CHAPTER 7

Before we proceed to the matter of MTCT and nevirapine, let us briefly discuss the issue of AZT, which continues to have its own fans in our country. It is used by the provincial government of the Western Cape among African women allegedly for MTCT. Despite the unequivocal advice of its manufacturer that it should not be used in instances of rape, those intent on marketing this drug continue to demand that it should be made available for this purpose within our public health system.

In her book "Positively False", (I.B. Tauris, London: New York, 1998), Joan Shenton has written:

"In spite of the manufacturers claiming that (AZT) prolonged life and delayed the onset of AIDS, doctors actually working with patients could only see them getting sicker and sicker before their very eyes and then dying.

"Why? Quite simply, AZT is a DNA chain terminator. That means it destroys the mechanism by which new cells are made in the body. It stops the growth of DNA causing the fast or slow death of the immune system because all growing cells will be killed by the incorporation of AZT. Its action is similar to cancer chemotherapy, whereby bad cells are killed in the hope of keeping enough good cells to survive. In cancer chemotherapy the treatment is given for a limited period of time. AZT is prescribed indefinitely - until death. (Our emphasis).

"Other supporting evidence supporting irreversible damage from AZT had been published in The Lancet in 1988. Drs Christine Costello and Naheed Mir reported serious bone marrow damage in their patients on AZT, with 36 per cent requiring blood transfusions. The authors write, 'It is worrying that bone marrow changes in patients on zidovudine (AZT) seem not to be really reversed when the drug is withdrawn.(The Lancet, 19 November, 1988).

"Apart from inhibiting DNA synthesis and killing healthy cells, AZT (according to <the manufacturer> Wellcome's own official literature) has other serious effects on the body."

It is not accidental that AZT action is "similar to cancer chemotherapy", as Joan Shenton puts it. This is because it was developed in 1964 by a Dr Jerome Horwitz as a cancer chemotherapy drug. However it was abandoned even before it reached the stage of human trials because of its high levels of toxicity and its ineffectiveness against cancer.

The manufacturers of AZT, the then Glaxo Wellcome, presented it 20 years later as an anti-HIV drug. This was at a time when the scare mongering referred to earlier had produced great panic in the US that millions were going to die as a result of HIV/AIDS, the same panic that is now been sown among our people. Overnight, the abandoned cancer "treatment" AZT, became the miracle drug that would contain HIV/AIDS!

So great was the fear generated by the scare mongers that even the approved trial was abandoned before it was concluded.

In his book "Poison by Prescription: The AZT Story", (Asklepios 1990), John Laurintzen writes that 'Martin Delaney of Project Inform gives a fair summary of what emerges from the FDA material:

"The multi-center clinical trials of AZT are perhaps the sloppiest and most poorly controlled trials ever to serve as the basis for an FDA drug licensing approval. Conclusions of efficacy were based on an endpoint (mortality) not initially planned or formally followed in the study after the drug failed to demonstrate efficacy on all the originally intended endpoints. Because mortality was not an intended endpoint, causes of death were never verified. Despite this, and a frightening record of toxicity, the FDA approved AZT in record time, granting a treatment IND in less than five days and full pharmaceutical licensing in less than 6 months."

(NB: the FDA is the US Government's Food and Drug Administration which licences drugs and medicines. The FDA material used by Laurintzen and Delaney was obtained from the FDA under the Freedom of Information Act.)

Laurintzen reports that a conference on AIDS was held at Columbia University, New York, on 19 November, 1988. Dr Sonnabend was one of the speakers. Lairintzen says:

"Sonnabend began by saying that the toxicities of AZT should not lightly be dismissed. The harmful effects of the drug are real, and they are serious. Technically, AZT is a poison; it is cytotoxic (i.e. it kills cells). The drug cannot distinguish between infected and healthy cells; it kills both. Never before has a drug as toxic as AZT been prescribed for long-term use. The long-term effects of AZT, the cumulative toxicities are unknown. Sonnabend emphasised the ethical responsibilities of the physician, to be sure that there was a sound scientific basis for the benefits of the drug, considering that its toxicities were firmly established." (Our emphasis).

Ellen C. Cooper, M.D., M.P.H., was one of the FDA medical officers attached to the AZT trial. In her "Medical Officer Review of NDA 19-655" and "Addendum #1", she wrote that:

"(Several measures of viral activity were used,) and 'no statistically significant changes in the percent of positive cultures or time to detection of virus in culture were observed.

"Of particular concern is the possibility that the hematologic toxicity of the drug when administered over a prolonged period of time may eventually debilitate patients to such an extent that they may become less able to resist opportunistic infections and other complications of HIV-disease (sic) than if they had been left untreated.

"The majority of patients who were randomised to receive AZT in this trial experienced significant toxicity."

In his "Review & Evaluation of Pharmacology & Toxicity Data (of AZT)", Harvey I. Chernov, Ph.D., wrote:

"AZT may be a potential carcinogen. It appear to be at least as active as the positive control material, methylcholanthrene, (a known and extremely potent carcinogen).

"Thus, although the dose varied, anemia was noted in all species (including man) in which the drug has been tested.

"In conclusion, the full preclinical toxicological profile is far from complete with 6-month data available, but not yet submitted, one year studies to begin shortly etc. The available data are insufficient to support NDA approval."

"Current Medical Research and Opinion", Vol 15: Supplement, 1999, carries the following comment:

"At present, evidence also exists which shows that AZT is rapidly reduced by compounds containing sulphydryl (-SH); that is, AZT oxidises the -SH groups. Ample evidence also exists which shows that oxidation in general (and of -SH in particular) and decreased levels of ATP may lead to many laboratory and clinical abnormalities, including wasting, muscular atrophy, anaemia, damage to the liver and kidney, decreased cellular proliferation, cancer and immunodeficiency. Since patients who are at risk of AIDS are exposed to many oxidising agents and are known to have low -SH levels, one would expect AZT to have particularly toxic effects in these individuals - and the sicker the patient the more toxic the drug. That this is the case was accepted by researchers from the National Cancer Institute, Wellcome Laboratories and Abbott Laboratories as far back as 1988: 'Azidothymidine (AZT), however, is associated with toxicities than can limit its use.These toxicities are particularly troublesome in patients with established AIDS; the use of azidothymidine is often limited in this population."

Despite all the foregoing concerning the toxicity of AZT and the strange circumstances surrounding its licensing in the US, there are some in our country who are desperately keen that we make AZT generally available in the public health system, as we would ordinary headache tablets. Boldly, they claim to be the best friends of the African!

At least two questions arise from the foregoing:

· on what scientific basis did our Medicines Control Council (MCC) license AZT in our country?; and,

· should those doctors who prescribe AZT and other anti-retroviral drugs not be held personally liable in the event that their patients develop the illnesses caused by the toxicity of these drugs?