annals of Internal Medicine
in September 2000: Inflammatory Reactions
in HIV-1-Infected Persons after Initiation of Highly Active Antiretroviral
Therapy: “Inflammatory reactions involving opportunistic infections,
AIDS-associated malignant conditions, and other noninfectious diseases have
recently been described in patients infected with HIV-1. These conditions often
appeared shortly after the introduction of HAART and were associated with
pronounced reductions in plasma HIV-1 viral load and increases in CD4(+)
T-lymphocyte counts.” In other words the drugs seem to fix your symptomless HIV
but make you very sick. Only in the AIDS age!
[64] In October 1998, at a
conference in the US sponsored by the World Health Organization, experts from
all over the world convened under the aegis of the International Agency for
Research on Cancer to examine the potential carcinogenicity of AZT. At the end
of their colloquium, AZT was classified a “possible human carcinogen.” The
panel would doubtlessly have put it less tentatively had many of the most
significant research reports on AZT-carcinogenicity mentioned in this review
been published before the conference and not after it. Like this one:
[65] In February 1999,
researchers with the National Toxicology Program of the Department of Health
and Human Services in the US delivered a report entitled TR-469 Toxicology and Carcinogenesis Studies of AZT (CAS No.
30516-87-1) and AZT/a-Interferon
A/D B6C3F1 Mice (Gavage Studies). They concluded, “Under the conditions of
these 2-year gavage [oral force feeding] studies there was equivocal evidence
of carcinogenic activity of AZT in male mice based on increased incidences of
renal tubule and harderian gland neoplasms in groups receiving AZT alone. There
was clear evidence of carcinogenic activity of AZT in female mice based on
increased incidences of squamous cell neoplasms of the vagina in groups that
received AZT alone or in combination with -interferon A/D. Hematotoxicity
occurred in all groups that received AZT. Treatment with AZT alone and AZT in
combination with -interferon A/D resulted in increased incidences of epithelial
hyperplasia of the vagina in all dosed groups of females.” Under the heading
GENETIC TOXICOLOGY, the investigators reported, “AZT is mutagenic in vitro
and in vivo. It induced gene mutations in Salmonella typhimurium strain
TA102. AZT induced sister chromatid exchanges in cultured Chinese hamster ovary
cells. In vivo studies with male mice
administered AZT by gavage showed highly significant increases in
micronucleated erythrocytes in bone marrow and peripheral blood after exposure
periods that ranged from 72 hours to 14 weeks.” How many studies will it take?
[66] Debunking Martin’s
claims as to the efficacy of AZT for “post-exposure prophylaxis” would take
more space than the joke warrants. Put it this way. There are no smart-bomb
drugs for viruses, especially retroviruses like HIV, claimed by ‘AIDS experts’
not merely to infect our cells but to actually get into our DNA. As Nobel
laureate retrovirologist and former director of the US National Institutes of
Health, Dr. Harold Varmus put it in June 1998, “Trying to rid the body of a
virus whose genome is incorporated into the host genome may be impossible.” Any
honest, competent GP will tell you that viruses are beyond medicine’s reach.
With viral diseases you take it easy and hope for the best. Presuming of course
you have the disease you’ve been told you do, but just what HIV antibody test
results really tell is another story, and what an unbelievable scientific
shambles it is. In its PRODUCT INFORMATION advisory, GlaxoWellcome says about
claims for AZT as a preventative drug for “post-exposure prophylaxis”:
“Patients should be advised that therapy with Retrovir has not been shown to
reduce the risk of transmission of HIV to others through sexual contact or
blood contamination.” In their paper in AIDS
in August 2000, Post-exposure prophylaxis
with highly active antiretroviral therapy could not protect macaques from
infection with SIV/HIV chimera, Le Grand et al pointed out that, “To
date, only one study has reported that
zidovudine (ZDV) alone may protect from occupational post-exposure infection
with an efficacy estimated at 81%. [Cardo et
al of the Centers for Disease
Control and Prevention Needlestick Surveillance Group: A case-control study of
HIV seroconversion in health care workers after
percutaneous exposure in New England
Journal of Medicine 1997.] However, a retrospective case-control study is
not the optimal design for assessing the efficacy of such strategies, thus
limiting the significance of this observation.” In their experiment on macaques
monkeys to determine the efficacy of post exposure prophylaxis following
deliberate infection, they found that it didn’t work: “This is the first
demonstration that post-exposure prophylaxis of HIV transmission with a
therapeutic design recommended in humans could not protect macaques from
experimental challenge with a pathogenic lentivirus closely related to HIV-1.”
[67] Overlooked by just
about everyone is a fundamental biochemical reason why AZT can never in
principle be a prophylactic agent to prevent HIV infection. It is rudimentary
that HIV is a retrovirus, so the experts tell us. And that retroviruses have
RNA not DNA at their core. RNA differs from DNA in that in place of thymidine,
it has uracil as one of its nucleotides. AZT, (a fake thymidine stand-in) is
claimed by the experts to disrupt the formation of proviral DNA by substituting
itself in place of natural thymidine. But only after it has infected the cell
does the process start, the ‘AID