On 17 March 1999, my critical essay AZT: A Medicine from Hell was published in The Citizen, a daily newspaper distributed nationally in South Africa. Its sardonic tone and polemical style were contrived to stimulate a public debate of hitherto unexamined issues in the current controversy in South Africa concerning the provision of AZT to rape victims and HIV-positive pregnant women, for which AIDS activists, journalists, opposition politicians, doctors and health workers have been agitating strenuously.

South Africa’s leading AIDS authority, Dr Desmond Martin rose to the piece and mounted a rebuttal on 31 March entitled AZT: A Medicine from Heaven.

My rejoinder AZT and Heavenly Remedies was printed the following day. It has since been substantially revised, extended and updated, and includes mention of several papers appearing in the journals Clinical Infectious Diseases, New England Journal of Medicine, Nature Medicine, AIDS, the Journal of Medical Virology, The Lancet, Mutation Research, the Journal of the American Medical Association and Current Medical Research and Opinion between April and September 1999.

Dr Martin’s off-topic contentions are addressed in an appendix to my reply, available on request.

At my instance, NOSEWEEK - edited and published by South Africa’s most accomplished and respected investigative journalist, Martin Welz - will be covering AZT in a forthcoming edition, according to notices appearing in both its November 1998 and May 1999 issues.

ANTHONY BRINK

Pietermaritzburg

South Africa

Human Immunodeficiency Virus (HIV) disease is a major global health problem and is associated with a significant morbidity and mortality.

The number of people infected with HIV is rapidly increasing; recent estimates indicate more than 30 million adults and 1,1 million children are infected worldwide. In South Africa it is estimated that in excess of three million people are infected. It has been predicted that 40 million persons, including four to five million children, will have acquired the infection by the year 2000. Mother-to-child transmission, the major cause of HIV infection in infants, has led to a 30 percent increase in the mortality rate of infants and children in recent years.

The introduction of highly active anti-retroviral therapy (HAART) has been good news. In the US the age-adjusted death rate among people with HIV in 1997 was less than 40 percent of what it was in 1995. This experienced was mirrored in other Western nations where dramatic declines in morbidity and mortality as a result of the increasing use of combination anti-retroviral therapy has occurred; many of these regimens contain AZT.

When AZT and other nucleoside analogues were first introduced they were used as monotherapy (a single drug was used). Clinical experience quickly showed that the effect of a single drug was short-lived, as resistance to the drug developed. It was then shown that by using a combination of drugs, a more lasting effect was obtained.

An added advantage of combination therapy was that the drugs acted at different stages of the replication cycle of the virus. This option therefore made sense; the risk of drug resistance was drastically reduced and long-lasting beneficial effects have been recorded. AZT together with 3TC and a protease inhibitor is a combination that has been found to be highly effective.

Impaired quality of life associated with the progression of HIV disease has a profound effect on the patient and leads to an increase in the direct medical and non-medical costs of illness. Published studies have shown that patients on combination therapy with AZT and 3TC have been able to maintain or more importantly improve their quality of life.

So effective are combination anti-retroviral regimens in reducing the complications of the disease that there are anecdotal reports emanating from the US that Aids wards are being emptied of their patients and in some instances wards have been closed. Clinicians are now treating patients in out-patient settings and the status of the disease has changed to that of a chronic manageable disease.

It is however, in the arena of prevention of HIV infection that AZT has produced dramatic results.

Worldwide, approximately 500 000 infants become infected each year as a result of mother-to-child transmission. In some African countries 25 percent of pregnant women are infected with HIV. Without preventative therapy up to a third of their babies may become infected; many of these children will die in their early years.

In 1994 a clinical trial conducted in the US and France (ACTG 076) demonstrated that AZT given to mothers during their pregnancies, intravenously during labour and orally to their babies for six weeks reduced the risk of mother-to-child transmission by 67 percent. This regimen has been adopted as the "standard of care" in the US.

However, it is unsuitable for developing countries because of its complexity and cost.

To address the problem the Ministry of Health in Thailand introduced a trial of simpler and less expensive regimens of AZT to prevent mother-to-child transmission. This trial showed that a simpler regimen of AZT given orally to mothers in the last weeks of pregnancy reduced the risk of transmission by 50 percent. This short course AZT regimen (so-called Thailand regimen) is much more suitable for developing countries than the US-protocol because it is much easier to administer and less costly ($50 v $800).

Preliminary data from United Nation Aids Programme (UNAids)- sponsored studies have also demonstrated that even more abbreviated, affordable, AZT-containing regimens may be equally effective.

Another instance where preventative AZT therapy is commonly used is in the event of a health-care worker (HCW) sustaining an occupational exposure to blood or body fluids from an HIV infected person (eg. needle-stick injury).

These occurrences are usually charged with much emotion and HCW's are, quite justifiably, entitled to appropriate post-exposure prophylaxis to be commenced as soon as possible after the injury. A multinational study conducted among occupationally exposed HCW's demonstrated a 79 percent reduction in the risk of acquiring HIV infection when AZT was used as post-exposure prophylaxis.

The toxicity of AZT is a very real issue however, the toxicity (particularly bone marrow toxicity) is usually noted in patients with advanced HIV disease whose bone marrow function may already be impaired by HIV disease. Toxicity does not appear to be a problem during short-term use (post exposure prophylaxis or mother-to-child transmission prevention).

Nevertheless vigilance and monitoring on the part of the clinician is necessary. If toxicity occurs the drug should be stopped and other drugs substituted and any appropriate management should occur. Toxicity in most cases is reversible. In addition, careful monitoring of babies whose mothers took AZT during pregnancy has failed to show any significant abnormal findings.

Thus AZT in combination with other drugs has proved to be invaluable for the treatment of those already infected with HIV and has also proved to be a potent preventative agent in the mother-to-child setting and for occupational exposures. For these very reasons the drug AZT deserves the accolade : AZT: a medicine from heaven.

Note: Dr Martin has no conflict of interest and has not received financial sponsorship from Glaxo-Wellcome.

Winston Smith, in Nineteen Eighty-Four

George Orwell

AZT - pure poison? Nonsense, retorts Dr Martin, with the avuncular bedside reassurance of Doctor who knows best. AZT, he proclaims, is God’s own medicine.

In his letter covering his response to my essay AZT: A Medicine from Hell, Martin rebukes the editor of The Citizen for his "gross irresponsibility" in publishing my piece without first having obtained the views of "the established experts." In this reply, we’ll have a look at what experts from the top drawer of the AIDS research establishment have to say about AZT, the kind of guys who get to publish in the world’s most splendid medical and scientific journals.

True believer that he is, Martin sonorously praises "Highly Active Anti-retroviral Therapy" (HAART - cocktails of AZT and other metabolic poisons) as "good news" and "highly effective", and even reports mass Lazarus cures with entire hospital wards closing down. Really? Not according to big-time AIDS clinician Dr Michael Saag of the University of Alabama, coeditor of ‘cutting-edge’ tome AIDS Therapy just published in January. No dissident, he’s a paid consultant for AZT manufacturer Glaxo-Wellcome and other pharmaceutical corporations. In an interview in Esquire in April, he confesses that the HAART "'dam' is already leaking; there’s high danger of it collapsing altogether. Failures are occurring right and left." He states plainly that doctors "should expect failure with whatever (HAART cocktail they) first use. We should plan on it. We should prepare for it. Clinicians should expect failure." And failure they get.

Carr and Cooper wrote in The Lancet in December last year: "As the evanescent blush of success with so-called highly active antiretroviral therapy regimens begins to recede into the darkness…post-1996 AIDS conference hype (about) combination therapy including a protease inhibitor…(has come) back to haunt us."

In April in the journal AIDS, Dr Steven Deeks and his colleagues at San Francisco General Hospital and the University of California, reported treatment failure for more than half their AIDS patients given HAART ‘triple-therapy’. Similarly, Medical Professor Dr Julio Montaner, head of AIDS Research at St Paul’s Hospital/University of British Columbia, Vancouver, and co-director of the Canadian HIV Trials Network tells us in the May issue of the Journal of the American Medical Association that, "Given the complexities and the increasingly recognized potential for long-term adverse effects of many of the currently available treatments, it is hardly surprising that (for) an alarmingly high proportion of patients…the failure (rate) has been in the order of 30% to 50% of patients at 1 year…"

Several other research papers published about AZT-based HAART in May and June all point a thumbs-down:

In May, in the New England Journal of Medicine, Zhang et al at the Aaron Diamond AIDS Research Center in New York report that following combination antiretroviral therapy "replication-competent virus can still be recovered from latently infected resting memory CD4 lymphocytes; this finding raises serious doubts about whether antiviral treatment can eradicate HIV-1… Six of the eight patients had no significant variations in proviral sequences during treatment…(and) it may require many years of effective antiretroviral treatment to eliminate HIV-1." The researchers fret: "We are unable…to explain why drug-sensitive HIV-1 is capable of replicating at low levels during treatment with three or four drugs. But it is essential to the therapeutic effort that the answer, be it pharmacokinetic or cellular in nature, be obtained promptly." Furtado and colleagues of the Northwestern University School of Medicine in Chicago and Los Alamos National Laboratory in New Mexico, reporting their research findings in the same issue, don’t beat about the bush so much: "HIV-1 infection cannot be eradicated with current treatments." And Harrigan et al at St. Paul’s Hospital in Vancouver, British Columbia report in AIDS in May that in six patients with undetectable viral loads who gave up HAART "because of lipodystrophy, narcotic overdose, insomnia, and/or high blood pressure," all experienced "HIV rebound…within 6 to 15 days…and approached or exceeded pretherapy (plasma HIV RNA) levels…within 21 days of stopping therapy."

Commenting on these dismal findings, AIDS boss Anthony Fauci, Director of the National Institute of Allergies and Infectious Diseases in the US concedes with his characteristic up-beat gloss on yet another broken therapeutic promise, "What all these studies underscore is the pressing need to develop more effective, less toxic medications that can be used over the long term to suppress HIV, as well as novel strategies to then purge residual virus from the body and boost the immune system." In plain English, this translates to an urgent need to find alternatives to AZT-cocktails because they are too poisonous and too ineffective to justify continued use.

In Nature Medicine in May, two other papers document how useless and harmful AZT-based ‘triple-therapy’ is. The first by Finzi et al at Johns Hopkins University Medical School tells the "depressing news" that "resting T-cells" said to be infected by HIV are impervious to HAART and appear to need a lifetime’s uninterrupted treatment - a regimen which the researchers point out is not feasible due to its toxicity. The second paper by Picker et al of the University of Texas Southwestern Medical Center suggests that patients on HAART need to take "vacations" from such medicine periodically, in view of their finding that HAART itself causes a reduction in their patients’ T-cell counts, and that patients suffer a significantly weakened immune capacity after such treatment. And in the May issue of AIDS, Ibanez et al at the Fundació irsiCaixa, Retrovirology Laboratory, Hospital Universitari Germans Trias i Pujol, in Barcelona, Spain report their findings "that 48 weeks of HAART does not significantly reduce the integrated HIV-1 proviral DNA load in the latently infected CD4 T cell reservoir." In July, an article in The Lancet mentions a disappointing study just reported in Annals of Internal Medicine by Lucas et al at Johns Hopkins University School of Medicine. Of 273 patients given HAART over a two year period, only "23% of the cohort had fewer than 500 copies/mL HIV1 RNA in all three time intervals" during the trial.

Commenting ruefully on the Finzi and Zhang studies in the June issue of Nature Medicine, Saag and his colleague Michael Kilby at the AIDS Clinical Trials Unit, University of Alabama rub in the rude fact that HAART doesn’t work: "As (Zhang et al have) suggested, immediate attention should focus on the reasons why three- and four-drug potent anti-retroviral therapy does not completely suppress virus replication…even in the presence of undetectable HIV plasma RNA levels."

In July The Lancet mentions a disappointing study just reported in Annals of Internal Medicine by Lucas et al at Johns Hopkins University School of Medicine. Of 273 patients given HAART over a two year period, only "23% of the cohort had fewer than 500 copies/mL HIV1 RNA in all three time intervals" during the trial.

AZT-based HAART has been said to prevent new rounds of infection by stopping HIV DNA from producing HIV RNA and thence the proteins and particles which AIDS experts identify as HIV. Since these latest research findings reveal that during HAART, the HIV viral burden - the amount of DNA provirus - does not alter, the "established experts" are confronted with small choice in rotten apples: either HAART isn’t anti-retroviral, or there is no relationship between HIV DNA and HIV RNA (which runs counter to a fundamental notion in the HIV theory of AIDS), or all that these cyto-toxic drugs do is hinder cells making RNA of any kind, or perhaps they just interfere in the measurement of whatever RNAs there are. Or all of the above. Take your lucky pick.

Current HAART research reports are reminiscent of the Pellagra plague in the US South over the first four decades of this century, for which Fowler’s Solution (arsenic) was the drug of choice. Heaps of impressive research articles were published in the medical journals regarding treatments for the germs causing this terrible disease, which affected millions and caused people to die in droves. It turned out the experts were all barking up the wrong tree. Everyone now knows that Pellagra is a disease of nutritional deficiency, and has nothing to do with germs. Pity about the quarantined patients in dozens of specially built pellagrin-hospitals who died of arsenic poisoning before the experts eventually changed their minds.

Writing in AIDS in 1997, Kelleher et al noted, "Lack of strong evidence exists for sustained immune reconstitution by current therapies (comprising AZT and other drugs, and AZT may) unmask silent opportunistic infections." Like PCP. Pneumocystitis carinii pneumonia is a scarce disease, very difficult to diagnose accurately. It is caused by a ubiquitous fungal germ in just about all of our lungs. As a rule it only takes over, often together with esophageal candidiasis (a related fungal infestation), when harmful chemicals create the opportunity. Tracts of tissue in these moist regions, poisoned by heavy antibiotic use, poppers (amyl nitrite) inhalation, cancer chemotherapy, or AZT (about which more below), become the seedbeds for these fungi to thrive, like green mould on damp bread. Doubters might wonder why in South Africa, only the rich who can afford AZT - alone, or as the basis of triple-therapy cocktails - develop PCP. Not penurious blacks, the overwhelming majority of HIV-positives here, both proportionately and in gross numerical terms. Their ‘AIDS indicator diseases’, if they ever develop, are the dull sicknesses that the poor in Africa have always endured. Nothing exotic like PCP.

Not only can AZT "unmask silent opportunistic infections", it can exacerbate clinically conspicuous ones. Havlir and Barnes reported in February in the New England Journal of Medicine that HIV-positive Tuberculosis patients treated with (AZT-based) ‘antiretroviral therapy’ developed "paradoxical worsening of disease…in up to 36 percent of (them), characterized by fever, worsening chest infiltrates on radiograph, and peripheral and mediastinal lymphadenopathy…(whereas) only 7 percent of patients who received antituberculosis therapy but not antiretroviral therapy had paradoxical reactions."

In the Esquire article, Saag complains that the death rate of his patients on combinations of AZT, its chemical cousins like 3TC and ddI, and protease inhibitors is on the rise: "They aren’t dying of a traditionally defined AIDS illness," he says. "I don’t know what they’re dying of, but they are dying. They’re just wasting and dying." Could it be that cell-poisons poison cells? But such myopia is par for AIDS doctors who learn their trade by rote. And from drug advertisements. Of course the thought that Saag is killing his patients with his sponsors’ drugs is probably too awful to entertain. "It is sobering;" Saag continues, "while we are making good guesses, they are just guesses. We don’t know what we are doing." It’s hard to disagree. How good the treatment guesses are was revealed during an interview by Ted Koppel on Nightline on 19 May. Saag admitted that "unfortunately, right now, the roller coaster is headed back downhill. And it’s not really clear how far down it’s going to go, but the momentum right now is certainly in the wrong direction."

US AIDS treatment specialist Dr Joseph Jemsek is more forthright. On 8 January, he was interviewed on the ABC television news show 20/20:

Q: And…in addition, the drugs themselves could kill her by damaging her heart, liver, her pancreas.

JJ: The drugs aren’t perfect. They cause side effects, which are cumulative and inexorable. Now I’m starting to see people die again.

Q: So people are actually dying of the side effects of these...

JJ: Yes, you’re...

Q: …anti-viral drugs?

JJ: Yes, you’re starting to see that.

Martin’s happy claim that AZT cocktails afford "long-lasting beneficial effects" was refuted in November 1997, when Lemp et al reported in the Journal of Acquired Immune Deficiency Syndrome and Human Retrovirology that with HAART, "the treatment benefit is temporary and confers no long-term survival advantages." Obviously. How could it possibly? Would you nurse your wilting pot-plant with weed-killer? In the clever age, whatever happened to common sense? At last some lay folk are waking up; Steven Gendin wrote an article in the January issue of AIDS-drugs-promoting rag POZ, candidly entitled, "If the virus doesn’t get you, the drugs you take will." He’s seen enough of his friends fade away on AZT to know.

That AZT, the mainstay of HAART, is entirely ineffective as a therapy was borne out clearly by the large-scale Concorde trials in Europe, reported in The Lancet in April 1994. Embarrassingly for Glaxo-Wellcome, and disastrously for its share prices, the fabulous results of the chaotic American study that had preceded FDA approval of AZT couldn’t be reproduced. Glaxo-Wellcome’s representatives on the trial’s coordinating committee refused to sign the report. Understandably - they could hardly endorse a finding that their flagship money-spinner didn’t live up to its billing. (Its demonstrated therapeutic irrelevance led to AZT’s employment as a drug combined with others - all equally ineffective on their own, as if to mix three toxic duds would be to conjure them miraculously into a medicinal marvel.) In fact not only was AZT found to be useless at the end of the Concorde trials, it was found to be positively harmful: Phillips et al reported in a letter to the New England Journal of Medicine in March 1997 that, "Extended follow-up of patients in one (AZT) trial, the Concorde study, has shown a significantly increased risk of death among the patients treated early." (Another important finding by the trial’s overseers was that CD4 cell counting was a waste of time, and bore no relation to clinical health. Emphasizing the worthlessness of the practice in Annals of Internal Medicine in 1996, Fleming and DeMets described it as being "as uninformative (an indication of immune status) as a toss of a coin." Not that anyone took any notice. Today, patients terrified by their doctors’ mournful announcements of their low cell counts - still taken as a signal of collapsing health and imminent demise - are inspired to start with ‘antiretrovirals’, following which the prophesy will be faithfully fulfilled.)

Here are some of AZT’s ‘side-effects’ listed by its manufacturer: Body as a Whole: abdominal pain, back pain, body odor, chest pain, chills, edema of the lip, fever, flu syndrome, hyperalgesia; Cardiovascular: syncope, vasodilation; Gastrointestinal: bleeding gums, constipation, diarrhea, dysphagia, edema of the tongue, eructation, flatulence, mouth ulcer, rectal hemorrhage; Haemic and Lymphatic: lymphadenopathy; Musculoskeletal: arthralgia, muscle spasm, tremor, twitch; Nervous: anxiety, confusion, depression, dizziness, emotional lability, loss of mental acuity, nervousness, paresthesia, somnolence, vertigo; Respiratory: cough, dyspnea, epistaxis, hoarseness, pharyngitis, rhinitis, sinusitis; Skin: acne, changes in skin and nail pigmentation, pruritus, rash, sweat, urticaria; Special senses: amblyopia, hearing loss, photophobia, taste perversion; Urogenital: dysuria, polyuria, urinary frequency, urinary hesitancy.

In truth, AZT makes you feel like you’re dying. That’s because on AZT you are. How can a deadly cell-toxin conceivably make you feel better as it finishes you, by stopping your cells from dividing, by ending the vital process that distinguishes living things from dead things? Not for nothing does AZT come with a skull and cross-bones label when packaged for laboratory use. Here’s a typical experience of AZT; last year in September, several newspapers in the US and Canada ran a story KIDS WITH AIDS by Gayle Melvin: "Robert Swanson’s medicines came with horrible side-effects: nausea, diarrhea and blinding headaches… Robert would secretly skip a dose of medicine. ‘I’d find his pills all over the place, in his room, in the dirty clothes’, Britten says… ‘When you think of medicine, you think of something that makes you better, but I don’t feel better when I take it,’ Robert says. ‘I’d rather feel good and let the virus take over than feel bad and take the medicine.’ …Tina (takes) AZT,…ddC and Viracept, a protease inhibitor…three times a day. Then she waits to get sick. ‘My head will start to hurt all over, like a pounding. I get dizzy. Sometimes I throw up,’ she says in her sweet, girlish voice. She gets sick every time? ‘Every time’, says Tina… As they go through their teens, these children face (the) challenges (of) taking responsibility for their…often debilitating medical regimen."

For an early clinical report of AZT poisoning: Dr Laura Bessen and her colleagues wrote a letter to the New England Journal of Medicine in March 1988 headed, Severe Polymyositis-like Syndrome Associated With Zidovudine Therapy of AIDS and ARC. They reported, "All patients had an insidious onset of myalgias, muscle tenderness, weakness, and severe muscle atrophy favouring the proximal muscle groups. Physical examinations revealed varying degrees of muscle weakness and grossly apparent atrophy. Weight loss due to muscle loss was uniformly noted; in one patient, the loss was a striking 18kg." (A colleague of mine treated with AZT went this way. After just two months of AZT treatment, he lost most of his muscle mass, and died weighing 40kg.) Besson et al noted, "We did not observe this illness before zidovudine was available…" It sure wasn’t the HIV, because the doctors found that "the syndrome was ameliorated after the drug was stopped."

Besson and her colleagues’ clinical observations were investigated and reported by Dalakas et al in 1990 in the New England Journal of Medicine. Comparing the myopathy (muscle wasting) caused by AZT with that presumed to be caused by HIV, they concluded that "long-term therapy with zidovudine can cause a toxic mitochondrial myopathy, which...is indistinguishable from the myopathy associated with primary HIV infection... Before 1986, when zidovudine (formerly called azidothymidine) was introduced, the number of patients with HIV-associated myopathy was small, and myopathy was considered a rare complication of HIV infection. During the past two years, an increasing number of patients receiving long-term zidovudine therapy have had myopathic symptoms such as myalgia (in up to 8 percent of patients), elevated serum creatine kinase levels (in up to 15 percent), and muscle weakness. These symptoms generally improve when zidovudine is discontinued." Whether muscle wasting ever occurs among HIV-positives who avoid AZT and related drugs is doubtful: Coker et al reported in AIDS in 1991, "A clinically significant myopathy that precedes the development of zidovudine associated mitochondrial myopathy has been a rarity in our experience."

In 1991, in Neuromuscular Disorders, Chariot and Gherardi reported, "Long term therapy with (AZT) can induce a toxic myopathy associated with mitochondrial changes." Looking into biochemical mechanisms to account for the toxicity of AZT for mitochondrial DNA, Hayakawa et al reported their study of mice given AZT, in the journal Biochemical and Biophysical Research Communications in 1991. They proposed "oxygen damage of mitochondrial DNA (to be) the primary cause of mitochondrial myopathy with AZT therapy (and emphasized that) it is urgently necessary to develop a remedy substituting this toxic substance, AZT." The burden of these reports is plain: AZT rots your muscles. As it does so, the patient enjoys Martin’s "quality of life" as he inexorably slips away with the wasted appearance of an extermination-camp victim. AIDS then goes onto the death certificate, and the image of the white AIDS patient who horribly and mysteriously wastes away is reinforced in the popular consciousness, another AIDS case to chalk up to the statistical tally. (No one cared much about wasting in Africa, commonplace from time immemorial where poverty-linked tuberculosis, malaria and gut diseases are endemic, until its opportunities for research grants popped up when it was renamed ‘slim disease’ or AIDS.)

In his reply to my essay, Martin admits that AZT destroys bone marrow, but then hedges: HIV "may" be the real culprit. This is a tired old tale rehashed. Mercury and arsenic salts - doctors’ favourites for ages - poisoned the patient, whose death was then blamed on unbalanced humours or germs. That AZT destroys bone marrow is frankly declared by its manufacturer. So let’s not fudge. In 1987 Parkash reported in Annals of Internal Medicine, "Four patients with the acquired immunodeficiency syndrome, and a history of Pneumocystis carinii pneumonia developed severe pancytopenia 12 to 17 weeks after the initiation of azidothymidine therapy. Partial bone marrow recovery was documented within 4 to 5 weeks (after discontinuation of AZT) in three patients, but no marrow recovery has yet occurred in one patient during the more than 6 months since AZT treatment was discontinued." For AIDS doctors slow to the point, Dainiak et al spell it out in their 1988 paper in the British Journal of Haematology, entitled, 3’-Azido-3’-deoxythymidine inhibits proliferation in vitro of human haematopoietic progenitor cells. They reported, "Anaemia (during AZT therapy) appears to be due to bone marrow suppression." Consistent with this, Costello reported in the same year, in the Journal of Clinical Pathology that, "Blood transfusion is often necessary in patients with AIDS, especially in those receiving AZT, a drug which produces severe anaemia in a proportion of recipients. Forty nine (36%) of 138 patients treated with AZT required blood transfusion at least once." Harrison’s Principles of Internal Medicine confirms: "(AZT), used for treating (HIV), often causes severe megaloblastic anemia…caused by impaired DNA synthesis."

AZT reaches and can destroy foetal bone marrow too. In the May 1998 issue of the Pediatric Infectious Diseases Journal, Watson et al at the University of Rochester Medical Center in New York reported the grim case of an HIV-negative baby born to a positive mother who had been treated with a HAART cocktail of AZT, 3TC and a protease inhibitor, suffering "high output congestive heart failure secondary to profound anemia." The paediatricians excluded "infection, nutritional deficiencies, congenital leukemia and congenital red blood cell aplasia in the child" and considered the "cause of the life-threatening anemia in our infant…to be in utero erythroid marrow suppression by one or more of the antiretroviral agents administered to the mother."

Martin alleges that "toxicity in most cases is reversible." This optimistic jive is flatly contradicted by Mir and Costello, who reported their concern in The Lancet in 1988 that "bone marrow changes in patients on zidovudine seem not to be readily reversed when the drug is withdrawn. These findings have serious implications for the use of zidovudine in HIV positive but symptom-free individuals."

As for the fabled power Martin claims for AZT to prevent pregnant women transmitting HIV to their foetuses, Bennet observed in AIDS/STD Health Promotion Exchange 1998 that, "At present, data regarding the effects of ZDV (AZT) use on vertical transmission rates are inconclusive and incomplete. In addition, the long-term effects of ZDV use during pregnancy and after birth on the woman and any resulting child are yet to be discovered. The possibility has not yet been ruled out that this ‘risk-reducing’ measure may not be effective and may prove detrimental to the health of both mother and child."

Bennet’s caveat has moved from the hypothetical to the tragically real. In February, French researcher Stephane Blanche announced at the Sixth Conference on Retroviruses and Opportunistic Infections that two babies in an AZT trial that he and colleagues were conducting had apparently been killed by the drug. Both had fallen sick at four months and had died of mitochondrial dysfunction and neurological defects - conditions ordinarily very rare. In September, in his paper in The Lancet entitled Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues, he reported: "We analysed observations of a trial of tolerance of combined zidovudine and lamivudine and preliminary results of a continuing retrospective analysis of clinical and biological symptoms of mitochondrial dysfunction in children born to HIV-1-infected women in France.... Eight children had mitochondrial dysfunction. Five, of whom two died, presented with delayed neurological symptoms and three were symptom-free but had severe biological or neurological abnormalities. Four of these children had been exposed to combined zidovudine and lamivudine, and four to zidovudine alone. No child was infected with HIV-1... Our findings support the hypothesis of a link between mitochondrial dysfunction and the perinatal administration of prophylactic nucleoside analogues.….. Further assessment of the toxic effects of these drugs is required." On the same theme, in the same issue of The Lancet, Dutch researchers Brinkman et al published a paper recording their view that AZT class drugs "are much more toxic than we considered previously." Discussing the body-wasting characteristic of AZT-treated patients, they point out that, "The layer of fat-storing cells directly beneath the skin, which wastes away…is loaded with mitochondria… (O)ther common side effects of (AZT and like drugs are) nerve and muscle damage, pancreatitis and decreased production of blood cells… all resemble conditions caused by inherited mitochondrial diseases."

American researchers (Culnane et al), who in January had claimed in the Journal of the American Medical Association that AZT appeared to be safe for babies, were incredulous when Blanche made his conference announcement. Which is odd, because a month earlier a paper in AIDS by Lorenzi et al at Hopital Cantonal Universitaire in Geneva reported that, "Following combination antiretroviral therapy administered during pregnancy, most HIV-positive mothers and about half of their children developed one or more adverse events." Of thirty babies, "the most common adverse event was prematurity (ten infants), followed by anaemia (eight). The investigators also noted two cases of cutaneous angioma, two cases of cryptorchidism, and one case of transient hepatitis. Two infants…developed… intracerebral hemorrhage…(and one,)…extrahepatic biliary atresia."

None of this is really surprising since as early as 1990, Gillet et al had reported in the Journal of Gynecology, Obstetrics, and Biological Reproduction that "concentrations of (AZT) in the liquor and in the fetal blood (of six aborted human foetuses) were higher or equaled those found in the maternal blood." They reiterated accordingly, "The drug remains contra-indicated in pregnancy." Not least because the FDA categorises AZT as a 'C'-class drug for safety in pregnancy. With such drugs, it warns, "Safety in human pregnancy has not been determined, animal studies are either positive for fetal risk or have not been conducted, and the drug should not be used unless the potential benefit outweighs the potential risk to the fetus."

In a paper published in Mutation Research in 1997, Argawal and Olivero reported, "AZT induces significant toxic effects in humans exposed to therapeutic doses… Cytogenetic observations on H9-AZT cells showed an increase in chromosomal aberrations and nuclear fragmentation when compared with unexposed H9 cells (and) the mechanisms of AZT induced cytotoxicity in bone marrow of the patients chronically exposed to the drug in vivo may involve both chromosomal and mitochondrial DNA damage." This might explain Kumar et al’s 1994 report in the Journal of Acquired Immune Deficiency Syndrome and Human Retrovirology of a shocking number of therapeutic and spontaneous abortions, and, of the live births, a ten per cent abnormality rate among one hundred and four cases of pregnant women treated with AZT in a hospital in India. The grotesque birth defects included holes in the chest, abnormal indentations at the base of the spine, misplaced ears, mis-shapen faces, heart defects, extra digits and albinism. Doesn’t the doctor’s Hippocratic promise not to administer poison apply anymore?

The danger for developing foetuses posed by the administration of AZT to pregnant mothers was highlighted in 1997 by Ha et al in the Journal of Acquired Immune Deficiency Syndrome and Human Retrovirology in a paper entitled, Fetal, infant, and maternal toxicity of zidovudine (AZT) administered throughout pregnancy in Macaca nemestrina. The researchers reported, "The AZT animals (Macaque monkeys given AZT during pregnancy) developed an asymptomatic macrocytic anemia, but hematologic parameters returned to normal when AZT was discontinued. Total leukocyte count decreased during pregnancy and was further affected by AZT administration. AZT-exposed infants were mildly anemic at birth. AZT caused deficits in growth, rooting and snouting reflexes, and the ability to fixate and follow near stimuli visually." The latter indications of neurological damage were anticipated in their 1994 paper in the same journal, Fetal toxicity of zidovudine in Macaca nemestrina: preliminary observations. They found that, "AZT-exposed infants took three times as many sessions (6) as controls (2) to meet criterion on Black-White Learning, a simple discrimination task (and were)…significantly (worse in locating) the reward…" That's not all they found either: "Postnatal weight increase was significantly lower in AZT-exposed infants… Hemoglobin dropped significantly in the AZT-treated animals after treatment began and remained low until the end of the study... Platelet counts increased significantly in AZT-treated animals during the treatment period but returned to control levels before the end of the study... The mechanism for the elevation of platelet count in AZT-treated animals is unknown… The hematological toxicities reported here are consistent with those seen in 500 mg/day AZT-treated humans." Incredibly, Connor et al in their piece (discussed in my first essay) Reduction of Maternal-Infant Transmission of Human Immunodeficiency Virus Type 1 with Zidovudine Treatment, the pitiful if hugely popular paper in the New England Journal of Medicine in 1994 propounding the administration of AZT to pregnant women, rely on Ha et al's just-mentioned 1994 monkey research report for the comforting conclusion, "Based on these findings, we predict that there would be no significant toxic effects of prenatal AZT exposure (100 mg/dose; 500 mg/day) in humans." In the light of all that was already known about the acute toxicity of AZT, and it would be reinforced by later studies, what better illustration of Erasmus’ foresight in the 16^th century that the dullest, most ignorant and incautious doctors would become the superstars of the AIDS age, and that for their experiments on pregnant women with cell-poisons they’d be not abjured but celebrated. On trial, no doubt, they would defend their science in radical ideological terms like the doctors at Nuremberg. The evil they perceived called for ruthless measures to root out, and in such struggles conventional civilised restraints on medical experiments on humans fall by the way.

As an advocate of AZT for HIV-positive children, Martin might like to venture an explanation for this: In a study in the US, designed by Dr. Janet Englwood, and sponsored by both the National Institute of Allergies and Infectious Diseases and the National Institute of Child Health and Human Development, eight hundred and thirty nine HIV-positive children were divided into three groups and treated with AZT, ddI and a combination of both respectively. The ‘AZT alone’ wing of the study had to be abruptly called off in February 1995 due to the "more rapid rates of…bleeding and biochemical abnormalities" exhibited by the children in this group. For the answer, here’s a clue. In 1997, Benbrick et al reported a study by researchers at several French institutions in the Journal of Neurological Science; comparing AZT with other similar nucleoside analogue drugs used in AIDS treatment, they found that although "all (such drugs) exert cytotoxic effects on human muscle cells and induce functional alterations of mitochondria…AZT seemed to be the most potent inhibitor of cell proliferation."

Consonant with this finding, in 1997 in the journal Clinical Infectious Diseases, Heresi et al reported fungal infestations (PCP) which developed in the lungs of two HIV-negative babies, born healthy, whose mothers had been treated with AZT followed by the babies themselves for six weeks. No mystery about it. Under the entry ‘Retrovir’ (AZT’s trade name), The Physician’s Desk Reference hints delicately, "It was often difficult (in AZT clinical trials) to distinguish adverse events possibly associated with administration of Retrovir from underlying signs of HIV disease or intercurrent illnesses." In similar terms, the 16^th edition of the manual USP DI: Drug Information for the Health Care Professional published in 1996 by the United States Pharmacopeial Convention states that "it is often difficult to differentiate between the manifestations of HIV infection (again presumed) and the manifestations of zidovudine. In addition, very little placebo controlled data is available to assess this difference." To put a point on it, AZT itself can cause AIDS-defining illnesses. Its critics have been saying so for years. What else is one to make of Buchbinder et al’s finding reported in AIDS in 1994 that, "Only 38% of the HLP (healthy long-term (>10 years) positives) had ever used zidovudine or other nucleoside analogues, compared with 94% of the progressors"? Or Washington University's Assistant Professor of Medicine Dr Carl Fichtenbaum's observation about Mycobacterium avium complex disease in his article I Hear You Knockin' in the magazine Research Initiative Treatment Action: "Mycobacterium avium complex disease is one of the most common OI's in persons with advanced HIV disease. It has been observed in 15 to 40% of persons with HIV infection. The incidence of MAC began with AIDS reported to the CDC had MAC disease. Of note, the incidence increased from 5.7% in 1985-86 to 23.3% in 1989-90. Thus, MAC disease has become one of the most frequent OI events occurring in individuals with CD4+ lymphocyte counts <50 cells/mm3." Funny how the disease incidence suddenly ballooned coincidentally with the introduction of AZT as an AIDS drug in 1986-7.

In the June issue of the New England Journal of Medicine, Learmont et al report the interesting case of eight "transfusion recipients…infected with…HIV-1…from a single donor before 1985… Since then, two subjects died of causes unrelated to HIV-1 infection. The (cause of) death of one other subject, in 1987 (is indeterminate, and the five other) recipients are still asymptomatic 14 to 18 years after infection and have not received antiretroviral therapy." Wonder of wonders. Likewise, in the July issue of the Journal of Medical Virology, Candotti et al's study of sixty eight 'long term non-progressors mentions coincidentally that none were on "antiretroviral therapy". This tallies with the observation of prominent AIDS researcher Dr Jay Levy, Professor of Medicine at the University of California at San Francisco, in The Lancet last year that "long-term survivors of HIV" have all avoided 'antiretrovirals'. Similarly Dr Donald Abrams, Professor of Medicine and Director of the AIDS program at San Francisco General Hospital, noted in 1996: "I have a large population of people who have chosen not to take any antiretrovirals... I've been following them since the very beginning... They've watched all of their friends go on the antiviral bandwagon and die."

In 1997, The Canadian Pharmaceutical Association noted, "The long-term consequences of in-utero and infant exposure to zidovudine are unknown. The long-term effects of early or short-term use of zidovudine in pregnant women are also unknown." Likewise the US Centers for Disease Control’s April 1998 Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection cautioned, "Data from clinical trials that address the effectiveness of antiretroviral therapy in asymptomatic infants and children with normal immune function are not available… The theoretical problems with early therapy include the potential for short- and long-term adverse effects, particularly for drugs being administered to infants aged <6 months, for whom information on pharmacokinetics, drug dosing, and safety is limited…(and) clinical trial data documenting therapeutic benefit from (antiretroviral therapy) are not available."

However, in his paper in AIDS in May, Rapid disease progression in HIV-1 perinatally infected children born to mothers receiving zidovudine monotherapy during pregnancy, Professor de Martino, Coordinator of the Italian Register of HIV Infected Children at the Department of Paediatrics, University of Florence in Italy reports that, "Comparison of HIV-1-infected children whose mothers were treated with ZDV with children whose mothers were not treated showed that the former (AZT treated) group had a higher probability of developing severe disease [57.3%…versus 37.2%]…or severe immune suppression [53.9%…versus 37.5%…] and a lower survival (rate) [72.2%…versus 81.0%…]." How does this square up with Martin’s urging that AZT be given to pregnant women for the benefit of their children? In similar vein, in her jolly piece in the San Francisco Examiner on 31 May, Thailand wins a round against HIV, Karen Emmons reports, "Of the children who were born HIV-positive in Bangkok in the past four years and received the combination drug treatment (AZT and ddI)…one-fourth died in their first year, about 33 percent by their second year, 40 percent by age 3, and then the mortality tapered off." This is a medical victory? On these data, a critical journalist might have reported an iatrogenic drug disaster.

That’s just what some observers think AIDS in the US largely to have been, and if one looks at the CDC’s AIDS mortality figures read against the frequency of AZT use there, it’s not hard to see why. AIDS deaths trebled between 1988 and 1989 with the recommendation that AZT be given to asymptomatic HIV-positives; they rose steadily by 1994/5 to fifteen times what they had been prior to the introduction of AZT as an AIDS drug in 1986/7, and then fell precipitously - by 1997 to less than half of the 1994/5 death rate following the abandonment of AZT-monotherapy in favour of ‘combination therapy’, still toxic but not as immediately so. The peculiar part of it is that having been found to be too poisonous and ineffective as a monotherapy for adults by 1994, AZT should thereafter be commended for babies in utero.

One would think that all this would give pause to doctors plying this drug on pregnant women, but not in the debased scientific atmosphere of the AIDS era. One wonders whether the First Precept of the Nuremberg Code - informed consent - formulated after the Nazi medical experience, is ever observed with such dangerous experimental treatment. Any bets on whether these women are told, for instance, of Olivero et al’s report in 1997 in the Journal of Acquired Immune Deficiency Syndrome and Human Retrovirology bluntly headed, AZT is a Genotoxic Transplacental Carcinogen in Animal Models? The researchers reported that, "In newborn monkeys and mice, AZT was incorporated into DNA of many fetal tissues… AZT appears to be a moderately-strong transplacental carcinogen… (and in) adult mice, lifetime AZT administration induces vaginal tumors at a 10-20% incidence." Or of the same researchers’ other paper in 1997 in the Journal of the National Cancer Institute entitled Transplacental effects of 3’-azido-2’,3’-dideoxythymidine: tumorigenicity in mice and genotoxicity in mice and monkeys? In the light of earlier rodent studies which found AZT "to be carcinogenic in adult mice after lifetime oral administration", the research team, all scientists with the US National Cancer Institute, were concerned to assess "the transplacental tumorigenic and genotoxic effects of AZT in the offspring of…mice and…monkeys given AZT orally during pregnancy." Pregnant mice and monkeys were given AZT in the second halves of their gestational terms. After exposure to AZT in the womb, the offspring of these animals were not further treated. By one year of age, the mice exposed to AZT in utero "exhibited statistically significant, dose-dependent increases in tumor incidence and tumor multiplicity in the lungs, liver, and female reproductive organs. AZT incorporation into nuclear and mitochondrial DNA was detected in multiple organs of transplacentally exposed mice and monkeys. Shorter chromosomal telomeres were detected in liver and brain tissues from most AZT-exposed newborn mice but not in tissues from fetal monkeys." The researchers concluded, "AZT is genotoxic in fetal mice and monkeys and is a moderately strong transplacental carcinogen in mice examined at 1 year of age. Careful long-term follow-up of AZT-exposed children would seem to be appropriate." Since, "AZT is unequivocally a transplacental genotoxin and carcinogen (and) given transplacentally to mice, benzopyrene produced lung and liver tumour multiplicities similar to those observed (with AZT)", the researchers recorded their concern that "the current practice of treating HIV-positive women and their infants with high doses of AZT could increase cancer risk in the drug-exposed children when they reach young adulthood or middle age."

Nor does it seem very likely that HIV-positive pregnant women will be told of Olivero et al’s paper in AIDS in May, reporting the research of a major collaborative investigation by several institutions in the US, overseen by The National Cancer Institute: In view of the just-mentioned 1997 animal research findings, the researchers were concerned to establish whether their observations applied to humans, that is, whether AZT administered to HIV positive pregnant women was incorporated into their DNA and that of their babies. It was found that it was. The ramifications of this for the potential human carcinogenicity of AZT were conveyed in the researchers’ recommendation that "the biologic significance of ZDV-DNA damage and potential subsequent events, such as mutagenicity, should be further investigated in large cohorts of HIV-positive individuals (because)…these data raise the possibility that the presence of extensive ZDV incorporation into human DNA may be cumulative, with potential long-term consequences such as mutagenicity and tumorigenicity."

And it sure would be surprising were these women - advised to go on a bracing ‘short course’ of AZT treatment - to be told about Olivero’s paper in Mutation Research in July: 3’-azido-3’-deoxythymidine transplacental perfusion kinetics and DNA incorporation in normal human placentas in similar terms perfused with AZT: Olivero and Poirier of the Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, USA, and Parikka and Vahakangas of the Department of Pharmacology and Toxicology, University of Oulu, Finland. Concerned because "transplacental exposure studies demonstrated that AZT is a moderate to strong transplacental carcinogen in mice (and) the consequences of transplacental AZT exposure to the fetus remain unknown", the researchers investigated "the extent and kinetics of AZT transfer across the human placenta." They reported, "Since AZT crosses the human placenta and becomes rapidly incorporated (within 2 hours of AZT perfusion) into DNA of placental tissue in a dose-dependent fashion, (this suggests) that even short exposures to this drug might induce fetal genotoxicity… In previous studies AZT has been shown to produce both large-scale DNA damage and point mutations. Skin tumors induced in mice by transplacental AZT initiation and subsequent topical promotion had mutations in Ha-ras Exon I codons 12 and 13, but these mutations were not observed in liver and lung tumors from mice given the same exposure. The fact that the recommended treatment involves AZT use for the last 6 months of pregnancy, suggest that human fetuses may also sustain AZT-DNA damage… (T)he consequences of any fetal exposure to a nucleoside analog, in utero, remain unknown and a long-term follow up of children prenatally exposed seems to be appropriate."

Reporting to the US Surgeon General in 1970, the Ad Hoc Committee on the Evaluation of Low Levels of Environmental Chemical Carcinogens recommended, "Any substance which is shown conclusively to cause tumors in animals should be considered carcinogenic and therefore a potential cancer hazard for man… No level of exposure to a chemical carcinogen should be considered toxicologically insignificant for man. For carcinogenic agents a ‘safe level for man’ cannot be established by application of our present knowledge..." Have the rules changed? Is AZT too big to ban (under the Delaney Amendment outlawing potentially carcinogenic drugs in the US)? Or are the rules about exposing patients to likely carcinogens just relaxed a bit when they are female and pregnant? Or black or gay?

In fact the likely carcinogenicity of AZT, demonstrated by these recent studies, is no news at all. Way back in December 1986, a review of numerous AZT studies entitled Review & Evaluation of Pharmacology & Toxicology Data was submitted to the US Food and Drug Administration by its in-house toxicology analyst Dr Harvey Chernov. He reported - apart from the observation that AZT was toxic to bone marrow and caused anaemia in all species (of experimental animal) including man - that AZT "was found weakly mutagenic in vitro in the mouse lymphoma cell system. Dose-related chromosome damage was observed in an in vitro cytogenetic assay using human lymphocytes", and AZT was found to be active in the Cell Transformation Assay, a stock test for carcinogenic potential. He emphasized, "This BALB/c-3T3 neoplastic transformation assay was performed according to standard operating procedure. Concentrations of AZT as low as 0.1 mcg/ml reduced the number of cells in culture after a 3-day exposure. A statistically significant increase in the number of aberrant ‘foci’ was noted at concentration of 0.5 mcg/ml. This behaviour is characteristic of tumor cells and suggests that AZT may be a potential carcinogen. It appears to be at least as active as the positive control material, methylcholanthrene." As Chernov explains it, "A test chemical which induces a positive response in the Cell Transformation Assay is presumed to be a potential carcinogen." Naturally he advised the FDA against approving AZT, but his report was buried. Indeed, it had to be flushed out of the FDA’s files by resort to the machinery of the federal Freedom of Information Act, some years later.

Chernov’s bleak predictions have since been realised. But you’d never know it reading the tortured spin of AZT promoters Broder et al in their piece, Clinical Pharmacology of 3'-Dideoxythymidine and Related Dideoxynucleosides, published in the New England Journal of Medicine in 1989. Conceding that "it is of particular concern that the drug may be carcinogenic or mutagenic" and "its long term effects are unknown", the authors state, "zidovudine may be associated with a higher incidence of cancers in patients whose immunosurveillance mechanisms are disturbed simply because it increases their longevity." Just muse on that as a vignette illustrating the quality of reasoning exhibited by AIDS scientists, and then before you dry your eyes, dig this - from the same illustrious peer-reviewed journal: In 1988, Pizzo et al claimed that AZT boosted the IQ points of twenty one HIV-positive children by fifteen points. In declaiming these AZT-boosted "neurodevelopmental" improvements, the excited researchers relegated the deaths of five of the children on AZT to a passing mention. But not even that for the dead children when Glaxo-Wellcome seized on and punted this garbage as a selling hook when advertising AZT in The Lancet.

Actually, AZT doesn’t make you clever, it makes you stupid. You may have heard of ‘AIDS-dementia’. It’s like ‘neuro-syphilis’ - which no one gets anymore, now that penicillin has taken over from arsenic and mercury salts to kill syphilis spirochaetes. To be told by a doctor that you’re about to die would knock the best of us off the psychological rails. Certainly I’ve seen this in two AIDS-based cases I’m conducting. (At the least of it, the diagnosis per se can precipitate a health collapse, as a glance at Ader, Felten and Cohen’s text, Psychoneuroimmunology will confirm.) Bacellar et al reported in the journal Neurology in 1994 that "the risk of developing HIV dementia among those reporting any antiretroviral use (AZT, ddI, ddC, or d4T) was 97% higher than among those not using this antiretroviral therapy… In addition, the findings of our analysis seem to confirm previous observation of a neurotoxic effect of antiretroviral agents…linked…to the development of toxic sensory neuropathies, usually in a dose-response fashion." Remember the sensory and mental disturbances mentioned above on the package blurb as being among AZT’s ‘side-effects’? You know, the ones caused by the poisoning of your nerves and brain? Heald et al mentioned some of them in their paper in AIDS in 1998, Taste and smell complaints in HIV-infected patients. In a discussion of mitochondrial myopathy, Robbin’s Pathologic Basis of Disease mentions mitochondrial encephalomyopathy. The Concise Oxford Medical Dictionary tells us that encephalomyopathy is "extensive destruction of nerve cells throughout the nervous system (causing) widespread disease of brain and spinal cord."

In the May issue of Clinical Infectious Diseases, Fichtenbaum et al at the Washington University School of Medicine describe the cases of three patients who developed progressive multifocal leukoencephalopathy after four to eleven months of HAART. Despite a change in their treatment, the research team "observed no improvement (in two of the cases)… Neurologic deterioration continued, and (the) patients died within 2 months." They concluded that the condition can "develop while using HAART" notwithstanding test results suggesting "a good virologic response to antiretroviral therapy." That the drugs themselves caused the brain and neurological damage, they didn’t consider. Apparently Fichtenbaum and his portly pals found the logical leap too wide to hazard. But not Research Initiative Treatment Action in their piece headed Just Sweat it Out: Physical therapy’s role in the HIV pandemic under the chapter, The Nervous System and Physical Therapy: "Peripheral neuropathy pain, which occurs in 40 to 60% of people with AIDS, is one of the most common causes for referral to physical therapy and is often one of the most neglected. Symptoms of peripheral neuropathy include burning, numbness, and/or a tingling sensation of the extremities. Lower extremity involvement is more common than upper extremity involvement. Problems with ambulation, balance, and compensatory low back pain are also commonly associated with peripheral neuropathy." Since there isn’t a jot of evidence that HIV attacks nerve cells, but ample evidence that nucleoside analogues like AZT, 3TC, d4T, ddI and ddC do, the article concedes that "peripheral neuropathy may be directly related to (such) pharmacological agents…"

If it’s not good for your head, AZT’s not great for your heart either. Lipshultz pointed out in the New England Journal of Medicine in 1998 that "possible mechanisms (for heart muscle disease among HIV-positive patients) include cardiotoxicity as a result of antiretroviral therapy..." And in their paper in Nature Medicine in 1995, Mitochondrial toxicity of antiviral drugs, Lewis and Dalakas mention heart disease among the many manifestations of drug toxicity caused by ‘antiviral’ nucleoside analogues (ANAs) like AZT: "(T)he prevalent and at times serious ANA mitochondrial toxic side-effects are particularly broad ranging with respect to their tissue target and mechanisms of toxicity: Haematalogical; Myopathy; Cardiotoxicity; Hepatic toxicity; Peripheral neuropathy."

It would appear that AZT and chemically related drugs can blind you too. In the Journal of Infectious Diseases in March, Karavellas and Plumm reported their investigation of "the likelihood of the development of a new ocular inflammatory syndrome (immune recovery vitritis, IRV), which causes vision loss in AIDS patients with cytomegalovirus (CMV) retinitis, who respond to HAART. We followed 30 HAART-responders with CD4 cell counts of >/=3D60 cells/mm3. Patients were diagnosed with IRV if they developed symptomatic vitritis of >/=3D1+ severity associated with inactive CMV retinitis. Symptomatic IRV developed in 19 (63%) of 30 patients…over a median follow-up from HAART response of 13.5 months… These data suggest that IRV develops in a significant number of HAART-responders with CMV retinitis..." It's amazing. Some 'successfully' treated AIDS patients go blind. A brand-new disease construct comes into being: 'Immune Recovery Vitritis'. Roche hawks its 'anti-CMV medication', with advertising directed specifically at gay men whose sight has been wrecked by drug damage to their ocular nerves. In an echo of the Japanese Clioquinol disaster, cytomegalovirus is blamed for the blindness, not the HAART drugs, notwithstanding their well-established neuro-toxicity.

During a polio-like epidemic in the sixties and early seventies in Japan, Subacute Myelo-Optico-Neuropathy or S.M.O.N. caused blindness, paralysis and death in thousands of cases. The Japanese medical research establishment approached the crisis on the footing that some new unknown infectious agent was responsible. Echo-, Coxsackie- and lenti-viruses were put in the dock in turn. Professor Shigeyuki Inoue at Kyoto University's Institute for Virus Research claimed that a virus he had identified (coincidentally in the same herpes-class as the common-place and generally harmless cytomegalovirus) was the cause of S.M.O.N., and it was accepted as such in the 1974 edition of the American textbook, Review of Medical Microbiology. With modern medicine's bias to germs as the causes of disease, entirely overlooked was the possibility that the epidemic was caused not by a contagion but by a toxin - until the epidemiological anomalies became uncontainable for the viral culprit theory. Finally, an anti-diarrhoereal drug Clioquinol was found to be the cause. Inadequately tested, it turned out to be neuro-toxic. When it was banned, the plague ceased, and in the litigation that followed its manufacturer Ceiba-Geigy was taken to the cleaners.

But back to cancer. Pluda and colleagues, all researchers with the US National Cancer Institute, no less, reported in 1990 in Annals of Internal Medicine that on AZT, your chances of developing lymphoma relative to the rest of the population went up 50 fold: "The estimated probability of developing (Non-Hodgkin) lymphoma (in patients taking AZT alone, or in combination) by 30 months of therapy was 28.6% and by 36 months, 46.4%." The authors considered "a direct role of therapy itself" for the development of the disease, and warned, "Zidovudine can act as a mutagen."

In the light of these reports, is it truthful for AZT manufacturer Glaxo-Wellcome to persist with the assertion, as it does in its AZT package insert that, "It is not known how predictive the results of rodent carcinogenicity studies may be for humans"? After all, "At doses that produced tumors in mice and rats, the estimated drug exposure (for mice) …was (only about) 3 times…the estimated human exposure at the recommended therapeutic dose of 100 mg every 4 hours." And how frank is Glaxo-Wellcome in disposing of Chernov’s positive Cell Transformation Assay findings with the bald unelaborated statement in the same package insert, "In an in vitro mammalian cell transformation assay, zidovudine was positive at concentrations of 0.5 µg/ml and higher"? How many doctors, let alone patients, appreciate from this that as little as half a millionth of a gram per millilitre of AZT came up positive in a standard drug-industry screening-test for potential drug carcinogenicity? And what risks for patients this portends?

In AIDS in May, Grulich et al report a 16 year study of cancer incidence among people given an AIDS diagnosis in New South Wales, Australia. The researchers noted that among more than 3600 AIDS diagnoses, fully one quarter of the patients had developed cancers including those of lung, skin and lip, leukaemia and Hodgkins Disease - none of which are ‘AIDS indicator diseases’. "There was an increased incidence of several other forms of cancer, some of which are known to occur at increased rates in transplant recipients who have received immunosuppressive therapy." Presumably these patients had been dosed according to the standard ‘antiretroviral’ treatment protocol - AZT alone or in combination with related drugs. All of which, like ‘immunosuppressive therapy’, are destructive of the cells of the immune system. They report, "The incidence of Hodgkin’s Disease increased significantly at the time of AIDS diagnosis." Since the disease sets in after the diagnosis is made and the treatment begins, the sensible doctor might wonder about the medicine. Such enquiry might be stimulated by Zietz et al's paper in June in the New England Journal of Medicine reporting An unusual cluster of cases of Castleman's disease during highly active antiretroviral therapy for AIDS. Most patients with this "rare… lymphatic hyperplasia…disease" typically present with "multicentric lymphadenopathy… an interfollicular predominance of plasma cells… and progressive systemic symptoms or with a more localized, indolent disease that can often be cured by local excision." In the four cases reported, the patients suffered "(f)ever, weakness, generalized enlargement of lymph nodes, and marked polyclonal gammopathy… (and three) died within a week after the diagnosis." Speculating about the possible causes - the virus HHV-8 is tentatively mooted - the authors note that in all cases "symptoms of multicentric Castleman's disease started after the initiation of highly active antiretroviral therapy…" Sure they did.

Debunking Martin’s claims as to the efficacy of AZT for "post-exposure prophylaxis" would take more space than the joke warrants. Put it this way. There are no smart-bomb drugs for viruses. Probably never will be. If there were, we wouldn’t have to put up with colds and ‘flu any more. Geddit?! As Nobel Laureate retrovirologist and Director of the US National Institutes of Health, Dr. Harold Varmus summed it up in June last year, "Trying to rid the body of a virus whose genome is incorporated into the host genome may be impossible." Any honest, competent GP will tell you that viruses are beyond Medicine’s reach. With viral diseases you take it easy and hope for the best. Presuming of course you have the disease you’ve been told you do, but just what HIV antibody test results really tell is another story, and what an unbelievable scientific shambles it is.

Schmitz et al’s paper Side effects of AZT prophylaxis after occupational exposure to HIV-infected blood in Annals of Hematology in 1994 might dampen the ardour of AZT ‘post exposure prophylaxis’ proponents: AZT was supplied to fourteen health care workers "exposed to HIV contaminated blood through needle sticks and similar accidents." Three abandoned the treatment early because of its unendurable toxicity. Eleven held the course for a month. Four of them developed severe neutropenia. One developed a lung infection. The study itself was called off early before more harm was done. Robbins’ pathology text explains: "The symptoms and signs of neutropenias are those of bacterial infections (and) the most severe forms of neutropenias are produced by drugs." Hello?

Following the rape recently of prominent South African AIDS journalist Charlene Smith, an intense debate currently rages in the media here about a related issue: whether the State ought to provide AZT and related drugs to rape victims. However the US Centers for Disease Control, the font et origo of most conventional wisdom about AIDS, is not on the side of its protagonists. In CDC Update, dated 29 Sept 1998, it warned, "Potential benefits must be weighed against the risks of drug toxicity (and) the difficulty of compliance with the regimen… Because post-exposure is an experimental therapy of unproven efficacy, it should only be prescribed with the informed consent of the patient, after explanation of the potential benefits and risks. Antiretroviral therapy should never be used routinely…" This advice was based on the conclusions of a conference of experts convened to examine the matter on 24-25 July 1997 in Atlanta. The report of this External Consultants’ Meeting on Antiretroviral Therapy for Potential Nonoccupational Exposures to HIV recorded that "no data currently exist about the effectiveness of such therapy for these types of exposures... There are no human studies of antiretroviral drug therapy for sexual, drug use, or other non-occupational exposures to HIV... Potential benefits have to be weighed against the significant health risks and costs associated with this therapy for nonoccupational exposures. First, these medications can have severe side effects… Second, efficacy is unknown... This therapy should never be routine. It is… complicated…(and) is NOT a ‘morning-after pill’."

Charlene Smith recently reported Amy Brown's experience of 'antiretroviral therapy'  in the Mail and Guardian (15 October). Five months after being raped she came up positive to an HIV antibody test. "I was eleven weeks pregnant and the doctor said Retrovir (AZT) and 3TC are not approved for pregnancy but you have to take it. I lost the baby a week later." Any wonder?

Finally, for AZT, a ringing epitaph. In June, in a special supplement to the journal Current Medical Research and Opinion, Papadopulos-Eleopulos et al publish an extensive critical analysis of the pharmacology of AZT*. It’s a monumental document (30 000 words) and it explodes all pretensions that AZT has ever had to having any therapeutic value. Reviewing all the principal medical literature on AZT, both early and current, the authors demonstrate that there is "no…evidence" to support early claims that AZT disrupts the "HIV replication cycle by a selective inhibition of viral reverse transcriptase thereby preventing the formation of new pro-viral DNA in permissive, uninfected cells", that AZT is not triphosphorylated to any significant extent in vivo when administered to patients - a process all HIV experts agree is essential to prevent the formation of pro-viral HIV DNA - and that AZT is incapable of exerting an anti-HIV effect accordingly. On the other hand, the paper mentions "a number of bio-chemical mechanisms (elucidated in the scientific literature) which predicate the likelihood of widespread, serious toxicity for the use of this drug." The authors wonder, "Based on all these data it is difficult if not impossible to explain why AZT was introduced and still remains the most widely recommended and used anti-HIV drug." They conclude that the continued administration of AZT "either alone or in combination…to HIV sero-positive or AIDS patients warrants urgent revision." This indictment of AZT ought to be its death knell in clinical practice. No doctor whose adult or infant patient sickens or dies on AZT will be safe from damages actions founded on medical negligence after this.

It took four centuries before Medicine finally recognised that Calomel (mercurous chloride) couldn’t cure, only kill, and dumped it from its pharmacopoeia. Until then, notwithstanding its manifest poisonousness, doctors had advocated it, some with poetic fervour, as a panacea for gout, headache, menstrual pain, syphilis, and no end of other ailments. No modern doctor, especially any who has seen that ghastly clip of Japanese families crippled by mercury poisoning in Minamata Bay in the fifties, or our own recent victims - former workers at the Thor mercury-waste ‘reprocessing’ plant in KwaZulu-Natal - would dream of ladling mercury salts down their patients’ throats nowadays. When is the penny going to drop with AZT?

The repackaging of lethal cell-poisons like AZT as ‘anti-retrovirals’ is a vast and vicious pharmaceutical fraud. But as a Greek Cynic noted appositely a couple of millennia ago, the law has always been a web in which small flies get caught; the great ones burst through.

So much for Doc Martin’s Celestial Elixir.