THE TROUBLE WITH NEVIRAPINE
By Anthony Brink
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.
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?
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.
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.
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.’
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; <email@example.com>; 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.
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.
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: firstname.lastname@example.org.
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.
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.