THE TROUBLE WITH NEVIRAPINE
By Anthony Brink
April 2002
I could not stop something I knew was wrong and
terrible.
I had an awful sense of powerlessness.
-- Andrei Sakharov
This article is divided into four parts:
Part One relates the history and licensing of nevirapine in the
US and Europe, and outlines its pharmacology and its toxicities;
Part Two reveals the extraordinary
circumstances in which the drug was licensed in Canada;
Part Three looks at a South African
clinical drug trial involving nevirapine and other drugs, aborted by
order of the Medicines Control Council in April 2001 after a spate
of severe toxic reactions, several fatal; Part
Four provides a critique for non-expert readers of HIVNET 012,
the Ugandan study of the effect of administering nevirapine to
HIV-positive pregnant women conducted by Guay et al, on the basis of
which the Treatment Action Campaign won an order from the High Court
on 15 December 2001 compelling the South African government to
supply the drug to such women and their newborn children. Appended
to this article are summary back-cover blurbs from the author’s
books, Debating AZT: Mbeki and the AIDS drug controversy and Just
say yes, Mr President: Mbeki and AIDS (in preparation for imminent
publication), reviews of the former, and an extract from the preface
to the latter concerning the professional South African AIDS-drug
lobby, the Treatment Action Campaign.
Part One
Take nothing on its looks; take everything on
the evidence, Pip; there is no better rule.
-- Charles Dickens, Jaggers the solicitor
in Great Expectations
Nevirapine, the manufacturer tells us, is a "non-nucleoside
analog reverse transcriptase inhibitor." It prevents "viral
replication" by binding "directly to the HIV RT enzyme", thereby
disrupting its ability to foster the formation of viral DNA. In
other words it clogs reverse transcriptase a bit like spilt crude
oil does penguins. But at a specific site. Like the bird’s head
only.
Or think of the enzyme being like a bricklayer laying DNA
building blocks. Nevirapine handcuffs his hands. Drugs in the AZT
class, similarly described, but without the "non-" prefix, are also
said to inhibit reverse transcriptase. But indirectly, like useless
straw bricks slipping into the place of clay ones, to prevent the
wall going up. So the theories go.
Let’s close our eyes and pretend just for now that reverse
transcriptase has unambiguously been shown to exist as a distinct
enzyme unique to retroviruses and not also a component of uninfected
human cells, and that retroviruses exist outside textbooks, like
Coffin’s, and children’s imaginations, as in the Superman cartoon
movie Cold Vengeance: "a Roscoe’s retrovirus…100 per cent
fatal", and that retroviruses can be malevolent and have sufficient
genetic complexity for the execution of their nefarious intentions,
and that HIV is one of them. Killing off our CD4 immune cells. No
evidence for that? OK, not attacking them directly, but hypnotising
them into committing suicide. Even those they haven’t been anywhere
near. Like telepathically. They call it "programmed cell-death." For
‘AIDS sufferers’ with sky-high CD4 cell counts, we’ll think up an
explanation another day. Likewise one for folks in peak health with
cell counts at rock bottom. Who should be gasping in hospices.
Overcome by opportunistic infections. Except that we’re talking
about some US Olympic athletes. HIV sits dormant in our cells, a
lurking lentivirus, poised to jump out and attack us after about a
decade or so. No, no, we’ve dumped that theory; the new one is that
it replicates from the start, incredibly rapidly but being
neutralised by antibodies, although not quite efficiently enough to
avoid being eventually overrun. Actually that model is now in the
toilet too, so we ‘AIDS experts’ are not too sure what to say
anymore, but who wants to get bogged down by details when we’ve got
to get out there and save lives? I mean let’s keep our eye on the
bigger picture. Because like hey, people are dying.
Nevirapine was first mooted as a potential new hi-tech anti-HIV
agent at the start of the ‘90’s. In Impure Science: AIDS,
Activism and the Politics of Knowledge, sociology Professor
Steven Epstein tells us that, "The second generation of antiviral
AIDS drugs – the non-nucleoside reverse transcriptase inhibitors
that had looked so promising in vitro – performed poorly in clinical
trials." This news was "nothing short of shattering" to guys like
Theo Smart of ACT UP New York, sister to our own Treatment Action
Campaign – massive expectations for it having been pumped up by
manufacturer Boehringer Ingelheim and its surrogates in AIDS
activist organisations across the country. Former history professor
Elinor Burkett picks up the trail in The Gravest Show on Earth:
America in the Age of AIDS: In February 1993, a first year
medical student at Harvard, Yung-Kang Chow, tooled around with the
flop drug, mixing it with the older ones, AZT and ddI. The test tube
action he claimed to have seen was packaged in a twelve-page press
release by the Harvard Medical School as the next thing: a likely
cure for AIDS. The New York Times, the television stations,
and everybody else fell for it. Never mind that Chow was light on
proof. The nevirapine combo idea got its next big boost from a
splash in Nature later that month. With all the hype and
hullabaloo, a large-scale clinical trial of this novel drug
combination approach was set up in the US over sixteen centres. But
after the 7th International AIDS Conference in Berlin was
over and English and American researchers got back to look at Chow’s
magical findings, and did a few experiments of their own, they
couldn’t replicate his results. So they started complaining. Chow’s
supervisor, top ‘AIDS expert’ Martin Hirsch, took another look at
Chow’s original research. It was a cock-up, he announced. Chow had
made a fundamental blunder vitiating his conclusions. Dreadfully
sorry, everyone. All the newspapers that had written about
nevirapine with such excitement in February and March now rained
tomatoes on it. Along with Nature, which published a
disavowal in July.
Now you might imagine that a formal concession that the root
study on the basis of which the drug went to clinical trials was
invalid would be cause to call off the trials. Because mirth had
taken the place of the model for the novel treatment approach. After
all, humans were being treated with a very poisonous chemical (we’ll
see below) for which there was no in vitro warrant, no
evidence of any efficacy – no matter how ingeniously this smart drug
had been engineered. According to a design brief like all good
engineering projects. Assumed sound. One of its parameters being
that reverse transcriptase is that distinct stuff mentioned earlier
– and part of the tiny foe perpetrating the crimes, all likewise
described. So it would be a big mistake to think we’re just going to
dump it after all that time and trouble. After all that money
invested in producing it, and all those high hopes of making so much
more. No way.
On completion of the clinical trials, this is what the
investigators reported: (i) Combined with AZT and ddI in patients
who’d taken antiretrovirals before, "nevirapine produced a sustained
improvement in CD4 count when compared with ZDV [AZT] plus ddI."
(The fact that CD4 cell counting as a surrogate marker for clinical
health had been discredited two years earlier in the biggest best
longest AIDS drug trial yet conducted, the Concorde trial in
England, Ireland and France, didn’t dampen the party.) (ii) The CD4
cell count boost was most pronounced among folk who’d been on AIDS
drugs previously, with cell counts of between 50 and 200 mm3.
(iii) In the case of antiretroviral drug-naïve patients
(first-timers) with CD4 cell counts "between 200 and 600 cells/mm3,
nevirapine plus AZT and ddI resulted in a 140-cell absolute change
from baseline at 52 weeks, compared with a 26-cell increase with
ZDV/ddI, and a 2-cell decrease with ZDV/nevirapine." Looking at the
last figure, couldn’t they see the futility of it all? You take AZT
and nevirapine together and your cell count actually goes down by
the end of the trial. We note that the trial overseers reported no
effect on ‘viral load’, that is the measure, according to ‘AIDS
experts’, of HIV infection levels, and their reduction by a given
drug. (Subsequent investigations turned up reductions in ‘viral
load’, but transient only, returning to baseline levels within
weeks.)
On the basis of this crap, Boeringer Ingelheim duly made a pitch
for FDA approval. Obviously nevirapine wouldn’t have made it out of
the starting blocks in any ordinary drug evaluation process. But
this was no ordinary procedure. It was a quickie.
On 21 June 1996 after a fast-track review that lasted just 119
days, nevirapine got its ticket. But it was a qualified one. It was
not to be used on its own. That’s because even on the worthless
measure of efficacy used by ‘AIDS experts’ (CD4 cell counting) it
was ineffective solo. Get that? It doesn’t work as an ‘anti-HIV’
drug on its own. Moreover, there was no evidence to show that the
drug afforded any clinical benefits: made you feel better, and
improved your health. In terms of the Accelerated Approval
Regulations, Boehringer Ingelheim was required to go home, do some
more studies on humans, and come back to describe and verify the
clinical benefit that it proposed the drug might have. Cool new
system. For drug companies. These times being pro-business ones.
A press release on the same day stated, "studies also showed that
the virus rapidly becomes resistant when nevirapine is used alone."
Quite how, no one has ever ventured to propose. Let alone suggest
more frankly that on a plainer interpretation of the data, the drug
is simply ineffective. It’s something like saying: ‘We lost Vietnam
because all those frigging gooks became resistant to napalm and
saturation bombing and the systematic selective assassination of
their intellectuals by our special operatives.’
"Therefore, nevirapine is only recommended for use in combination
with at least one other antiretroviral agent" in the nucleoside
analogue class: AZT, ddC, ddI and d4T. One that the patient hasn’t
taken before. To modulate the laboratory marker – CD4 cell counts –
a bit better than AZT and like drugs on their own. Not make the
patient feel any better. The fact that CD4 cell counts rise for a
while in reaction to exposure to metabolic poisons like AZT even
among HIV-negative people (AIDS 1996; 10:1444-1445) evidently
passed the FDA by. As did the fact that AZT and nevirapine combined
was no good according to the cell-count data.
What’s more, the effects of nevirapine on "surrogate endpoints"
were only noticeable among patients "with HIV infection who have
experienced clinical and/or immunological deterioration." Not for
people appearing well, and whose lab test results were considered
normal, despite having a virus ravaging their immune systems,
according to their doctors.
That nevirapine is extremely poisonous was admitted on the drug’s
label – advising discontinuation "in patients who develop a severe
rash or a rash accompanied by fever, blistering, oral lesions,
conjunctivitis, swelling, muscle or joint aches, or general
malaise." And make no mistake, when the manufacturer talks of rash,
it isn’t referring to a brush with stinging nettles. It means a
generalised symptom of drug intoxication so severe in some cases
that it shows up with thick layers of your skin dying off and
peeling in great chunks. An ad for the drug – featuring the
endorsement of "the dosing convenience of VIRAMUNE" by transatlantic
sailor Mike Schmidt – "WHEN THINGS GOT ROUGH VIRAMUNE DIDN’T GET IN
MY WAY" – explains: "Severe and life-threatening skin reactions have
occurred in patients treated with VIRAMUNE, including
Stevens-Johnson syndrome and toxic epidermal necrolysis. Fatal cases
of toxic epidermal necrolysis have been reported." The ad also
warned of "severe…liver toxicity, including fatal cases", apart from
the bother of "fever, nausea, headache, and abnormal liver function
tests."
It stands to reason that a drug with this kind of appalling
toxicity profile – even worse than AZT – must have some clinical
benefit, shown, if not by the stage it was licensed under the
business-friendly new approval regime, surely by the time it was
offered to the public. But au contraire, as the ad spelt out:
"…indicated for use in combination with other antiretroviral agents
for the treatment of HIV-1 infection. This indication is based on
analyses of changes in surrogate endpoints. At present, there are no
results from controlled clinical trials evaluating the effect of
VIRAMUNE in combination with other antiretroviral agents on the
clinical progression of HIV-1 infection, such as the incidence of
opportunistic infections or survival." Can you credit this? That a
drug so toxic without any proven health benefits should even be on
the market? But this is the land of the free. And after AZT,
anything.
A sucker for every new offering from the drug industry, Project
Inform in the US jumped on it. It promptly released an "ACTION ALERT
[to] URGE CALIFORNIA STATE OFFICE OF AIDS TO APPROVE THE INCLUSION
OF NEVIRAPINE INTO AIDS DRUG ASSISTANCE PROGRAM FORMULARY. …Please
urge the California Department of Health Services to move quickly to
make this promising treatment available! Action Needed: Write or fax
Kim Belshé, Director of the California Department of Health
Services. Urge her to add Nevirapine to the California ADAP
formulary immediately. Stress that including this therapy is
expected to be cost neutral or a cost saving for the state. You can
use the following information from Project Inform’s statement on
Nevirapine to help craft your message [‘etc’]."
Project Inform went on: "Nevirapine may be useful in preventing
mother-to-child transmission of HIV." About which, the sailor’s ad
had some interesting things to say under Pregnancy and
Nursing Mothers. For pregnancy, the drug is "Category C", in
view of the absence of "adequate and well-controlled studies in
pregnant women" so the drug "should be used during pregnancy only if
the potential benefit justifies the potential risk to the fetus." A
risk indicated by rodent studies finding "a significant decrease in
fetal body weight occurred at doses providing systemic exposure
approximately 50% higher…than that seen at the recommended human
clinical dose." As far as nursing mothers go, "a single oral dose"
given about six hours before delivery "readily crosses the placenta
and is found in breast milk" so "mothers should discontinue nursing
if they are receiving VIRAMUNE." So as not to expose the baby to
more than it got in the womb. Because it’s so poisonous. We’ll
return to nevirapine to prevent mother to child transmission in Part
Four. You won’t know whether to laugh or cry.
It is popularly believed by AIDS activists and their friends in
journalism that at recommended doses, nevirapine is safer and less
toxic than AZT. In fact the contrary is the case. Boehringer
Ingelheim’s glossy 86-page Viramune Product Monograph version 3.0
states: "Nevirapine is generally very well tolerated." After letting
us know that people have died of its toxicities. And revealing that
in one major study cited, "The overall incidence of nevirapine
related serious adverse events was 4.3% for patients who received
combination therapy." But in an analysis posted on aidsmyth.com,
Fintan Dunne in Ireland draws our attention to different numbers in
the company’s Nevirapine data sheet posted on the New Zealand
Medicines Safety Authority website: "The major clinical toxicity of
VIRAMUNE is rash…occurring in 16% of patients in combination
regimens in Phase II/III controlled studies. … 35% of patients
treated with VIRAMUNE experienced rash…severe or life-threatening…in
6.6 % of [cases] … Overall 7% of patients discontinued VIRAMUNE due
to rash. Rashes are usually mild to moderate, maculopapular [pimply
blemish] erythematous [red] cutaneous [skin] eruptions with/without
pruritus [itching], on trunk, face and extremities. Severe and
life-threatening skin reactions have occurred in patients treated
with VIRAMUNE, including SJS and TEN (toxic epidermal necrosis).
Fatal cases of SJS, TEN and hypersensitivity reactions have been
reported. … Severe and life-threatening hepatoxicity, including
fatal fulminant hepatitis, has occurred. …" Dunne rightly deplores
the false description of nevirapine toxicity manifest on the skin as
rash, because it is "not cutaneous" nor "local" as the word
suggests, but is "systemically driven…signalling a very serious
illness."
But Boehringer Ingelheim’s claim to the New Zealand government
that ‘rash’ occurs in 35 per cent of cases isn’t true either. It’s
an average figure from all the trials combined. Dunne points out
that in the clinical trial coded B1 1046: "In treatment-naïve
patients, the overall incidence of adverse side-effects is doubled.
Serious gastrointestinal side-effects appear." Concerning the latter
he plausibly contends that these are the result of toxic tissue
manifestations similar to external ones, having quoted a pair of
clinical experts defining SJS/TEN’s "definitive characteristics" as
being "massive epidermal sloughing at the dermo-epidermal junction…
Gastrointestinal involvement may occur because of mucosal sloughing
of the mouth, esophagus, stomach, and rectum [ranging in effect]
from anorexia to development of a necrotic [dead] bowel." And
finally, he points out the finding in B1 1046 that: "Rash affects
50% of subjects – not 35%. Nevirapine and AZT used together produce
side-effects at a rate that diverges strongly [upward] from the
average of all trials."
On 5 January 2001 the US Centers for Disease Control’s
Morbidity and Mortality Weekly Report published a report by
MedWatch, a voluntary drug toxicity reporting system set up the FDA,
entitled Serious Adverse Events Attributed to Nevirapine Regimens
for Postexposure Prophylaxis After HIV Exposures – Worldwide,
1997-2000, reporting severe toxicity after an average of just
two weeks of treatment given to healthy medical workers. The New
York Times summed up on the same day: "Federal health officials
advised doctors yesterday not to prescribe a standard H.I.V.
prevention drug to healthy health care workers stuck by needles. The
drug, nevirapine, can produce liver damage severe enough to require
liver transplants, and has caused death in such use, the Centers for
Disease Control and Prevention said in its weekly report. But
nevirapine should still be used for two other groups, the centers
said. One is in treating people infected with H.I.V., the AIDS
virus. The second is to prevent transmission of H.I.V. from mothers
to their infants during childbirth. … The agency said it and the
federal Food and Drug Administration had identified 22 cases of
severe liver, skin and muscle damage related to nevirapine taken
after possible exposure to H.I.V. from March 1997 through September
2000." Too poisonous for doctors. But great for the rest of us.
Excuding rape victims: "The agency does not recommend nevirapine to
prevent H.I.V. infection among people recently exposed to the virus
through unsafe sex, [the CDC’s Dr Julie] Gerberding said." But
including pregnant women. That’s because the "benefit outweighs the
risk, largely because the mother and child take only one pill," said
the CDC’s Dr Helen Gayle. "No serious adverse effects" had been
noted in pregnancy studies. Gayle was wrong about that, as we’ll
discover in Part Four. The UN AIDS programme accordingly supported
the CDC’s recommendation that the drug be given to pregnant women
and was "working with Boehringer Ingelheim to start programs in
developing countries." Just in case you never knew that when it
comes to pharmaceutical drugs, we’re all one big happy family.
After securing the US market by getting it past the FDA, the rest
was a breeze. As it had been with AZT. Boehringer Ingelheim turned
next to the European Agency for the Evaluation of Medicinal
Products, claiming in its submission: "The pharmacology safety
programme addressed among others, effects on central and autonomous
nervous system, cardiovascular, and renal respiratory systems and
did not reveal any severe side effects at relevant dose levels
and/or concentrations." These "toxicokinetic data" were derived from
studies on "both rats and dogs", on the basis of which the company
proposed that "there seemed to be acceptable safety margins" –
notwithstanding that clinical trials with humans as test subjects
had already revealed a shocking toxicity profile. The Safety
discussion reads like an excerpt from Orwell’s 1984. Suffice
it to say for present purposes that it was obvious even then that
nevirapine was exceedingly poisonous. As revealed by its effect on
the liver, and ‘rashes’ of such severity that some patients died.
Both of which toxic manifestations had been predictable from the
reactions of test animals, discussed earlier in the dossier. But
don’t hassle. Boehringer Ingelheim smoothed things over with this
public-spirited precaution: "Therefore having reassessed the
risk/benefit profile of nevirapine, the warnings concerning the
occurrence of these events have been reinforced. In addition, new
recommendations for the liver and cutaneous monitoring of
patients…have been introduced through an urgent procedure."
The EMEA approved the drug on 5 February 1998. On the advice of
an expert panel however, the EMEA recommended that nevirapine be
categorised in its register of approved drugs for prescription
"under exceptional circumstances" only. Being a very dangerous drug.
And the EMEA required commitments from Boehringer Ingelheim to
conduct further clinical studies, on the basis of which it would
make a final risk/benefit evaluation.
The trouble is that new bits of fine print on the paper in the
box didn’t make any difference. Inasmuch as strychnine is
strychnine. Reports continued to flow in of people suffering serious
skin and liver damage, some fatally. On 12 April 2000 the EMEA got
nervous, and issued from London an urgent EMEA PUBLIC STATEMENT
ON VIRAMUNE (nevirapine): SEVERE AND LIFE-THREATENING CUTANEOUS AND
HEPATIC REACTIONS, which it "thought…necessary to provide…to the
public." The "prescribing and patient information" contained in the
package insert was to be substantially revised and amplified
further, essentially boiling down to: ‘If you get very sick very
quick as other people taking this stuff have done, with your liver
packing in, and your skin starting to rot, especially mucosal
surfaces like eyes, mouths and the lower orifices, then chat to your
quack. Even think about ditching it.’
In November 2000, the FDA in the US caught up with the Europeans.
It issued an alert of its own concerning nevirapine liver toxicity,
after a study found that it caused a third of patients to quit
taking the drug – as against the picture painted in Boehringer
Ingelheim’s glossy Viramune Product Monograph 3.0 dished out
at the 13th International AIDS Conference in Durban a
couple of months earlier: "Nevirapine related hepatitis was reported
infrequently in clinical trials. The incidence…was 1.0%…in BI
clinical trials (Pollard et al. 1998) … In the four
controlled trials of combination therapy…treatment related hepatitis
was observed in…1.1%… The occurrence of hepatitis and other liver
related events with double and triple therapy regimens including
nevirapine from 13 recently completed and currently ongoing clinical
trials has also been reported (Pollard et al. 1998). In these
13 studies, the overall incidence of hepatitis possibly related to
nevirapine (0.5%) was similar to those in the earlier studies
discussed above. … Fatal cases of hepatitis have been reported."
Is this the same drug we’re talking about?
Part Two
I therefore claim to show, not how men think in
myths,
but how myths operate in men’s minds without their being aware of
the fact.
-- Claude Lévi-Strauss
Boehringer Ingelheim had a bit more trouble pushing past the
medicines regulators in Canada than it did in the US and Europe. Its
licensing application filed on 13 June 1996 had bombed. A second one
was wallowing. The Therapeutic Products Programme of Health Canada,
a division of the Health Protection Branch, couldn’t see any
benefit. Only terrible toxicity. But the company wasn’t used to
taking no for an answer. Who do you red coat naffs think you are?
Telling us to bugger off. So its surrogates got the politicians to
interfere. Knowing how to get things done. On 5 March 1998, a mob of
Treatment Action Campaign types – the Treatment Information Project,
an arm of British Colombia People with AIDS – gatecrashed a meeting
attended by Health Minister Allan Rock at St Paul’s Hospital in
Vancouver and began mouthing off that his drug regulators didn’t
know what they were doing: they "do not understand how the drugs
work", unlike the US FDA which has a "superior understanding." Not
only stupid but too independent too – characterised, in the BCPWA’s
report of the day’s fun, as "ineffective in coordinating its work
both internally and internationally. Drug company representatives
express enormous frustration that there is little consistency in the
personnel [that Health Protection Branch] assigns to work on a given
file. As well, there seems to be little opportunity for fluid,
ongoing dialogue during the review process. Add to this the fact
that components of a review that could be done concurrently such as
clinical and chemistry/manufacturing are instead done sequentially.
There are also opportunities for international co-operation that
Canada takes little advantage of."
Hell of impressed by the activists’ pitch, Rock was full of it
when stirring things up down at the TPP. A week later, taking a
sudden interest in the drug approval process, he asked the guys how
it worked, specifically wanting to know what the hold-up with
nevirapine was, since it was already approved in America, Europe and
elsewhere. Five days later he got his answer: It mentioned that
nevirapine was in the final stages of the review process (in a
renewed application). It explained that, "Differences in the
regulatory status of antiretroviral drugs in Canada as opposed to
the United States, relate to several factors, namely: differences in
submission filing dates [the trick being to file in the US first and
later in the secondary markets to pressurise the latter’s regulatory
authorities into conforming with the US, where just about any shit
goes down – 80 per cent of all licence applications approved
nowadays], restrictive regulatory provisions [slightly higher
standards in Canada – drug regulators being edgy there in the wake
of the thalidomide disaster, particularly bad in that country thanks
to regulatory inertia and laxity at the time], and limited
resources. …Differences in submission filing dates stem from the
tendency of pharmaceutical manufacturers to file their new drug
submissions in the United States (US) first, primarily to get access
to and secure a wider market share." Working the system in other
words. The memorandum pointed out that in Canada there was none of
this ‘conditional approval’ business, with manufacturers coming up
with evidence of clinical efficacy only after the release of a drug.
But they were looking at developing such a scheme. To keep up with
the Americans and Europeans. It then went on about how hard we’re
trying, but we’re low on dough. Concluding with the canniness of a
cat pitching for cream: "There has been a continual erosion of the
appropriated funds…required for sustaining and enhancing regulatory
review activities related to drugs. … Without infusion of additional
resources, the TPP will not be able to respond to the continuing
demand for shorter review times for HIV/AIDS drugs." Nothing if not
upfront about their pork-barrel demands, these blokes. The
bureaucrats playing the politician like a banjo. Scratch our backs
and we’ll scratch yours.
On 9 April 1998 Rock replied: Get the new conditional approval
regime in place. Without delay. We’ll worry later about drawing up
some regulations to deal with drug companies not complying with
their obligations to come back with the evidence that their drugs
out in the market actually worked. That’s what he said – sure did.
Now we recall that according to ‘AIDS experts’, nevirapine’s
benefits, if any, are very modest indeed. Modulating CD4 cell counts
slightly better in combo with older drugs than the older drugs
alone, but only in the case of people with low CD4 cell counts.
Certainly no clinical benefits shown in terms of improved health.
But that’s not what the lobbyists told him. A swallower evidently,
the politician enthused: "As the Department is no doubt aware…the
new antiretroviral drugs are able to cut death and disease rates
dramatically… With respect to the drug Viramune (nevirapine), I am
told that this drug is available in 75 countries but not in Canada.
I am also told that the drug has been rejected once by HPB and is
now under second review. Please advise whether this is true, and if
so, the circumstances."
On 22 April 1998 Rock got his next answer, confirming that a
conditional approval regime was being implemented. Also that
nevirapine had been approved elsewhere but not at home. The
interesting bit was why: "…the review of the new drug submission for
Viramune did not reveal any conclusive effects on clinical end
points nor on surrogate marker end points to support the benefit of
Viramune in treating patients with HIV disease [i.e.
even the latter were too flimsy]. The efficacy of Viramune was not
clinically significant when evaluated against internationally
recognised standards of efficacy for drugs used in the treatment of
HIV. There are, in addition, safety concerns associated with
Viramune use in clinical trials. On March 6, 1997, a Notice of
Non-Compliance (NON) was issued by the Therapeutic Products
Programme. On July 2, 1997, the manufacturer filed a response to the
NON. In the absence of scientific evidence of efficacy and concerns
relating to safety, the data available for Viramune are judged to be
inadequate to support the clinical benefit of the drug."
On 23 April 1998 Rock’s office addressed further questions to the
regulators. Their answer the following day reiterated adamantly,
"The review of the drug submission for Viramune by the Therapeutic
Products Programme found that there was an absence of scientific
evidence of efficacy and that there were also concerns about safety.
The data available for Viramune were judged to be inadequate to
support the clinical benefit of the drug and a Notice of
Noncompliance (NON) was issued on March 6, 1997. This review
decision will be forwarded to the Expert Advisory Committee on HIV
Therapies for further review."
Doing as bidden, the Therapeutic Products Programme rushed a new
conditional approval system into place. The next development was –
you guessed it – nevirapine was back on the table for "a priority
review ... a quick response would be much appreciated" (per
Joyce Pons, Submission Screening Officer in the Bureau of
Pharmaceutical Assessment, in an internal memorandum dated 8
September 1998). Following which it was conditionally approved. With
pleasing alacrity, on the 17th, just over a week later.
But only for use in combination with other old antiretrovirals, not
on its own. No good for that. We speak of a drug found to be useless
after two unharried assessments – the manufacturer having been
unable to come up with any evidence of clinical benefit. Or any
significant effect on laboratory test markers. Despite ample time
and opportunity to come up with the goods. In not one but two
licence applications. But approved for consumption by the public
under the new rules. The process being a quick one. Because look,
this is an emergency. The activists say so. So there’s no need to
show a drug works anymore. As long as you promise to come back and
show us later.
A condition was duly attached to the licence, being, that’s
right, that Boehringer Ingelheim come back with some evidence of
clinical efficacy. Fine, it promised. Just one snag. In the headlong
rush to oblige the Germans, the Canadians hadn’t got around to
writing the rules concerning the enforcement of such undertakings.
Internal communications reveal the confusion: Chris Turner, Manager
of the Continuing Assessment Division asked, "Who is responsible for
following up the conditions? … We do not have the review staff at
present to accept such an assignment…" Ann Sztuke-Fournier of the
Advertising and Promotions Unit replied, "As discussed this is still
not clear. The conditions are unknown to me and the regulatory
impact as well." Eric Ormsby, Acting Director of the Office of
Science-Risk Management Methods in the agency noted, "We still do
not know whether we have the authority to remove an NOC [Notice of
Compliance] if they do not provide the information agreed upon.
Sheila Hills in BPA is writing a guideline or something regarding
information required. I don’t know much more." Chris asked, "Is the
NOC with conditions actually finalised yet? I thought there was to
be a guideline. What is the regulatory authority for such
‘limitations’ at present?" Ann wrote to Eric: "As mentioned by
Chris…do we have a regulatory authority for these limitations? I am
not aware of any formal commitment or agreement to conduct
post-marketing surveillance for this drug or under what conditions
this drug has been approved."
Vicky Hogan, Head of the Monitoring and Evaluation Unit, set out
her agency’s "concerns." Nothing was being done to "educate the
medical community" about the new conditional licensing policy, she
said. In Boeringer Ingelheim’s release about the drug to physicians,
"information about the conditions was not highlighted and the
prescribing physicians [who] received that information were NOT
informed about the outstanding concerns about efficacy associated
with this drug. …physicians are under the impression that this
drug…is considered…to be both safe and effective." There was "deep
concern," she said, "that we do not have [an] active surveillance
program in place yet…" She wondered what "compliance action" will be
taken if manufacturers do not comply with the conditions imposed on
their provisional licences, and concluded by suggesting that "the
programme needs to act fast to communicate this new policy to the
medical community and to develop some operational infrastructure
around it. I am particularly concerned that the vast majority of the
medical community does not know the significance of a [provisional
licence] and so is left to make prescribing decisions without the
benefit of this knowledge and that there seems to be a good deal of
confusion in terms of who, in TPP, does the follow through on
monitoring conditions set forth in [a provisional licence]." Never
mind the Mounties. More like the Keystone Cops.
Once Boehringer Ingelheim had succeeded in stiffing the Canadian
government too, its whores began to sing on cue: Julio Montaner,
driving a nice new Beamer, no doubt, on his nevirapine trial
supervison fees, enthused: "We are extremely pleased to see this
valuable new treatment alternative in Canada…" International AIDS
Society President Mark Weinberg (at the time), his back pocket
similarly stuffed from overseeing nevirapine clinical trials,
applauded: "Nevirapine is a wonderful antiviral drug and its
approval now means that Canadian patients, and their physicians,
will have increased options for the treatment of HIV disease. I
fully expect that people will live longer and enjoy an increased
quality of life as a result of this long-overdue decision by Health
Canada to approve nevirapine." I watched this guy with his Colgate
smile glad-handing several dazzled women at a lunch table at
Durban’s AIDS Conference in 2000 a couple of paces from where I sat.
The International AIDS hero. And I couldn’t help recalling that
timeless summation of Eichman: "The banality of evil." (Four months
earlier he’d proposed that troublemakers like me be arrested and
imprisoned.) Our very own nevirapine fan, Supreme Court of Appeal
Judge Edwin Cameron enthused about the drug in similar vein during
an interview on the M-Net television programme Carte Blanche
on 4 November 2001. Nevirapine, he said, "is a very good drug. It’s
been offered free to our government to give to mothers who are about
to have babies and our government has not yet taken up that offer,
which is a tragedy I think." The tragedy of it we’ll examine in Part
Four. The tragedy of Edwin Cameron you can read in Just say yes,
Mr President: Mbeki and AIDS.
Hot on the heels of its licence grant in Canada, Boehringer
Ingelheim spokesman Fred Harris announced a quick marriage of
convenience. To a sugar daddy. And golly, guess who: "Boehringer
Ingelheim (Canada) Ltd, recognising Glaxo Wellcome Inc. as a leader
in the development and marketing of products for the treatment of
HIV/AIDS, has decided to enter into a marketing agreement to
provided a quicker and more focussed introduction of the product
into the Canadian community." So we can get it out there. Like
people are dying.
Part Three
A few men think, but all will have opinions.
-- George Berkley
When you consider how easily Boehringer Ingelheim rammed
nevirapine past the First World Canadians, just think how soft the
defences of developing countries are to the predations of such
giants with all their financial and propaganda resources. Countries
like ours. So predictably there was none of the initial Canadian
trouble here, with annoying government pharmacologists saying, ‘Your
drug is pure shit. We don’t want it here. Take it away. Go and push
it somewhere else.’
On 22 April 2000 the Independent Online quoted Boehringer
Ingelheim’s local corner merch Kevin McKenna telling us that
nevirapine had just been approved: "It was very efficient. It was
very quick," he said. We never doubted it would be. Not a question
raised. The South African Medicines Control Council being packed
with useless dregs. As we saw with how they blew the AZT enquiry
ordered by President Mbeki. Being both blind and thick. Disregarding
the key literature. All the latest stuff on foetal toxicity
especially. Not to mention Papadopulos-Eleopulos’s et al
exhaustive review of the molecular pharmacology of AZT, published on
1 September 1999 in Current Medical Research and Opinion a
month before Mbeki’s safety enquiry directive (see endnote), which
concluded that not only is AZT very poisonous, but that it cannot,
and in fact, by all conventional measures, does not have the
pharmacological activity claimed for it by GlaxoSmithKline. However,
the paper dealt with tricky stuff like whether AZT is
triphosphorylated intracellularly to its inhibition concentration
in vivo, and frankly, to expect the MCC’s members to exercise
their minds around such abstruse technicalities would be asking too
much. Because let’s face it: We’re just a bunch of rubber stamps for
the drug industry. And if the FDA hasn’t bothered, why should we?
Just because the President asked us to. Tipped off by some prick
lawyer.
Soon after licensing in South Africa, nevirapine hit a bump in
the road. Approval of the drug by the MCC presented a grand
opportunity to Triangle Pharmaceuticals, an American pharmaceutical
corporation founded by former GlaxoSmithKline Director of Research
and AZT promotor, David Barry. Eager to cut a slice of the
AIDS-drugs action, it needed some guinea pigs on which to try out
its experimental drug Coviracil (Emtricibatine, alias FTC),
ahead of a licence application to the FDA. Penurious South African
blacks being ideal. Being unimportant and dispensable. Not such a
fuss if they get hurt or killed. Nice and cheap too. Compared to
what such test subjects cost back home in the US. Fifty rand to each
for every hospital visit – about five dollars. Triangle engaged
Quintiles Transnational, described at the time by a Yank newspaper,
the Raleigh News and Observer, as "the world’s largest
pharmaceutical services company", to conduct a clinical trial with
Coviracil in combination with nevirapine and two other drugs,
lamivudine (3TC, an AZT lookalike) and stavudine (d4T, another one).
Dr Mariette Botes, an ‘AIDS expert’ at the University of Pretoria
and head of the AIDS clinic at Kalafong Hospital in Pretoria, was
hired to run the trial there, one of sixteen sites at which the
study was conducted. Its subjects were drawn from Atteridgeville, a
largely impoverished dormitory complex outside Pretoria for Sotho
speakers. The study was called FTC 302. It was an abattoir.
Social workers at Kalafong Hospital, who noticed that many people
on the drug trial were suffering severe ill effects, tipped off Pan
African Congress MP Patricia de Lille. The right politician to get
involved, having more go than just about all of them put together.
On 6 April 2000 De Lille was reported telling the Natal Witness
that she had uncovered "a nest of abuse and exploitation. … One
patient developed a rash all over his body and still has marks on
the face. He told Dr Botes that this had happened since using the
drugs, but the doctor said it was not the drugs causing the rash,
but the HI virus." Severe skin damage being a brand-new AIDS
indicator disease, according to Dr Botes. She’d never heard of Toxic
Epidermal Necrolysis apparently. For which nevirapine is famous.
Our Minister of Health Dr Manto Tshabalala-Msimang also heard the
news, was damned unhappy about it, and told the Medicines Control
Council so. The president of the MCC at the time, Helen Rees,
responded nonchalantly that "many AIDS medications could cause liver
and other problems. But the combination therapy can make a huge
difference to people’s lives." The kind of thinking we expect from a
doctor. For whom drug company propaganda passes as medical knowledge
– she even speaks as the advertisements do. At Tshababala-Msimang’s
insistence, the MCC nonetheless called off the trial. Or tried to
because Quintiles Transnational just pushed right on with it. Since
we just do what we like in developing countries. The media reported
"an uproar in medical circles" over the termination of the trials.
But of course. To be expected, as I said.
Several people died on the drugs. Five women at Kalafong hospital
according to Tshabalala-Msimang, the Medicines Control Council and
Professor Geoffrey Falkson of the University of Pretoria’s Ethics
Committee. Only two, Kalafong Hospital sources were later quoted in
the press. Actually only one, a man, claimed hospital superintendant
Hanli Dafel. In fact none, said Triangle’s Dr Ian Sanne to
investigative journalist Vivienne Vermaak – none at Kalafong
Hospital, but seven people at other centres.
An official investigation found that two of the dead died of
liver failure, one of pancreas failure (both conditions caused by
acid lacidosis, a standard side effect of antiretrovirals), and two
of neurological damage (likewise). Other trial subjects suffered
deafness, impaired speech, anal bleeding, sores that wouldn’t heal,
abdominal pains, weight loss, fevers, pneumonia, insomnia, vomiting,
and depression. The investigation concluded that nevirapine had
probably caused the liver damage that had killed two of the women.
Not surprisingly, since of all so-called antiretroviral drugs on the
market, nevirapine is top of the pops when it comes to wrecking
livers. Even worse than nucleoside analogue drugs in the AZT class,
and they’re not shy. Boehringer Ingelheim’s McKenna ducked and dived
at the flashing blue light: "My information is that the actual link
to nevirapine is inconclusive…" His bosses in Germany backed him up
with a formal press release on 10 April 2000: "…in a clinical trial
in which patients are taking multiple drugs, it is not possible to
determine with certainty, which drug, if any, may have caused
the…deaths. [That’s the joy of mixing dangerous toxins made by
different companies: A backdoor out when things go wrong.] …
According to news reports, there was a higher than expected
incidence of liver toxicity in the study. In fact, the incidence of
liver toxicity seen in the study is in line with what is commonly
seen in similar studies of triple combination antiretroviral
therapies in HIV-infected individuals. [A local doctor commenting
anonymously in the Mail and Guardian remarked similarly; he
didn’t see why there should be any bother about this. We expect a
few to peg off on these AIDS-drug trials, he said; it’s normal.] As
with all potent antiretroviral treatments, there are known side
effects of nevirapine as described in the labelling product." In
all, an exercise in wordplay more fascinating even than Bill
Clinton’s about his side-ass jinks in the Oval Office.
Apropos the liver damage observed, since the liver toxicity of
nevirapine is the most acute (rapid) relative to the other drugs on
trial, it was a fair bet to blame it – on a preponderance of
probabilities, as we lawyers say. "Which drug, if any" suggests
doubt that the deaths were the result of drug intoxication. But the
causes were diagnosed. And they weren’t AIDS indicator infections or
malignancies. AIDS journalists Lynne Altenroxel and Anso Thom
reported in the Independent Online on 6 April 2000 that,
"Experts have questioned whether nevirapine could have caused the
deaths, as the drug had already undergone clinical trials of its own
before being registered for use in 1998." To these airheads,
registration meant it was safe apparently. Nevirapine being the new
drug that gee-whizz journalists of their calibre have switched to
advocating, since AZT for babies seems to have got rather messy. All
those nasty foetal damage reports in the medical journals. And when
‘AIDS experts’ talk, don’t we just swoon? But we recall Vicky Hogan,
Head of the Monitoring and Evaluation Unit for the Canadian
Therapeutic Products Programme, stating her agency’s concerns about
the fact that in Boeringer Ingelheim’s jubilant communique to
doctors after a conditional licence had been granted, "information
about the conditions was not highlighted and the prescribing
physicians [who] received that information were NOT informed about
the outstanding concerns about efficacy associated with this drug.
…physicians are under the impression that this drug…is considered…to
be both safe and effective." Boehringer Ingelheim seemed to be
conceding that, look, a cocktail of arsenic, cyanide and strychnine
is more poisonous than single shots. But we know this. We say so on
the label. So what are you complaining about? As for "potent
antiretroviral treatments", Debating AZT will have brought
home that their only potency lies in their toxicity. You can’t make
a vicious runt with a knife ‘the heavyweight champion of the world’
just by calling him Muhummad Ali. Especially nevirapine, brave only
in gangs. But still useless.
The FDA grumbled about the look of things, sending Triangle
Pharmaceutical shares into sharp descent in the US, with more than a
third of their value shaved. The company’s executive vice president
Carolyn Underwood hastened to exculpate her Coviracil, blathering,
"The unfortunate part is, it is really hard to sort out how much of
this is a political issue. It is escalating and we are caught in the
middle of it." Like Somalia? You would have thought that the deaths
were more than a political issue. And that the poisoned were "in the
middle of it." About whom she expressed not a peep of condolence.
Instead, after the plug was pulled on the trial, she said, "There
are no other drugs in South Africa for them to receive. We are most
concerned about the possibility that these patients will be left
without therapy." Right after the news that it was killing and
injuring them. Notwithstanding the horrible toxicities that she
observed among these adult clinical trial subjects, our favourite
MP, Patricia De Lille, nonetheless deplored government’s reticence
in exposing babies to the drugs that caused them: "It is unfortunate
that [Tshabalala-Msimang] has used the tragic event of deaths during
the trials to make a political point that justifies her doing
nothing to stop mother-to-child transmission," she said.
Apart from suffering terrible fatigue, abdominal cramps and
headache on Dr Botes’s medicines, one woman, Gladys Mamosodi, went
blind for two weeks. The doctor told her it was her AIDS coming on.
But strangely, she partially recovered her sight after quitting the
drugs. Which makes sense since nevirapine is particularly good,
Boehringer Ingelheim warns, at rupturing mucosal tissues like those
found on the surface of your eyes. The other symptoms won’t be
anything new to you, having read Debating AZT, and knowing
what you do now about ‘antiretrovirals’. Afraid about what was
happening to her, Mamosodi approached Botes, asking for her medical
case file. It’s gone missing, she was told. Unconvinced by this
excuse, she returned to demand its production again, this time
taking her mother along for reinforcement. You can’t have it, Botes
responded; why, you tore it up yourself. Hearing this extraordinary
news broke Mamosodi’s heart. She passed on from this world to the
next soon after. But not before Vermaak had got her story,
masquerading as a nun in a borrowed habit to get through the
hospital door. As if to administer the last rites, but really to ask
questions and peer into closely guarded medical files, when the
white madam wasn’t looking. Mamosodi shared her tale kneeling on the
floor, emaciated, incontinent in nappies, her head in Vermaak’s lap.
Groaning in agony, on her way out. Her subsequent demise chalked up
to TB on her death certificate. Since she’d been put in a TB ward.
Everyone knows that these HIV-positive blacks get TB. Except that
she never had TB. Said four TB tests. When Vermaak put it to Botes
that people on the trial like any other patients had a basic right
to their own medical information, Botes answered brightly, "I’m not
aware of that. I’m not a legal expert."
Vermaak took the story to the MNet television programme Carte
Blanche, a platform for spilling beans every Sunday night, prime
time. The accused rang their lawyers. There was a set-to. How dare
MNet tell such lies. Do you want us to sue you? MNet reacted by
repudiating Vermaak’s investigation by way of a televised
disclaimer, denouncing the exposé and apologising for all the hard
feelings it caused. Vermaak, MNet suggested, was both incompetent
and dishonest: Mamosodi had never been on the antiretroviral drug
trial. Said Dr Botes. This was the principal falsehood for which
Vermaak was publicly flayed. Yet Mamosodi insisted to Vermaak that
she’d been on antiretroviral drugs, nevirapine included. And that it
was when she was given the AIDS drugs that she started feeling
really sick. No, no, Botes told Vermaak. Mamosodi had actually been
on an antifungal drug trial. She’d been given an "innocent" drug
that "couldn’t cause the side effects [that she’d] complained of."
Except that her signed Informed Consent form, finally produced,
warned of some pretty dark ones for the "innocent" drug too, like
hearing loss and kidney damage.
But it turns out that Vermaak was right about those
antiretrovirals after all. Although Mamosodi booked in to volunteer
her body to medicine, for the pittance it would earn her family,
with no more than a sore throat, Botes, being a terribly kind
person, admitted at the enquiry subsequently conducted by her
university that she’d put her on antiretrovirals. Being a
humanitarian, apparently. Didn’t write a prescription though. Didn’t
see the need. Not even the legal one. And of course there was
nothing in her file about such drugs. All very odd. But nothing
odder than Botes’s reluctance for that medical file to see the
light. First withheld on the basis of a lie, and then another, and
then finally produced with important contents missing – nothing
about Mamosodi being given an experimental combination of
antiretroviral drugs, and of course nothing about her blindness that
developed after she commenced taking them. Or the uncontrollable
diarrhoea and myopathy that set in and continued even after she
stopped. Until she died.
Vermaak also investigated the "rash" case that De Lille had
encountered – a classic case of Stevens Johnson Syndrome or Toxic
Epidermal Necrolysis. A well documented ill effect of swallowing
nevirapine. Big words for poisoning off skin cells in thick swathes.
We’ll call the unlucky subject "Tsietsi Madimabi" since he’d prefer
his real name not be told. He told Vermaak: "A rash broke out all
over my body. I wanted to throw up all the time and had a fever."
Within days, Madimabi’s "rash" had developed into suppurating open
sores, head to toe. He couldn’t walk. As the toxic reaction began to
intensify, he desperately tried reaching Dr Botes, but her cellphone
number just rang and rang. He’d forgotten that his copy of the
Informed Consent form contained an emergency hotline number. But it
wouldn’t have helped to phone it either. It was wired to a telefax
machine in a small office at the hospital. So Vermaak found out when
she tried it. Hardly a fitting medium for a discussion of your
life-threatening toxic drug reaction. And not much use if you live
in a shack and don’t own a fax machine. Who in Atteridgeville does?
But it wouldn’t have been any use having such a hi-tech gizmo
anyway. Because the fax machine was unmanned most of the time. On a
lucky day it would be staffed by volunteers. Off the street, knowing
nothing about the management of drug toxicity emergencies. But you
have to understand; we had to contain our costs. This is how
capitalism works. And anyway they were only blacks.
Fearing that it was the treatment that had made him sick,
Madimabi staggered into casualty at Kalafong hospital where he
showed his pills to the quacks. They had the rare good sense to
instruct him to quit the drugs immediately and to book him in,
noting on his medical file: "Grade 4 skin rash due to nevirapine" –
Stevens-Johnson syndrome in other words. Botes paid Madimabi a visit
a few days later. Except her diagnosis was different: HIV was to
blame, she said, not the tablets. Being an ‘AIDS expert’. But then,
on 16 November 2000, she dumped him from the trial. A funny thing to
do, considering: Aren’t the drugs supposed to rescue you from the
march of AIDS?
Helped by social workers and de Lille, Madimabi and other trial
subjects also seriously injured by the drugs filed handwritten
complaints with Pretoria University’s Ethics Committee. We live in a
constitutional democracy now. We’re not apartheid untermenschen
any more. We have rights. We’ve been burned. We expect something
should be done.
They were expecting too much. The gist of their complaints was
that they didn’t understand the Informed Consent forms and that the
drugs caused them to suffer unexpected serious adverse effects. But
they got ripped up. You signed; haven’t you heard of the caveat
subscriptor rule? The hospital filed an all-clear report with
the MCC. It didn’t go down well. Particularly since only four of the
eight complaints filed had been investigated. Do it properly, the
MCC ordered. Eventually, after a year of boiling dissatisfaction and
grassroots politicking in the township, a formal hearing was held
into the deaths and injuries that occurred on the trial.
Madimabi complained at the enquiry that he never understood that
taking the pills might have caused him to suffer such terrible
injury. His grasp of English as a second language wasn’t great, but
it wouldn’t have helped to have spoken the Queen’s best in any
event. The Informed Consent form for the clinical trial, read out to
him before he signed it, went: "Side effects that have been seen
with nevirapine (Viramune) are rash, fever, nausea, headache, and
abnormal liver function tests. These symptoms will be closely
monitored." They weren’t, as we know. But the mild ill effects so
described are a far cry, you’ll agree, from the fate that befell
Madimabi – consistent with the toxicity alert appearing on the
nevirapine package insert for First World consumers, reflecting what
had "been seen" more frankly: "Warning: Severe and life-threatening
skin reaction (Stevens-Johnson syndrome, toxic epidermal
necrolysis), including fatal cases, have occurred in patients
treated with Viramune."
There was something else about that Informed Consent form that
bothered Madimabi. All recruits to the drug trial were in good
health with CD4 cell counts within what ‘AIDS experts’ consider
normal range, and all had low or undetectable ‘viral loads’. But the
‘AIDS experts’ had told Madimabi that he was infected by a deadly
germ, and had ‘HIV-disease’. And that it would be just a matter of
time before his health crashed, thanks to some or other
‘opportunistic infection’. Which surprised him since he felt as fit
as a fiddle. As such news does to most people who light up these
tests in good health. Told he was actually diseased – according to
the tests – he was invited to take the trial medicines. He
understood that the drugs would keep him well – quite reasonably,
having regard to what the Informed Consent form stated: "It is
expected that the suggested study treatment will lead to reduced
severity and frequency of opportunistic infections (the common
diseases that go along with HIV- infection)..." Who wouldn’t jump at
the chance offered by the kind doctors? Gee, they even pay us to
take the medicines. Unfortunately for Madimadi that they didn’t
share with him the contrary information appearing in the package
insert for the drug that nearly killed him: "Information for
patients: Patients should be informed that Viramune is not a cure
for HIV infection and that they may continue to experience illnesses
associated with advanced HIV-1 infection, including opportunistic
infections. Treatment with Viramune has not been shown to reduce
the incidence or frequency of such illnesses...." Because had
Madimadi known that, he wouldn’t have been so keen to join the
experiment. On him.
The enquiry delivered a Biko verdict: Everything was found
hunky-dory. Just like the old days. The mostly white AIDS activists,
journalists and human rights campaigners in South Africa who clamour
for AIDS drugs for blacks at every chance were strangely mute for a
change. We didn’t see a single one of them with their tee shirts and
placards and banners at the funerals. But most noteworthy was MRC
President William Makgoba’s silence in the affair. The guy who’d
presented a paper at the 13th International AIDS
Conference in Durban in July 2000, called Ethics of AIDS Research
in a Developing Country – Balancing Power in Disguise. Making
points like: "…temptations may remain to subordinate the welfare of
the volunteers…and treat human beings as a means to an end. Research
may also be motivated by financial gains where expediency obscures
ethics to the detriment of volunteers and the integrity of science.
… Informed Consent has become one of the major ethical
transgressions of our time – particularly in developing countries.
Informed Consent has four essential components: disclosure of all
relevant information about the research; comprehension by the
prospective participant of this information to make an informed
decision… However codes and requirements alone do not guarantee
protection… In South Africa…most of our subjects speak…a different
language from the languages of the researchers and practitioners;
secondly most subjects in our countries are poorly informed with
substandard education. … The weak and the powerless in our society
require a different form of approach…in order to fully understand
the magnitude and implications of signing an informed consent form.
…the tendency is for power to prevail over protection."
Finely spoken, William. We all agree. So what did you have to say
to your Masters in the drug industry when these people were dying
poisoned, others badly injured? Apart from Yes Sir; No Sir; Three
bags full, Sir. Except of course in this country you say Baas.
Part Four
There is no expedient to which man will not
resort to avoid the hard work of thinking.
-- Thomas Edison
In January 2001 nevirapine was approved by the South African
Medicines Control Council for use as a single drug to prevent mother
to child transmission of HIV. On the strength of a study so inept
you can’t believe your eyes – the one that founded the Treatment
Action Campaign’s successful application to the High Court for an
order compelling our government to forget about the cautious
exploratory trials that the Medical Research Council was conducting
at pilot sites around the country, and to supply nevirapine to every
HIV-positive pregnant woman showing up at government hospitals
without further ado.
Laura Guay, an ambitious staff-doctor in the Pathology Department
of Johns Hopkins University School of Medicine, in the city of
Baltimore, Maryland, US, got the bright idea that nevirapine would
be her ticket to stardom if she could show that it saved babies from
their mothers. In 1997 she flew in to Kampala, Uganda with a team of
researchers to conduct an experiment on pregnant black women there.
Her idea was to compare the effectiveness of nevirapine versus AZT
versus placebo for preventing mother to child transmission of HIV.
All treatments commencing at labour.
The study was reported in Lancet on 4 September 1999 in
all the usual posh language: Intrapartum and neonatal single-dose
nevirapine compared with zidovudine for prevention of
mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012
randomised trial. South African ‘AIDS experts’, activists,
pharmaceutical regulators, health officials, opposition politicians,
journalists, human rights lawyers and judges were all tremendously
wowed. Here was rock-solid proof of nevirapine’s efficacy for saving
babies’ lives. Summed up in the assertions of our Medicines Control
Council’s Dr Jonathan Levin in a disgracefully inadequate answering
affidavit that he made in the TAC's nevirapine case: "NVP would save
10 out of every 100 babies born to HIV-positive mothers" and "HIVNET
012 provides conclusive evidence of the efficacy of NVP." With
friends like these on your side, who needs enemies? Is it any wonder
our government lost the case?
Guay’s nevirapine study was an unbelievable mess. To read her
referring to the drug’s "potent antiviral activity" and "safety
profile", i.e. very effective against HIV and perfectly safe
in pregnancy, contrary to what was already known, was just a
foretaste of what was to follow.
It’s elementary that a drug trial should be randomised,
placebo-controlled, and double-blind – meaning its subjects should
be treated or not treated on the basis of a random assignment; test
drugs and dummies should be equally distributed; and neither the
hospital doctors nor the patients should know who’s on what. There
should also be an untreated control group in the trial, given
neither the test drugs nor placebos, in order to exclude the
possibility of outcomes hoped for by the researchers showing up
without any intervention at all – since the administration of
placebos can have the strangest effects, as we’re about to see. And
of course there should be a big enough number of test subjects on
the trial from which to draw meaningful conclusions.
Guay apparently knew most of these basics when she teed off,
because the trial she conceived "was originally designed to be a
randomised, placebo-controlled, double-blind phase three trial of
1500 mother-baby pairs to investigate the safety and efficacy of
oral zidovudine and oral nevirapine for the prevention of vertical
mother to child transmission of HIV-1 from pregnant women to
neonates in Uganda." A fair start, except that Guay didn’t think to
study an untreated control group. A not insignificant omission,
seeing that the American CDC, studying the effect of AZT for the
same purpose, reported that placebos apparently reduced the
transmission rate (18.6%) when compared with untreated controls
(24.2%) – leading the researchers to observe: "The lower than
expected background transmission rate highlights the importance of
having included a randomised, concurrently enrolled, untreated
control group. Had the test regimen been inactive, a transmission
rate of 18.6% may have suggested some efficacy when compared with
historical data."
From the day Guay’s plane landed, her study began falling to
pieces. The system designed to keep the trial blinded immediately
collapsed. She reported this fundamental breakdown of control with
face-saving delicacy: "After randomisation, on-site study staff and
investigators became aware of the treatment and infection status of
the mother-baby pairs. Mothers also knew to what study group they
had been assigned after randomisation and were the infection status
of their babies during the study." She concluded: "Limitations of
our study were that investigators and mothers were not masked to
treatment status or outcome after randomisation." She could have put
it more plainly: ‘We fucked it up from the word go.’
That the unblinding of the trial would have affected its outcome
is certain, given the terror of the diagnoses and the inevitability
that at least some of the pregnant women given the news that their
babies might die would do anything to reduce the chances. Resort to
pill sharing between groups, for instance, or swallow other drugs by
the handful, or traditional potions, not necessarily benign. Those
on experimental nevirapine might have taken ‘proven effective’ AZT
as well. Unseen by the trial overseers, because "many doses [of AZT]
were given unobserved. Mothers were identified before labour and
given the drug to take at home." And one must consider the
possibility that those on old AZT might have gone to any lengths to
obtain the hyped new drug instead. The kind of stuff that FDA
inspectors discovered went on in the chaotic licensing trial that
preceded AZT approval in the US, and thereafter approval everywhere
else. The key one that became utterly corrupted (detailed in Just
say yes, Mr President: Mbeki and AIDS) but on the basis of which
GlaxoSmithKline still claims AZT extends lives. Being liars of Nazi
scale.
We recall that Guay originally had 1500 mother-baby pairs in
mind. Subjects for the study were drawn from pregnant "women
attending antenatal clinics at Mulago Hospital in Kampala,
Uganda…screened for HIV-1 infection by EIA [ELISA] for HIV-1
antibody. If a woman tested positive, she received post-test
counselling about her infection status and was informed about the
opportunity to enrol in HIVNET 012…" In other words, women lighting
up a single ELISA HIV antibody test were considered infected, told
so, and offered the chance to save their babies with free medicine
for them if they joined the drug trial. In her next sentence
however, Guay states that, "Women were eligible for the study if:
they…were positive on EIA and western blot for HIV-1 antibody…" So
which is it? By what criterion did Guay define HIV infection?
Nearly all ‘AIDS experts’ agree that a single reactive ELISA
antibody test is insufficiently reliable a basis upon which to make
an HIV-positive diagnosis – notwithstanding that the manufacturers
of these state-of-the-art, third-generation, recombinant
protein-based test kits typically claim 99.6 per cent specificity
for HIV, that is, only 4 mistaken positive diagnoses per thousand.
As the figure would suggest. It’s a claim made on an essentially
fraudulent basis however, because the sensitivity and specificity of
these tests has never been assessed by observing how they perform in
relation to groups of confirmed HIV-infected, as against confirmed
HIV-free individuals – HIV-infected meaning the virus isolated from
the HIV-positive patient’s blood or tissues. The reason is
startlingly simple. HIV has never, in the history of the AIDS era,
been isolated from anyone – by ultracentrifugal purification and
then electron photomicrograph verification (the standard procedure
for isolating viruses). The existence of the most feared pathogen in
history (suddenly with us, say ‘AIDS experts’) is inferred instead
from indirect ambiguous biochemical clues.
The Medical Underwriters Committee of the Life Offices
Association for our life insurance industry sees things differently.
They’re really with it, these guys. And just waiting to be cleaned
out in a ‘class action’ for damages for psychic shock. Its Informed
Consent form for folk like you and me taking a compulsory ‘AIDS
test’ for a life policy anticipates our question, "Is the test
always accurate? Can there be mistakes?", answering: "…the tests
used are very accurate." Underscored by: "What does it mean if the
test is positive?: …this means that you have been infected with the
AIDS virus." However when I taxed the pathologist drawing my own
blood about this, he disagreed with these statements on the form,
and claimed that pathologists had been conducting "a running battle
with the Life Offices Association for years" regarding the
sufficiency of a single ELISA test as a basis for an HIV-positive
diagnosis. But the machine just rolls on, as lives are crushed
daily. Who gives a damn when there’s money to be made, and certainly
none in rocking the boat? How many doctors do you know who have ever
taken a risky principled stand against abusive and harmful practices
of their profession? Or are likely to?
Guay’s Trial Profile schematic tells us that 13 839 women
were "tested for HIV-1." 2144 were described as: "…with positive
HIV-1 test." Whether Guay meant positive according to a single ELISA
– like the women just referred to – or positive according to an
ELISA ‘confirmed’ by western blot, is simply left in the air. We’re
left to wonder. 1499 of those 2144 women were excluded from the
trial, leaving just 645 mothers (not the 1500 intended). Among the
reasons for excluding the 1499, Guay mentions "an indeterminate or
negative western blot." But since women lighting up a single ELISA
"received post-test counselling about [their] infection status and
[were] informed about the opportunity to enrol in HIVNET 012", it’s
quite possible that some of these women came aboard the trial
without further testing. And since further testing always leads to
the exclusion of the majority of single ELISA positives, the
necessary conclusion is that most of these single ELISA positive
women were not infected. We are staring into a massive crack in the
trial’s foundations that nothing can patch.
Simple logic dictates that repeating an ELISA can’t confirm the
initial positive result, because whatever triggered the first test
(such as TB bacilli, and about 60 other documented conditions) can
just as well set off the second. Even if it’s made by a different
manufacturer. (This point has never occurred to University of Cape
Town ‘AIDS expert’ virologist Dianna Hardie, because according to
her, speaking on John Perlman’s prime-time AM Live radio show
("for the well-informed") on 4 April 2002, two positive ELISAs do
just fine.) Guay may or may not have been alive to the problem just
stated, because we see that she wasn’t content with a second
reactive ELISA: "We screened plasma from mothers for HIV-1 antibody
with a licenced assay (HIV type 1 Vironostika, Organon-Teknika…). If
the test was reactive, a second HIV-1 antibody test was done on the
same sample with the Murex 1+2 assay… For women with blood samples
that were reactive on both tests, we took a second sample and did an
HIV-1 western blot analysis (Cambridge Biotech…) for confirmation of
HIV-1 infection."
As your doubts begin rising like bile, you might wonder whether
those mothers ‘confirmed’ infected by western blot retesting were
really ‘living with HIV’ anyway. See, you can’t intelligently
confirm positive ELISAs with a western blot either. Most ‘AIDS
experts’ regard western blot results for HIV antibodies as decisive
– as the absolutely reliable last word. But not in England and
Wales, where western blots are not used to confirm positive ELISAs
precisely because they are regarded as too unreliable. (Hello?
Welcome to AIDS.) The spuriousness of a ‘confirmatory’ positive
western blot test for one or more positive ELISAs got a close look
in a lengthy landmark review, Is a positive western blot proof of
HIV infection? by Papadopulos-Eleopulos et al, published
in a prominent scientific journal, Bio/Technology (now
Nature Biotechnology), in June 1993, and it makes a staggering
read. (It’s archived on the Internet). It points out that all the
proteins used in these tests as antigens to fish for ‘HIV
antibodies’ are not unique bits of ‘HIV’ as had always been imagined
by ‘AIDS experts’, but are actually ubiquitous cellular proteins, or
clumps of them (oligomers). Bits of us, in other words, or bits of
common bugs. What’s more, the performance of the test has never been
gauged by reference to the gold standard of confirmed viral
infections. Because oddly enough, as mentioned, ‘HIV’ has never been
isolated. But we don’t have to get into all that. It’s surely enough
to know that ‘AIDS experts’ apply completely different criteria from
place to place when interpreting western blot results. In their
western blot paper, Papadopulos-Eleopulos and colleagues describe
eleven distinct currently applied official sets of criteria for
diagnosing HIV infection with western blot, varying radically from
continent to continent, institution to institution and even between
laboratories in the same city. So that whether you’re ‘infected’ or
not, and condemned by doctors to die soon, or told with relief that
you’ve a long life ahead, is really the luck of the draw. Being all
about how your test result is interpreted. Which criteria are
applied. Infected with a deadly virus here, but free of it according
to a different interpretation there. It’s unbelievable but true. But
as I say friends, this is AIDS, and in AIDS anything goes. Don’t
bother asking ‘AIDS experts’ about any of this stuff though, let
alone your family doctor. They’ll huff and puff with dismissals and
haughty assurances, but in truth won’t have a clue as to what you’re
even talking about. (Been there, got the tee shirt.) You’ll have to
read up for yourself.
By February 1998, only 49 women had been enrolled on Guay’s trial
– 19 of whom were assigned placebos, 15 AZT and 15 nevirapine – when
Shaffer’s pleasing report came through of the results of his
short-course AZT trial in Thailand (Lancet 353: 773-80). So
Guay thought the hell with placebos, and simply dropped the placebo
arm of her study. No doubt because she figured it would be unethical
to deny pregnant women antiretrovirals any longer. Although she
didn’t find anything morally troublesome about treating HIV-positive
pregnant women with the experimental drug, nevirapine. Before
calling off the placebo wing however, she noted that the
transmission rate among women given placebos was 26.1%. But also
that the rate among women given AZT was a "similar" 25%.
Amazing: when it comes to saving babies, placebos are as good as
AZT. But of course that’s not what the ‘AIDS experts’ tell you.
Being ‘AIDS experts’. Indeed, recording these substantially
identical numbers, Guay said in the same breath that "short-course
zidovudine may have had some benefit." Except that placebos wouldn’t
have caused the kind of toxic shock that resulted in the vomiting
and premature labour contractions that Guay reported among some of
the women given AZT. We’ll return to deal with her toxicity data
shortly.
Abandoning the placebo wing of the study made it impossible to
claim a benefit for the test drug – nevirapine being the new one
under investigation – since not only do untreated mother to child
transmission rates vary hugely from place to place according to all
the reports (ranging from approximately one in two cases to one in
ten) but even placebo administration has magical reported effects:
For instance in the Shaffer study of the effect of short-course AZT
administration on mother to child transmission, placebo
administration reduced ‘transmission’ at one hospital 14.3% and at
another 23.7%.
But not only does placebo administration have mysterious
benefits; so does taking nothing at all. A study by Ladner and Leroy
published in Journal of the Acquired Immune Deficiency Syndrome
and Human Retrovirology in 1998 (18:293-8) reported that the
transmission rate among 561 African women given neither
antiretroviral drugs nor placebos was 12%. That’s lower than the
13.1% rate triumphantly claimed by Guay as the benefit of
administering nevirapine. In short, the Ladner study provides
evidence for the contention that pregnant African women left to have
their babies unmolested by white missionary ‘AIDS experts’ like Guay
actually do best of all.
Apart from a theoretical grasp of some of the basics for the
proper conduct of a clinical drug trial – even as she watched her
study fall apart – Guay was wise to a couple more things. Like:
"…maternal viral load must be substantially decreased by the time of
labour or the baby must have systemic concentrations of active drug
present at the time of HIV-1 exposure to successfully lower risk of
transmission." But without batting an eyelid, she went on to report:
"Maternal plasma HIV-1 RNA levels were…not significantly different
at delivery from baseline." Which is kind of hard to reconcile with
her claim that the drug worked as hoped. To lower transmission risk
by lowering the concentration of viruses in the mother. Since it
turned out not to. Does anyone have any bright ideas?
We’ll just accept for now that a ‘viral load’ test result
indicates the number of HIV particles in your blood. We’ll block our
ears to Nobel Prize-winning biochemist Kary Mullis’s complaint that
it doesn’t, and that the test is an abuse of the PCR technology that
he conceived, for which he won the Swedish honour. (He wouldn’t know
what he’s talking about, right? He only invented the thing.)
With the effectiveness of nevirapine for the purpose of reducing
maternal ‘viral load’ in the can – Guay’s first condition for
efficacy – let’s turn to the second one: "…the baby must have
systemic concentrations of active drug present at the time of HIV-1
exposure to successfully lower risk of transmission." What she means
by a "systemic concentration" is enough of the drug in blood to
equal or exceed its inhibition concentration (IC50) – that is, a
concentration high enough to inhibit viral replication by half, as
determined by the usual indices. Guay whimsically picked a generous
figure of 100 ng/ml – ten times the IC50 of nevirapine asserted by
the manufacturer in 1990. Although two years later, other scientists
reported nevirapine’s IC50 value as being double that – both values
determined however in highly artificial laboratory conditions, with
no relevance to the real world whatsoever. Guay happily told us that
a pill of nevirapine given to pregnant mothers going into labour
achieved drug concentrations surpassing her arbitrary 100ng/ml
concentration. The trouble is that Havlir et al reported in
1995 (JID 171: 537-45) that in vivo (as opposed to
tricks in test tubes) the minimum concentration of nevirapine for a
virological response is 3.4 to 8m g/ml.
But in no case did the nevirapine plasma concentrations that Guay
achieved come anywhere even close to that. Meaning that with the
dose that she gave, Guay was unable to achieve systemic
concentrations of nevirapine in the babies sufficient to prevent HIV
replication and thereby reduce the risk of HIV transmission from
mother to child. Either before or during birth. Or after it during
breastfeeding. Which is another way of saying that nevirapine given
as described could not possibly be doing what Guay claimed it was.
But at the end of the study, Guay’s exciting bottom line was
this: The transmission rate (assessed at 14-16 weeks) among mothers
on AZT was 25.1%. On nevirapine it was 13.1%. On this basis,
nevirapine was declared 48% more effective than AZT. And Christ,
we’ve never heard the end of it.
Having heard ‘AIDS experts’ forswearing HIV antibody tests for
ascertaining mother to child transmission, since it’s accepted that
babies inherit their mothers’ antibodies when born, you would be
right to wonder how the "transmission rate" was determined.
Guay tells us: "HIV-1 infection [among babies] was defined as a
positive qualitative HIV-1 RNA assay confirmed by a quantitative
HIV-1 RNA assay or HIV-1 culture on a second blood sample. If babies
died after only one positive RNA assay on the sample, we classified
the baby as being infected." No matter what caused the baby’s death
– an adverse drug reaction, a bad heart, whatever. It’s a pity that
Guay never got around to reading the instruction manuals that came
with her PCR-based RNA test kits. Had she done so she would have
read Roche stating in regard to its qualitative RNA test used in her
study: "For research use only. Not for use in diagnostic
procedures." Not being reliable enough to hang a diagnosis on. Too
hit and miss. Our very own National Institute for Virology goes
along with the FDA about this. Such assays are hopelessly inaccurate
for HIV diagnosis – the US Centers for Disease Control agrees with
everyone. But inexplicably, without rhyme or reason – and unable to
explain why when asked – the CDC relaxes the rule for babies. For
them, the CDC says, they’re as true as an atomic clock. Sometimes:
When diagnosing babies putatively infected by their mothers – but
not by blood transfusions; in which latter case the CDC reverts to
its ban on RNA assays for diagnosing HIV infection in babies. Lovely
stuff.
If you’re not already gagging on the stench, here’s some rotten
cabbage to add: To confirm neonate HIV infection indicated by the
qualitative RNA test result, Guay tells us she used a quantitative
RNA test, commonly referred to as a ‘viral load’ test. But this is a
use of the assay explicitly forbidden by the manufacturer: "The
Roche Amplicor HIV-1 Monitor Test v1.5 is not intended to be used…as
a diagnostic test to confirm the presence of HIV-1 infection." But
hang on, we’re ‘AIDS experts’. Are you suggesting we’re illiterate
and incompetent morons?
In his answering affidavit to the TAC’s case for an order to
compel our government nevirapine case, the MCC’s Levin alluded
clumsily to some of the trouble with diagnosing babies with PCR
tests – in doing so, missing all their basic problems. On the use of
PCR for diagnosing babies, the statistician shared his wisdom with
us as follows: "It is also possible that the PCR test used at 6
weeks gave some false positives. A study by Glenda Gray on the
influence of breastfeeding on MTCT found a number of indeterminate
PCR results. A paper by Zijenah et. al., states that the use of PCR
for diagnosis of HIV infection has been hampered by a lack of
suitable primers for clade C viruses. In addition in September 2000
(after the Petra and SAINT PCR tests were done) Roche announced the
development of an improved PCR kit. Thus virologists should be
consulted to comment on the reliability of PCR particularly at 6-8
weeks." As if they’d know better than the manufacturer of such
tests. The fact is, all you have to do is read the instruction book
that comes with any PCR-based HIV-RNA assay. It says it all. You
cannot diagnose HIV infection with PCR tests. Period.
These most basic problems aside, let’s dwell for a moment on the
sense and wisdom of giving pregnant women nevirapine as they go into
labour to prevent mother to child transmission of HIV. A very
poisonous chemical, it’s well known. Even just a little bit, the FDA
warned doctors and nurses on 5 January 2001 – banning it for even a
couple of weeks of treatment in HIV needlestick injury prophylaxis.
‘AIDS experts’ tell us that unlike other viruses, HIV is a
retrovirus that burrows into and actually becomes part of our DNA.
That infected pregnant women can infect the babies they are
carrying. And that, according to Guay, a single pill of nevirapine
administered just before birth can prevent this. If the mother’s
virus has had nine months to reach the baby through the placenta,
the umbilical cord, and all those shared fluids, and thereafter
ingratiate itself into the baby’s DNA, would someone care to explain
the value of the magic pill? How it can possibly prevent anything?
Particularly since administration of nevirapine alone has no effect
on CD4 cell counts, and no significant effect on ‘HIV RNA’. Since
its putative activity is reverse transcriptase inhibition, the drug
is notionally only able to prevent the infection of new cells – not
eradicate HIV from already infected cells, or prevent such cells
from expressing new HIV particles. So if the child is ‘infected’ by
the mother while in utero during the nine months it is being
carried, administering nevirapine as she goes into labour is
completely pointless. As is giving it to the neonate: The drug
concentration in the neonate’s blood achieved by the recommended
dose of 2 mg/kg following birth is much lower than the concentration
determined to be necessary for an antiretroviral action, anyway.
Likewise the concentration of the drug found in breast milk, so it
can’t prevent infection via breastfeeding either.
But Guay claimed: "Most vertical transmission occurs during
active labour because of maternal blood transfusions to neonates
[?!] and direct exposure to virus during passage through the birth
canal [nasty place that – to ‘AIDS experts’]", citing a couple of
speculative studies proposing that mothers infect their babies
during labour and birth. Which makes it hard to understand why in
the West AZT is administered for many weeks before it. Especially
since it doesn’t reduce maternal ‘viral load’. British ‘AIDS
experts’ aren’t too sure about this last-minute stuff anyway.
Certainly not in all cases. In Reducing Mother to Child
Transmission of HIV in the United Kingdom, a report put out in
April 1998 by the Royal College of Paediatrics and Child Health,
hooked up with other top boffs, they state, "Indirect evidence
suggests that in the absence of breastfeeding about two thirds of
infections are acquired around the time of delivery."
We recall that the ostensible benefits of administering
nevirapine (per CD4 counts) were observed only in people
"with HIV infection who have experienced clinical and/or
immunological deterioration." But the overwhelming majority of
pregnant women who light up HIV antibody tests are healthy. (In fact
the Guay study excluded women with health problems.) And nobody
looks at whether their CD4 cell counts are within what ‘AIDS
experts’ consider (arbitrarily) to be within a normal range. What’s
more: "…nevirapine is only recommended for use in combination with
at least one other antiretroviral agent in the nucleoside analogue
class…" Because notwithstanding how allegedly "potent" it is (per
Boehringer Ingelheim’s The Role of Nevirapine in HIV Therapy
information release), the manufacturer admits that it’s ineffective
on its own no matter how much of it and for how long you take it.
Yet it is claimed by ‘AIDS experts’ to work its magic solo with a
single dose when given to pregnant women. Irrespective of their CD4
cell count or clinical health status. With perhaps one or two given
to the infant too. Brilliant.
In Mother to child transmission of HIV and its prevention with
AZT and nevirapine: a critical analysis of the evidence,
published as a monograph on 1 October 2001, Papadopulos-Eleopulos
and her colleagues point out another basic problem with giving
nevirapine to women entering labour. It takes an average of 4.6
hours for an oral dose of 200 mg to reach its maximum concentration
in the blood. Since women generally deliver at between 0.9 and 10.5
hours after dosing, and nevirapine takes between 1-8 hours to reach
maximum plasma concentration, an unascertained number must give
birth before the target concentration can be reached. In fact, as
we’ve discussed, it never is.
Nevirapine may be completely useless, but does it do any harm to
give it? I mean just to keep the AIDS activists happy. The doctors
full of high purpose. Saving babies’ lives. Mothers and children
always being a cuddly cause. Guay’s take on it was this: "Although
the zidovudine and nevirapine regimens we used seemed safe, long
term follow up of the babies remains a high priority to find out
about possible long-term toxic effects." But what did her data say?
About the immediate short-term ones? About the safety of the drugs?
About evidence of poisoning with the poisons?
Nevirapine, we read in Part One, is extremely toxic. Would it
come as a surprise then to learn that in HIVNET 006, the
toe-in-the-water trial that preceded the Guay study, a chilling four
babies out of the twenty-two treated with nevirapine died? Twelve
"serious adverse events" were reported, but the researchers
(including Guay) didn’t connect them with the drug. But then we’ve
read enough already to know that this bird wouldn’t recognize a
toxic reaction if it hit her between the eyes.
In Guay’s HIVNET 012 study "The rates of maternal serious adverse
events were similar in the two groups (4.4% in the zidovudine group,
4.7% in the nevirapine group). One mother in the zidovudine group
died 2 weeks after delivery and had bronchopneumonia. One serious
event, anaemia, was possibly associated with zidovudine, but
excessive blood loss at delivery may have accounted for the anaemia.
The occurrence of clinical or laboratory abnormalities in mothers
was similar in the two groups (82.2% in the zidovudine group and
80.7% in the nevirapine group had at least one such event). The most
frequent adverse clinical event was bacterial or viral infection,
occurring in 18.2% of women receiving zidovudine and 20.4% of those
receiving nevirapine, followed by parasitic infection in 12.4% and
15% respectively, followed by anaemia in 10.5% and 13.1%
respectively. Nine mothers (four in the zidovudine group, five in
the nevirapine group) had maculopapular rash, but no case was
serious." The "laboratory abnormalities" – at a sky-high rate –
detected after the drugs were given were not specified in the
report; Guay didn’t think it important to identify them. The
development of infectious illnesses in about one in five women on
the trial following ingestion of the general metabolic poisons
didn’t draw any comment either. Even though the FDA itself pointed
out in a press release on 5 March 1990 concerning AZT that it "may
reduce white blood cell counts to the point where the drug has to be
discontinued to avoid infections." Incredible.
As for the effect of the poisonous drugs on the babies, Guay
reported that, "The rate of serious adverse events in the two groups
[of babies] was similar up to the 18-month visit (19.8% in the
zidovudine group. 20.5% in the nevirapine group), with the median
age at last visit being 183 days… The most frequent cause of serious
adverse events within 56 days of birth were sepsis, pneumonia,
fever, congenital anomaly, asphyxia, and dyspnoea." 18 babies
suffered maculopapular rash, and 22 anaemia. "The frequency and
severity of laboratory-detected toxic effects, including neutropenia
[depleted immune cells], thrombocytopenia [depleted clotting
platelets], and abnormalities in creatinine [energy metabolism] or
bilrubin [breakdown product of haemoglobulin], were similar in the
two groups." But again, Guay didn’t think to share the numbers with
us. "38 babies (6.8%) died (22 (7.9%) in the zidovudine group, 16
(5.7%) in the nevirapine group). The most frequent causes of death
were pneumonia, followed by gastroenteritis, diarrhoea, dehydration
and sepsis."
On the basis of a one in five incidence of serious adverse events
and a seven per cent death rate among the babies treated with
nevirapine and AZT, would you also have deduced – especially without
placebo and untreated controls for comparison purposes – that
"zidovudine and nevirapine regimens…used seemed safe"? Being a
person in your right mind? In your sound and sober senses? Compos
mentis?
Following publication of the Guay study, South African AIDS
activists and journalists dropped AZT for pregnant women like a hot
plate. From now on the roar was for nevirapine. In every newspaper,
every day. John Perlman managed to cram in no less than three
interviews plugging nevirapine on his radio show one morning in
early 2002. Everyone joined in the feel-good campaign: Mandela,
Tutu, Jimmy Carter, Bill Gates, the lot. But it was only in only
South Africa that this unreal drive took off, like the great 1857
Xhosa cattle slaughter. Because American and European ‘AIDS experts’
didn’t see it the way the aforementioned nevirapine fans did – as
the ANC pointed out in a press release on 9 March 2002, deploring
Carter’s criticism of the government’s reservations about the drug,
after meeting Mbeki and Tshabalala-Msimang the day before, during
his tour with Bill Gates’s father to turn up the heat on the
government to give nevirapine to all HIV-positive pregnant women:
"We find it alarming that president Carter is willing to treat our
people as guinea pigs, in the interest of pharmaceutical companies,
which he would not do in his own country. We do not understand why
US citizens urge this drug upon us when the health authorities in
their own country do not allow its use for
mother-to-child-transmission. One of the reasons for this is that
these authorities say that there is insufficient data about issues
of the safety of the drug. For this, we do not need the interference
and contemptuous attitude of president Carter or anybody else. As
South Africans, we have the possibility to find solutions to our
problems, as the people of the US have. We are not arrogant to
presume that we know what the US should do to respond to its many
domestic challenges. Nobody from elsewhere in the world should
presume they have a superior right to tell us what to do with our
own challenges. We are therefore very surprised at the public
comments made by president Carter after this meeting." Carter hit
back from Kenya saying, "In most countries where presidents stand
aloof, the rate of infection continues to increase." In other words
Mbeki stands aloof, doesn’t care. But Kenyan President Arap Moi, he
said, has the right idea – having asked Kenyans in 2001 to abstain
from having sex for at least two years to combat AIDS: "It is often
not realised in Kenya the extraordinary leadership that President
Moi has taken in declaring several years ago that HIV is a national
disaster." Sure. Something new from doctors for us to shudder over,
since hardly any of us take the fire and brimstone of priests
seriously any more. As we admire the curves.
Hoping to cash in on the vast market opportunities generated by
the publication of Guay’s paper, Boehringer Ingelheim lodged an
application to the FDA for permission to market the drug in the US
for the new indication suggested by the study. It probably wished it
hadn’t. An audit of Guay’s data by researchers at the National
Institute of Allergy and Infectious Diseases (a branch of the
National Institutes of Health) found problems – described by FDA
spokesman Jason Brodsky as "potentially quite serious." As the
company put it in a press release on 22 March 2002: "Boehringer
Ingelheim is aware that questions have been raised regarding
reporting and documentation in a study conducted in Uganda for
prevention of the transmission of HIV from mother-to-child during
birth called HIVNET 012." NIAID’s simultaneous press statement put
it this way: "Although no evidence has been found that the
conclusions of HIVNET 012 (the Uganda trial) are invalid or that any
trial participants were placed at an increased risk of harm, certain
aspects of the collection of the primary data may not conform to FDA
regulatory requirements." This statement by the trial’s sponsor was
something of a snow job, having regard to NIAID’s John LaMontagne’s
disclosure that there were often "professional differences of
opinion" between the American researchers and the Ugandan hospital
staff concerning what constituted a "serious adverse event." The
"irregularities", as Reuters called them, appear to have concerned
in part the under-reporting of toxic reactions to the test drugs.
NIAD’s soft soap line cannot wash: LaMontagne’s revelation about
"differences of opinion" concerning the critical issue of toxic
reactions is indeed "evidence that the conclusions [of Guay’s study]
are invalid" – calling as they do the claimed safety of nevirapine
for babies very pertinently into question.
Anybody who hasn’t by now appreciated, in the light of our
discussion above, that ELISA and western blot test results for ‘HIV
antibodies’ are irrelevant, and who still wants to know whether the
women on the trial were single ELISA positive, or ‘confirmed’
positive with a second ELISA and a western blot, is in for a hard
time finding out. According to a report in the Kampala Monitor
on 3 April 2002, Guay’s Ugandan sidekick, Professor Francis Mmbiro,
had been able to find only 100 of the source documents that the FDA
wanted to audit; the rest, he said, were "stacked up in a container
due to the ongoing rehabilitation at the hospital." Sounds like lost
to me. To LaMontagne too, if you read between his lines: There are
"differences in the way hospitals in Uganda keep records and the
requirements of the FDA", which, he said, "quite rightly has a
rigorous standard." But this was a study conducted by American ‘AIDS
experts’. His attempt to blame the Ugandans for the shambles is
transparently dishonest.
The missing original case records also mean that we’ll never know
what happened to the Ugandan women who were single ELISA positive,
"received post-test counselling about [their] infection status and
[were] informed about the opportunity to enrol in HIVNET 012" but
chose not to. Were they were offered a second ELISA and then a
western blot? Or just packed home believing that they were
HIV-infected? To suffer under the false curse. Put on them by the
American doctors. In spooky white robes, dangling stethoscopes in
place of crucifixes.
The upshot of it was that Boehringer Ingelheim immediately
withdrew its application to the FDA for a licence to sell nevirapine
to pregnant women in the US. The drug is not currently licensed for
marketing to prevent mother to child HIV transmission in that
country or in Europe. But in developing countries it’s different:
Spokesman John Wecker said, "Boehringer Ingelheim continues to
donate nevirapine to programs in some 23 countries where the drug is
used to help prevent mother-to-child HIV transmission." That’s how
the company operates in penetrating new markets in the Third World:
It gives its drug away. Until such time as it becomes established by
usage as ‘the standard of care’. Then of course everything changes.
Do you think we’re in this for charity?
The striking frequency of severe toxic reactions in Guay’s study,
disclosed in the Lancet report – those that were actually
recorded – we have noted already. But the Treatment Action
Campaign’s activists evidently didn’t get as far as reading the
Adverse events and toxic effects bit on page 799. Because in
response to a contemporaneous public announcement by Health Minister
Tshabalala-Msimang concerning the reported trouble with the
integrity of the Guay study data, the TAC released a
characteristically histrionic press statement containing this gem:
"Not a single serious side-effect to mother or child has been
reported from this study."
The TAC statement went on: "In a speech today in Alexandria,
Johannesburg, the Minister of Health once more called into question
the safety and efficacy of nevirapine. Yet again she has done so
without any scientific basis. The inflammatory nature of her speech
and the continued baseless attacks on life-saving medicines that
have been proven safe and effective are highly irresponsible. This
is a desperate attempt to create smokescreens and red herrings to
divert public attention from her department's failure to accept the
Pretoria High Court's decision on mother-to-child transmission
prevention." But the Medicines Control Council took a different view
from that of the TAC’s drama queens. In a letter to
Tshabalala-Msimang it said, "We are to review nevirapine in the
light of these developments [the discovery by the NIH of
irregularities in the records of the study, and the consequent
withdrawal by Boehringer Ingelheim of its licensing application] and
will inform you of the decision as soon as information is
available."
Guay herself seems to have had some quiet doubts about her study.
Her modest intervention – safe she claims – would spare mothers and
babies in the First World the horrible AZT toxicities that have been
showing up in paper after paper in the medical journals, especially
the permanent foetal ones discussed in Debating AZT, and the
latest in Just say yes, Mr President. But Guay pulled back
from recommending nevirapine instead: "…we cannot judge the efficacy
of the nevirapine regimen used in our study compared with the full
three-part zidovudine regimen that is currently the standard for
prevention of transmission in more-developed countries. The data
from our trial do not change recommendations in the USA, Europe
for…use of the three-part zidovudine regimen for prevention of
transmission." Why not, if a pill or two of nevirapine was so
stunningly effective? And perfectly safe too. Why not?
Guay concluded the report of her study with some self-promoting
sales-spin: "Single-dose nevirapine given to the mother and the baby
is likely to be one of the few deliverable and sustainable
strategies for prevention of perinatal HIV-1 transmission in
resource-poor settings. The challenge is to rapidly translate our
findings into public-health policy to bring an effective HIV-1
intervention within the reach of millions of HIV-1 infected pregnant
women."
We see it differently, Laura. We think you should be struck off
for dangerous incompetence. And the identities of the anonymous
peer-reviewers who approved your pathetic paper for publication in
Lancet should be revealed, so that they can be publicly
shamed for doing so. Perhaps marched down the journal’s nearest high
street in dunce caps, along with those twenty-two "top names in
South Africa’s scientific and medical community" (reported by the
Cape Times on 22 March 2002), including Salim Abdool Karim,
Hoosen Coovadia, and Carolyn Williamson, who co-signed a
‘"declaration" published in Lancet in the same week to the
effect that "the fundamental scientific evidence in favour of
nevirapine is incontrovertible" and that the government should
accordingly "distribute the drug without delay." Joined in the
parade in the same hats we’d like to see nevirapine advocates like
Zachie Achmat, Nathan Geffen, Mark Heywood (they like marching),
Nicoli Nattrass, and the rest of the mediocrities who supported the
TAC's application to the High Court to force the government to
supply the drug, followed by Edwin Cameron, Costa Gazi, Glenda Gray,
James MacIntire and Mathew Cherish, along with Howard Barrell,
Belinda Beresford, John Perlman, Sally Burdett, Lynne Altenroxel and
the rest of their fellow white journalists who’ve had so much to
say, and who love getting righteously indignant in interviews and
articles, knocking recalcitrant black health officials who don’t
share their enthusiasm for giving cell-poisons to black babies. Not
forgetting former radical Catholic priest and struggle hero, Father
Cosmas Desmond – latterly a pharmaceutical industry pimp – who asked
in the Mail and Guardian on 8 March 2002: "Can Manto
Tshabalala-Msimang really be as abysmally stupid as her actions
suggest?" in view of her reservations about nevirapine toxicity in
the long term (shared by Guay), in the absence of any available
data. "In the meantime, the rather short-term effects of her – and
puppeteer-in-chief Thabo Mbeki's – policy of not providing the drug
to all HIV-positive pregnant women is killing tens of thousands of
babies every year."
The extraordinary thing about this popular notion is that there
is nothing in the medical literature to support the idea that babies
born to untreated mothers have a worse prospect of survival than
those treated. (Nor is there any good evidence for the root belief
among most whites that babies born to HIV-positive mothers are
doomed to an early death.) To the contrary, a host of recent studies
(canvassed in Debating AZT and Just say yes, Mr President)
show that babies exposed to these chemicals in utero have far
higher rates of death, disease, immunological disorders and ‘birth
defects’ than the unexposed. An unpalatable reality unfortunately,
but not a surprising one to folk who take the trouble to look at the
pharmacology of such drugs for themselves. Instead of asking the
doctor. Whose knowledge of such matters derives from what the
visiting bimbo from the drug company told him, or what he read in
the glossy advertisement on the inside cover of his professional
journal.
The real "challenge", we think, is to keep American ‘AIDS
experts’ like Laura Guay out of our country. And as far away from
our people as possible. We note that, "During screening for our
trial, many women refused to be counselled or tested or did not
return for their test results." Good on them! Spurning the doctors’
inherently ridiculous new dogmas, just as their ancestors drove out
missionaries along with their equally horrible ideas. Our local
‘AIDS experts’ and activists would do well to eat some humble pie
and return to basics, taking a tip from Socrates: "The only
good is knowledge and the only evil is ignorance." Bearing in mind
Will Rogers’s observation: "The trouble with ignorant people is not
what they don’t know; it’s that they know what ain’t." And Treatment
Action Campaign boss Zachie Achmat’s statement during an interview
in Rapport on 10 February 2002: "With great honesty the TAC
has always tried to understand medical science. And this is
something with which all South Africans have always struggled. We
are scientifically illiterate." Our impression exactly.
But not only of Zachie Achmat and his TAC. News of the FDA’s
scowl at the trouble with the Guay study data, and of our own MCC’s
in turn, sent the TAC into a flat spin. On 24 March 2002 it issued,
"FOR WIDEST DISTRIBUTION", Five Critical Statements on the Safety
and Efficacy of Nevirapine for Mother-to-Child Transmission
Prevention by the WHO, NIAD, CDC, Elizabeth Glazer Foundation
and Boehringer Ingelheim "that affirm the safety and efficacy of
nevirapine for the prevention of mother-to-child transmission." Not
one of them had picked up any of Guay’s study’s glaringly obvious
radical flaws.
The right thing to do, "with great honesty", would be for the TAC
to file a notice of withdrawal of opposition to the government’s
appeal against Judge Chris Botha’s nevirapine order, and for the
organisation’s patron, Supreme Court of Appeal Judge Edwin Cameron,
to take a tip from Alexander Pope – "A man should never be ashamed
to admit that he has been in the wrong, which is but saying, in
other words, that he is wiser today than he was yesterday" – and
issue a simultaneous public apology along the following lines:
‘We meant well but we were wrong: we weren’t thinking, we got
carried away, and we wasted everybody’s time. We uncritically
accepted a bad study and all the propaganda spun around it, and in
so doing, we endangered the lives and health of babies born to poor
black mothers in public hospitals. I would like to convey my
personal apologies to President Thabo Mbeki and Minister of Health
Dr Tshabalala-Msimang for having been at the forefront of local and
international condemnation of their well-justified concerns about
nevirapine. And about AZT too. I realize that by suggesting that
they have been both lacking in judgement and uncaring I have
needlessly besmirched their personal reputations, and indeed I have
damaged our whole country’s standing in the eyes of the
international community. I feel most embarrassed about the role I’ve
played in this fiasco, and particularly for having abused my status
as a senior judge to promote this harmful chemical, which I used to
believe was ‘a very good drug’. I’m really terribly sorry.’
Footnotes
For a comprehensive critique of Guay’s HIVNET 012
trial, see www.virusmyth.net/aids/perthgroup/nvp/.
It is crucial viewing for anybody with an opinion to state
concerning the merits of nevirapine for preventing mother to child
transmission of HIV. Part Four above should be considered as an
introduction only to some of the radical flaws in the Guay study.
Many more are detailed in the presentation – itself a summary, with
an expanded focus on nevirapine, of Mother to child transmission
of HIV and its prevention by AZT and nevirapine: A critical analysis
of the evidence, published as a stand-alone monograph on 1
October 2001. It can be ordered from Dr Valendar Turner, Consultant
Emergency Physician, Department of Emergency Medicine, Royal Perth
Hospital, GPO Box S1400, Perth WA 6845, Western Australia; <vturner@cyllene.uwa.edu.au>;
fax: 0961892243511.
The trouble with nevirapine will appear in
the appendices to the author’s new book in preparation, Just say
yes, Mr President: Mbeki and AIDS, a sequel and companion to
Debating AZT: Mbeki and the AIDS drug controversy, available
from good bookshops in South Africa, or from the author at cost if
not in stock. The text of the book is also posted on the Internet at
www.debating-azt.co.za and on the www.virusmyth.net and
www.aidsmyth.com websites.
Papadopulos-Eleopulos’s et al papers are
archived at www.virusmyth.net/aids/perthgroup/ and
www.leederville.aids. Their seminal AZT review, A Critical
Analysis of the Pharmacology of AZT and its Use in AIDS,
published in Current Medical Research and Opinion (1999)
Volume 15, Supplement 1, is archived by Librapharm online at:
www.librapharm.co.uk/cmro/vol_15/supplement/main.htm.
Appendix
DEBATING AZT: MBEKI AND THE AIDS DRUG CONTROVERSY
Foreword by Martin Welz
On 28 October 1999, after reading this debate, South African
President Thabo Mbeki ordered an enquiry into the safety of the AIDS
drug AZT. Now updated to reveal the President’s remarkable personal
involvement in the subsequent controversy, Debating AZT also
takes a critical look at the roles of rape survivor Charlene Smith,
Supreme Court of Appeal Judge Edwin Cameron, AIDS Law Project
director Mark Heywood, and Democratic Alliance leader Tony Leon.
Described by South Africa’s top investigative journalist, Martin
Welz, as "extraordinary", Debating AZT exposes the
dereliction of the medical experts and journalists on whom the South
African public has relied and provides the shocking facts.
JUST SAY YES, MR PRESIDENT: MBEKI AND AIDS
Foreword by xxxx xxxxx
What’s President Mbeki on about? He claims that "scientists don't
know what they are looking for when testing for HIV", talks about
AZT "triphosphorylation", and suggests that AIDS activists see
Africans as "promiscuous carriers of germs" and "human beings of a
lower order." Just say yes, Mr President explains. Relating
momentous developments in the medical, political and legal arenas
since the publication of Debating AZT at the close of 2000,
it sets out the author’s contacts with government, exposes the
prevarications of GlaxoSmithKline’s top officers, tells of the
American Food and Drug Administration’s endorsement of Mbeki’s
toxicity concerns, reports the considered responses of the ANC,
critically evaluates media cover of the controversy – notably by the
Mail and Guardian, rethinks the ‘Nkosi Johnson’ tragedy, has
a close look at Zachie Achmat and his Treatment Action Campaign, and
provides an extensive radical analysis of Supreme Court of Appeal
Judge Edwin Cameron’s "AIDS movement" – with staggering conclusions.
In doing so, it reveals the reasons for Mbeki’s wider doubts about
the integrity of AIDS medicine generally, and lays bare its
poisonous suppositions.
Just say yes, Mr President includes two scoops: It tells
the real story of how and why AZT was first synthesized in 1961 as
related by its inventor to the author for the first time, explodes
key claims about the pharmacology of AZT made by GlaxoSmithKline,
and provides a lethal critique of the popular AIDS drug nevirapine –
including the hitherto untold story of how the drug was forced
through the Canadian Therapeutic Products Agency under political
pressure after twice being rejected as unsafe and ineffective.
Book Reviews
Reviews of Debating AZT: Mbeki and the AIDS drug controversy:
"…the ravings of a drivelling conspiracy-theorist crackpot loony
fruitcake." David Beresford, columnist, the Mail and Guardian.
"Very good. Convinced me completely." Paul Foot, investigative
journalist, Private Eye and the Guardian, and author,
Words as Weapons.
"…you are justified in sounding a warning against the long-term
therapeutic use of AZT, or its use in pregnant women, because of its
demonstrated toxicity and side effects. … Your effort is a worthy
one… I hope you succeed in convincing your government not to make
AZT available..." Richard Beltz PhD, Professor of Biochemistry, Loma
Linda University School of Medicine, California, inventor of AZT in
the autumn of 1961.
"Deserves serious treatment. More strength to your arm." Donald
Woods, late former editor, Daily Despatch and author, Biko.
"I agree with (the alas late) Donald Woods: it needs much more
serious debate than big Pharma and the usual club of fringe
beneficiaries are permitting. There is simply too big a case to
answer, and it’s not being answered. Having said that, I suppose I
look a bit of a fool because I’m one of the numberless
well-intentioned people who has been championing cheapo
antiretrovirals for the Third World’s afflicted etc. But the book
worries me deeply, and, until the debate has been properly joined
and fought, will continue to do so. … Well done and good luck…" John
le Carré, novelist, The Constant Gardener.
"Absolutely amazing … a work of genius … he writes really well …
I just love his one-liners." Rian Malan, investigative journalist,
Rolling Stone, and author, My Traitor’s Heart.
"Anthony Brink is a man of many parts: magistrate or barrister by
day, musician by night…, prose stylist. Above all, dedicated and
fearless. …his book…is clear and crisp and his technical mastery
most impressive." Philip Johnson PhD, Professor of Law, University
of California at Berkeley.
"…extremely courageous. ... I thought I was beyond shockability
but [the book’s] revelations were stupefying. I think the marketing
of AZT to pregnant women is an obscenity." James Hogan, science
writer and science fiction novelist, The Legend that was Earth.
"Riveting… [The] style is very funny; it’s a shame the
subject-matter is so serious… Perhaps, after all, Thabo Mbeki is a
visionary, not the fiddling fool he’s made out to be… [If you are]
wondering what all the fuss is about, you will not find a more
forceful or persuasive explanation…than in this book. …meticulously
referenced, Debating AZT rattles the not-so-dusty medical
skeletons of Thalidomide, arsenic and mercury salts. It is a
remorseless denunciation of the first and most widely used anti-HIV
drug…" Don Bayley, former science editor of the Sunday
Independent and launch editor of the Independent Online.
"Absolutely spectacular … superb ... the definitive refutation."
Harvey Bialy PhD, editor at large, Nature Biotechnology,
and scholar in residence, Institute for Biotechnology,
University of Mexico.
"...excellent …the best, most comprehensive review on AZT
currently available..." Etienne de Harven MD, Emeritus Professor of
Pathology, University of Toronto, Canada.
"A hefty blow for free speech and against the strictures of
dogma… Crisp. Logical. Sometimes over the top. Bristlingly
intelligent. Exhausting. Acerbic. Sometimes vicious. For anyone who
wants to know what Mbeki’s on about, it’s all here, in a nutshell."
Yves Vanderhaeghen, deputy editor, the Natal Witness.
"…a rare combination of incisive insight, entertaining wit,
profound perspicacity, all of which and a lot more being available
through his racy, delicious pen. He exhibits the uncommon gift of a
timely turn of phrase that truly adds spice to the intellectual
content… Mr Brink’s book will have an Illichean impact likely to
cure the increasingly sick HIV-AIDS establishment in particular and
the medical and governmental establishments in general. His expose
is both a diagnosis and a cure… [It] will remain a classic
eye-opener to the misdeeds of modern medicine for decades to come. I
am also sure that Mr Illich will give his imprimatur to Mr Brink at
first reading." Manu Kothari PhD, Professor of Anatomy, Seth
Gordhandas Sunderdas Medical College, King Edward Memorial Hospital,
Mumbai, India.
"I started reading it the day it arrived, found it so fascinating
that I…read it through to the end that evening. A case of not being
able to put it down. Remarkable research and brilliant writing."
Jaine Roberts MA, researcher, HIV and Economic Health Research Unit,
University of Natal, Durban.
"[AZT: A Medicine from Hell] is a well written, lucid
article for anybody to read… your arguments about prescribing this
drug are excellent… Perhaps when more people like yourself who are
not scientists come out publicly to clarify the issue on this drug,
pregnant women will be spared! Your article will now be additional
prescribed reading for the students in my class." Shadrack Moephuli
PhD (toxicology), senior lecturer, Department of Biochemistry,
University of the Witwatersrand.
"…very nice writing … you can’t really be a lawyer … I love the
parallels with other past failed medical panaceas - calomel etc."
Denis Beckett, freelance journalist and filmmaker.
"What a good comprehensive review of the literature you
performed! … During my research I noticed a lot of resistance from
many different people to believe our data. In general there is
resistance to the ‘bad news’." Ofelia Olivero PhD, staff scientist,
US National Cancer Institute, USA.
"Christ this is good… Beautifully written… Extremely
accomplished… So much data. Makes the opposition’s platitudes look
embarrassingly hollow… Eleni and I think it’s really great."
Valendar Turner MD, consultant emergency physician, Department of
Emergency Medicine, Royal Perth Hospital, Perth, Western Australia.
"Anthony knows more about the science of this than all the other
AIDS dissidents put together. … It’s the way you write, it’s the way
you put it." Eleni Papadopulos-Eleopulos MSc, biophysicist,
Department of Medical Physics, Royal Perth Hospital, Perth, Western
Australia.
"Mind-blowing." Richard Stretch, attorney, Pietermaritzburg.
"A masterful piece." David Rasnick PhD, pharmaceutical biochemist
and patent holder, visiting scientist, University of California at
Berkeley, USA.
"…outstanding..." Hiram Caton PhD, Professor of Applied Ethics,
Griffith University, Brisbane, Australia.
"…wonderful … soldier on!" George Kent PhD, Professor of
Political Science, University of Hawaii, USA.
"…great… very important…" Stefan Lanka PhD, virologist, formerly
of the University of Konstanz, Germany.
"Enormously entertaining. …an outstanding piece of work ...
expert, trenchant devastation of AZT apologists." Neville
Hodgkinson, former medical correspondent, London Sunday Times, and
author, AIDS: The Failure of Contemporary Science.
"[AZT and Heavenly Remedies] is superb, extremely well
researched, analyzed, written… I could not have done a better job…
Are you a scientist or do you collaborate with one? How could you
survey so many scientific publications as an attorney? …Could you
publish your article or a variant of it in a medical/scientific
journal? It would strengthen our case no end, if scientific papers
of that quality would come from several sources, not only from
Berkeley and Perth ... I still can’t believe he wrote that. He’s
really a molecular biologist pretending to be a lawyer." Peter
Duesberg PhD, Professor of Molecular Biology, University of
California at Berkeley, USA.
"Amazing." Margarette Driscoll, senior features writer, London
Sunday Times.
"Every South African should read it. ... I couldn’t put it down."
Akash Bramdeo, television journalist, e-TV.
"My man, … you write your ASS off. ... Great, great stuff." Jon
Rappoport, investigative journalist and author, AIDS Inc.
"I laughed and I cried, I laughed and I cried." Hector
Gildemeister DPhil Oxon, molecular biologist, London.
"I read it at work pinned between my desk and my knees and
laughed until the tears rolled down my cheeks." Debbie-Ann Atkins,
office machinery sales representative.
"Humor kan soms ’n politieke daad van die ernstigste aard wees.
Niks is gevaarliker as om onaantasbare persone en instansies
belaglik te maak nie. … Wees gewaarsku – die boek het ’n vreemde
uitwerking op die leser. Enersyds laai dit iets ondraaglik swaar –
grotesk eintlik – op jou skouers, iets waarvan jy nie meer met
integriteit kan afkom nie. Andersyds moet jy nie verbaas wees as
daar na dese ’n glimlag aan jou lippe kom pluk elke keer as jy die
woord ‘AIDS expert’ hoor nie. … Die kersie op die koek – wat van
Debating AZT ’n meesterstuk maak – is die humor waarvan elke
reël, asook die spasies tussenin, deurtrek is. … Brink se styl – die
samespel van ligsinnige humor en dodelike erns – laat my byvoorbeeld
onwillekeurig dink aan die profetiese literatuur in die Bybel.
… Anthony Brink deins nie terug vir ‘lawsuits’ nie. Hy [skryf] in
die styl van meeslepende fiksie. Die boek is ’n taboebreker – nie in
die eerste plek omdat dit die taboe-gelaaide tema van VIGS in
Suid-Afrika aanvat nie – maar ook en veral omdat dit alle
genre-matige grense verontagsaam. Volgens die antropoloog Mary
Douglas het taboe te make met verskynsels wat dreig om gevestigde
klassifikasieskemas te ontwrig. Ook die outeur van hierdie boek is
in dié sin ’n taboeverskynsel: ’n advokaat uit KwaZulu-Natal wat met
innemende hubris die heilige teoretiese grond van die mediese
wetenskap betree. … Ek kan nie Debating AZT sterk genoeg
aanbeveel nie – of jy nou ’n literêre ervaring wil hê, boeiende
geskiedenis wil lees, meer te wete wil kom oor die VIGS-polemiek,
tot teologiese en filosofiese besinning gebring wil word, of sommer
net lekker wil lag. As ek die pous was (of ’n leidende
VIGS-navorser) sou ek die stempel van goedkeuring op hierdie boek
aangebring het: nihil obstat. Dit staan geskrywe. Niemand sal
ooit kan sê: ‘Ek het nie geweet nie ...’" Gerrit Brand, PhD
registrar, theologian, University of Utrecht, Netherlands.
The Treatment Action Campaign
An extract from the preface to Just say yes, Mr President:
Mbeki and AIDS:
The people who were honoured in the Bible were
the false prophets. It was the ones we call the prophets who were
jailed and driven into the desert, and so on.
Propaganda is to democracies what violence is
to dictatorships.
The duty of intellectuals is to tell the truth
and expose lies.
-- Noam Chomsky
[…]
Finally: South Africa faces particular perils posed by a hugely
influential and successful organisation of professional AIDS-drug
advocates, the Treatment Action Campaign. The effortless manner in
which the TAC pushed Merck around over fluconazole, mobilised public
opinion against the drug companies to shame them into abandoning
their case against our government over the importation of generic
drugs, and won a court order forcing the government to supply
nevirapine to HIV-positive pregnant women, are all testimonies to
its remarkable power and effectiveness. Led by a vanguard of
salaried cadres working full-time, it comprises a wider cohort of
volunteer activists and sympathisers in the public at large – 10 000
members, it claims. By positioning itself as a friend of the
victimised and of the poor, it has won massive support across a
range of constituencies, including the churches and the unions. Its
networks into the newspapers and pull over the media rival anything
we saw during apartheid, when politicians called the content of the
eight o’ clock news with a phone call.
As potent a coercive political force here as Jerry Falwell’s and
Pat Buchanan’s mobs are in the US, the TAC has developed a bully
pulpit from which it is calling the shots unchecked. On the most
cursory analysis of its agenda and campaigns however, the TAC is
hardly more than a lackey of the multinational pharmaceutical
industry. Moving the merchandise being their common purpose. Apart
from spats about how the industry’s largesse should be slushed about
by way of grants in the ‘Fight against AIDS’, the TAC’s only
significant quarrel with the pharmaceutical corporations concerns
pricing. For the rest, their relationship is as cozy as a bourgeois
marriage. It is symbiotic, and complimentary to perfection. TAC
lobbyists are incomparably more valuable to the industry than
conventional mercenaries hitting on politicians and journalists,
because unlike hired agents, the TAC genuinely believes in the goods
it sells for the industry by proxy, and consequently it evangelises
about them with the zeal of reborn Southern Baptists. It does this
because it believes all it’s been told. It really believes. The
industry just adores the TAC’s street marches because they make for
such potent propaganda. Free too. No amount of expensive advertising
can reach into the public mind and reap returns in product support
like even one TAC protest: ‘Gosh, Norma, those drugs sure must be
something. Look at how those people are always carrying on about
them.’
The promises held by the drugs that the TAC promotes are all
derived from what one might call official sources: the companies
themselves spinning marketing propaganda, other industry-sponsored
AIDS organisations, industry-sponsored treatment-information
clearing-houses, industry-sponsored researchers, and
industry-manipulated health bureaucracies such as the US Food and
Drug Administration, the Centers for Disease Control and the
National Institutes of Health. The history of how the said bodies
have lurched drunkenly on licensing, indication and dosing policy in
regard to AZT alone, just for a start, ought to generate scepticism
among informed people concerning the reliability of everything and
anything they officially advise. The TAC however, asks no questions
about the integrity of the information it receives from its approved
sources regarding the efficacy and safety of its favoured nostrums,
and is hostile to any suggestion that it might be corrupt, wanting,
or unsound – an pitiful display of worldly naivety to anyone with
even a passing acquaintance of the way the pharmaceutical industry
has historically prosecuted its business. We note here that in a
critique he wrote for the New York Nation on 9 April 2001,
John le Carré, in a breach of his usual measured English restraint,
referred to the world’s pharmaceutical corporations as the
"criminals of capitalism" – the burden of which soubriquet he’d
elaborated in the London Spectator four months earlier.
To the TAC on the other hand the pharmaceutical industry is not
the most egregiously venal enterprise of the global economy
(illustrations infra); it is Jesus handing out life-saving
loaves of wonder, Father Christmas with a big bag full of beneficent
goodies. Just a bit sharp on the costing.
It’s not hard to understand why. On 10 February 2002 Rapport
described TAC chief Zachie Achmat as the "meesterbrein"
behind the TAC. So when we read this "mastermind" in the Saturday
Star on 12 January 2002 referring to "Thabo Mbeki’s belief that
antiretrovirals like AZT are toxic and destroy the immune system",
as if they aren’t and they don’t, then we’re in serious trouble.
Because his organization wields tremendous power in our fledgling
democracy – the most telling proof of which has been the
substitution, by dint of a court order, of its own notions about an
appropriate drug intervention in place of our democratically chosen
government’s. Like the Third Reich however, we find that the TAC is
led by a prodigiously energetic but ignorant buffoon, driven by an
irrepressible sense of public purpose. To read the TAC’s press
releases and its ‘TAC Pledge’ is to be taken by how startlingly
puerile their choice of language, logical construction, syntax and
tone all are. With such intellectual stock at the TAC’s leadership
echelon, we can be certain that Achmat and fellow drug campaigners
have never cast a critical eye over any published research reports
concerning the vaunted benefits of their chemical darlings, much
less gone behind their happy conclusions to enquire into the quality
of their design, their conduct and execution, the quality of the
data gathered, and their interpretation – and whether on a cooler,
less interested analysis, the data gathered speak to anything like
the same benefits reported.
In campaigning for AZT and nevirapine, the TAC’s express charge
is that in health policy, the African National Congress in
government is a quisling to the poor, a betrayer of the black
proletarian insurrection. We care, says TAC chief Zachie Achmat, not
the party anymore: "…this is a government born from a party that
always fought for human rights. Now black people must hear: Your
lives are not worth anything." To appearances then, the TAC is a
militant left wing grassroots anti-establishment cell of urban
guerrillas – like Zapistas, defenders of the underprivileged,
pleading on their behalf to an uncaring government for a chance at
life. ‘We represent you now, not those sell-outs. We’ve taken over.’
In reality, the TAC is right up the pharmaceutical industry’s arse.
That the traditional left wing media, such as we have anymore, have
missed this, is beyond contempt. In my book anyway. So the Mail
and Guardian ("For people who think") takes an especially severe
flogging.
It’s my opinion that as a potent corporate agency, dressed up in
radical chic, the TAC has become a pernicious force in the life of
our new democracy, and it needs taking down. Best by deflation, I
reckon. So I mean to puncture it. With sharp facts garnished with
ample lashings of scorn. If feelings get bruised, too bad. This is a
serious matter. For many, of life and death. Death being a real
possibility for anyone who believes the TAC’s claims. And proceeds
to ingest the drugs it commends. As a colleague of mine discovered,
killed by a single month’s course of AZT and 3TC. Reduced, like
‘Nkosi Johnson’, to a skeleton in nappies. Also completely
incontinent, vomiting uncontrollably into a bucket. Also unable to
talk, his facial muscles paralysed, the rest of his muscles wasted
away. Unable able to pick himself off the floor when he fell. And so
forth. (See What’s the Hayman case all about? in the
appendices.) Judge Cameron ostentatiously conducts himself as the
TAC’s cheerleader and political patron. His status on the Appeal
Court bench imparts a credibility and legitimacy to the TAC agenda
that other non-governmental organisations can only dream of. I think
he has behaved deplorably irresponsibly. Turned to the light, his
very own utterances in his drug campaign cut him to pieces, like a
samurai pulling a hari kiri. As we’ll see. (A
butcher’s apron is advised.)
[…]
Anthony Brink is an Advocate of the High Court of South Africa.
Email: arbrink@iafrica.com.
The author of this article is a coauthor of Mother to child
transmission of HIV and its prevention with AZT and nevirapine: a
critical analysis of the evidence (#) published as a monograph on 1
October 2001, a copy of which is in the Presidential Library.
Minister of Health Dr Manto Tshabalala-Msimang also has a copy.
# Eleni Papadopulos-Eleopulos, Biophysicist, Department of
Medical Physics, Royal Perth Hospital, Perth, Western Australia;
Valendar F. Turner, Consultant Emergency Physician, Department of
Emergency Medicine, Royal Perth Hospital, Perth, Western Australia;
John M Papadimitriou, Professor of Pathology, University of Western
Australia, Perth, Western Australia; Helman Alfonso, Research
biologist, Department of Research, Universidad Metropolitana
Barranquilla, Colombia; Barry A. P. Page, Physicist, Department of
Medical Physics, Royal Perth Hospital, Perth, Western Australia;
David Causer, Physicist, Department of Medical Physics, Royal Perth
Hospital, Perth, Western Australia; Sam Mhlongo, Professor of Family
Medicine & Primary Health Care, Medical University of South Africa,
Johannesburg, South Africa; Christian Fiala, Gynaecologist,
Department of Obstetrics and Gynaecology, General Public Hospital,
Korneuburg, Austria; Todd Miller, Assistant scientist, Department of
Molecular and Cellular Pharmacology, University of Miami School of
Medicine, Florida, United States of America; Anthony Brink, Advocate
of the High Court of South Africa; Neville Hodgkinson, Science
writer, Oxford, England.
Acknowledgements
I thank: David Crowe in Calgary, Canada for procuring a
wad of confidential internal government memoranda by means I didn’t
care to ask, and for telefaxing them on to me, to enable me to write
Part Two; Vivienne Vermaak in Johannesburg for information from her
investigation notes for Part Three; and Eleni Papadopulos-Eleopulos
and Valendar Turner at Royal Perth Hospital for vetting Part One and
Part Four for scientific accuracy.