AZT Cause For Concern

Meditel 1992

Tonight, Dispatches challenges the claims made for the main anti-AIDS drug, AZT. In America later this evening, the results of a new study of life expectancy for those on the drug will be published. Those results will throw new doubts on the effectiveness of AZT. Tonight's Dispatch is the third on the subject of AIDS. As before, the programme's advice is clear; no-one should alter medication without consulting a doctor - still less, on the basis of a television programme. But the role of tonight's Dispatch is to examine the evidence. It will argue that in this country, the Wellcome Foundation, the manufacturers, are making false and misleading claims about the drug and could be in breach of the law. That's AZT - CAUSE FOR CONCERN.

In May, 1990, the American AIDS activist group ACT UP organised a demonstration outside the National Institutes of Health in Maryland. They were protesting about AZT or zidovudine, the only approved drug for AIDS. This was a remarkable about turn because three years earlier other ACT UP demonstrations had clamoured for more AZT to made available at a cheaper price. What had changes?

For several years the rock magazine Spin has run an AIDS column. In it journalist Celia Farber has kept a close and critical watch on AZT.

CELIA FARBER: "Attitudes about AZT have changed dramatically over the last couple of years and especially in the last year. The leaders of the gay community in the major cities here were on AZT, many of them in the beginning. And then when it stopped working for them they turned around and they said "It isn't working". Whereas initially they had defended it so adamantly."

GENE FEDORKO: "A lot of people who were involved with ACT UP, and who were on nucleoside analogues like AZT, had bad experiences with the drug eventually. And then there was a panic, and then there was this realisation, this horrible disillusionment that indeed the drug they were begging the government to get into their bodies were in fact very ineffective if not toxic."

If they were aware that the drug had unfortunate side effects, why were people so anxious to take it?

CHRIS BABICK: "Because there didn't seem to be any alternative. The propaganda was that AIDS is a hundred percent fatal which it isn't. There is a 15% survival rate today, and of course people are living longer, and people were desperate at that time, and didn't know much. AIDS is basically political. It's been politicised, moralised in this country and there's a lot of misinformation about the disease."

Through public protests and demonstrations AIDS activists were giving voice to serious misgivings about toxicity and the expectations for AZT amongst leading doctors and scientists.

DR. MICHAEL LANGE (Head of AIDS Programme St. Lukes Hospital, New York): "I think the central fact is that despite five years of AZT and trials, and four on the open market, people keep dying in large numbers, and hence it is clearly not as wonderful a drug or life saver as it is made out."

DR. JOHN HAMILTON (co-chair Veteran's Administration AZT Study, Durham, North Carolina): "First of all I think it's self evident that our study does not provide the kind of benefit that everyone wished for. It can't be a secret that patients wanted something that would help them live longer. Unfortunately it has not demonstrated that and therefore this has to be unwelcome news."

DR. ROBERT HOFFMAN (Professor Cancer Biology, University of California, San Diego): "Well the effect of AZT on body cells as a whole is very deleterious because it prevents cells from replicating. There's a second point in that cells that may survive AZT may themselves become cancerous so there is a double danger for AZT the way I see it."

When AZT was licensed in the United States in 1987 hopes were running high. Tucked away in a corner of the massive Jackson Memorial Hospital complex, is Miami University's AIDS research unit. Here Dr. Margaret Fischl was one of the leading figures in the trials that led to the licensing of the drug.

DR. MARGARET FISCHL: "I think in the very beginning when the studies were actually being designed, our greatest expectation or hope would be that it would delay progression of the disease, it would improve quality of life, decrease the severity of the disease. Although we designed survival benefits into this study we actually did not expect to see them."

At San Francisco General, Dr. Paul Volberding another leading AZT researcher supports AZT's early track record.

DR. PAUL VOLBERDING: "The drug was approved in 1987, for use in what we would now call advanced HIV disease, patients who had substantial deterioration, on the basis of a clinical trial that was really quite short. But a trial that showed, compared to the placebo, a rather striking difference in the mortality rate in patients with AIDS. So we stared experience with the sense that this was a very active drug clinically, but with still questions to be answered about the appropriate use of the drug, the appropriate dose of the drug."

The results of the early AZT trial on people with full blown AIDS appeared to be so convincing that the drug was given a new fast track approval by the United States Food and Drug Administration - before any long term toxicity trials in animals had been completed.

COMMISSIONER FRANK YOUNG: "These new regulations specifically will have special criteria that would apply to immediately life threatening conditions recognising that such patients are willing to accept the greater risk than that which normally would be the case."

The Wellcome Foundation, UK manufacturer of AZT saw its shares spiral upwards. AZT was to be the new wonder drug. Then in 1989 after further trials were terminated early in the United States because results looked promising, it was announced that AZT could be used not only in people with AIDS diseases but in a much larger group with HIV and low immune cell count but no other symptoms. Wellcome's shares soared to new heights adding 1.4 billion pound to the company's UK stock market value in one day. Today annual sales of AZT are worth around 170 million pound.

Opening up the drug's use to so-called "asymptomatics" means a substantial increase in the number of people who could be prescribed AZT indefinitely. In the UK the estimated number of HIV positive people is 50,000. In the United States it's around one million. This 1990 US poster campaign - Living with HIV - was co-sponsored by Burroughs Wellcome. People were encouraged to get tested for HIV. The posters said: 'Early medical intervention could put time on your side.' As AZT was the only approved drug for AIDS at the time this was a way of increasing Wellcome's market for the drug.

DR. MICHAEL LANGE: "I think it's a disgrace. It lures people into the belief that if they're HIV positive they should go and get themselves tested and that there's an answer that will keep them alive and that's far from the truth."

More and more people with no symptoms of AIDS but who have HIV and a low immune cell or T-cell count are being drawn into AZT studies. The Concorde trial based here at the Middlesex Hospital and at the Brompton Hospital in London involves some 3,000 British and French participants with HIV but no AIDS symptoms. In October last year, a progress meeting was held at the Terrence Higgins Trust. We were barred but an amateur recording has been handed to us. Professor Ian Weller, chairman of the Concorde trial working party, argued the case for continuing the trial.

DR. IAN WELLER: "It seems to me that the Data and Safety Monitoring Committee feel very comfortable in allowing this study to proceed into what I think is new territory. And my feeling is that it's that territory that most patients and physicians are interested in. that is if there is benefit, is it maintained, or will it wear off? In which case we may cause more harm than good."

Professor Weller said that the monitoring committee found no clear evidence on which to base new recommendations for clinical practice and that the trial into AZT or zidovudine would continue for a further seven months. He also said:

DR. IAN WELLER: "My feeling is that this is the only chance, that anyone will have of sorting out the uncertainty that I think is at the basis of some of the frustration. That is whether it is better in the mid to long term - rather than short term - to give zidovudine early or rather leave it to a later stage of infection. Early intervention does make biological sense. The question, the pragmatic question, the practical question is, do we have the right tool?"

AZT was first developed in 1964 as a cancer chemotherapy drug. It was designed to destroy proliferating cells. Later at the US National Cancer Institute in Maryland it was tested as an AIDS drug. Normally cancer chemotherapy drugs are used for limited periods but AZT is given for open ended use. It's effect on the body can be very serious. Some people simply can't tolerate it and suffer vomiting, muscle pain and unendurable headaches. Lower doses produce less side effects but on high doses bone marrow cells are affected with up to 30% of recipients needing blood transfusions.

DR. ROBERT HOFFMAN: "I believe that the drug AZT can have at least two important areas of toxicity and that is the inhibition of production of critical white cells and also the production of malignant cells such as lymphoma cells. The two courses can be monitored but they can also reach the point of no return where nothing can be done about it. So even with monitoring, these toxicities can be life threatening."

Although the effects of AZT also called by its generic name zidovudine are listed in Wellcome's US and UK information sheets for doctors, their promotional leaflet for doctors and the public in the UK makes some startling claims about AZT's safety and efficacy. For example, it states here that doctors can manage the serious blood problems and 'there are no life threatening toxicities associated with zidovudine.' These and other claims have encouraged some doctors and patients to embark upon high dose therapies, sometimes over long periods of time. There is evidence that some of these claims are false and others seriously misleading. There are worrying differences and omissions between the US and UK doctor's information sheets.

Before a drug is licensed for use it normally has to undergo animal toxicity studies and clinical trials in humans. No long-term animal studies were completed when AZT was licensed. The clinical studies in humans - called phase-II - which led to the licensing of AZT were financed by Wellcome. They were presented as complying with the only reliable scientific test for a drug - double blind studies - and published in the New England Journal of Medicine in July 1987. In this type of trial one group is given the drug and the other a placebo or a dummy tablet. Neither the volunteers nor their doctors should know who is getting what, in order to eliminate any bias in expectation of what a particular treatment, or no treatment, may do. This is called blinding. In this document Wellcome claims that: 'Non of the volunteers or the clinicians involved knew who had received placebo and who had received the active drug.'

We have the following evidence that the trials became unblinded early on. This internal document from the Food and Drug Administration, the US authority that licensed the drug, was obtained through the freedom of information procedure. Dr. Ellen Cooper in reviewing the AZT data writes: 'The fact that the treatment groups unblinded themselves early could have resulted in bias in the work up of patients.' If the FDA knew this then Wellcome would have been incompetent not to know.

Through the pages of the New York Native, a gay weekly newspaper, journalist John Lauritsen, author of the book AZT; Poison by Prescription, and deputy editor Neenya Ostrum have kept up constant pressure about inconsistencies in the events that led up to the licensing of AZT.

JOHN LAURITSEN: "There were so many contradictions. But the real horror of this study only became apparent after going through documents which were obtained under the Freedom of Information Act. And it indicated that there had been not only sloppiness of every conceivable sort but that there had been actual cheating in a number of areas. It indicated that the study had become unblinded very quickly in the first few weeks although it was planned as a double-blind placebo-controlled study. In fact, it was nothing of the kind. Both patients and doctors knew who was getting AZT and who was getting placebo."

As far as we can ascertain everyone in the phase-II trial has died. Chris Babick of People with AIDS Coalition used to advise trial participants on a telephone helpline where they could get their pills analysed.

CHRIS BABICK: "During the phase-II trials we received many phone calls in our office from individuals who wanted to determine whether or not they were using the placebo or actually receiving AZT. There were three laboratories in New York which would analyse the medication. We would refer individuals there. If in fact they were on placebo they would make arrangements to acquire the drug AZT. Often times they would share it with individuals who were in the trials and thus really rendering the phase-II trial, unblinding the phase-II trial."

Dr. Michael Lange helped run one of the trial centres.

DR. MICHAEL LANGE: "I don't think they were really blinded because when you take AZT your red blood cells increase in size and this happens after two to three weeks and you can notice that on an ordinary blood count, and since blood counts were monitored and the information fed back to patients, this information was available to the investigators."

DR. PAUL VOLBERDING: "Well, I don't think it's completely true that the trial was unblinded. There - in retrospect - are ways that we could have known who was taking the drug. The drug causes the red blood cells - for example - to enlarge in size. But that wasn't really known at the time. And so I think that trial was in fact quite well blinded."

Did you knew that the phase-II trials became unblinded earlier on in the study?

DR. MARGARET FISCHL: "Oh, I don't think it became unblinded. I think that's fanfare and does incredible misjustice to that trial. Did we know that, or suspect that some of the patients were on AZT? Of course. You know when you say unblinding you assume that the whole study is unblinded. That both the patients and physicians know exactly what they're on and that typically does not happen in most clinical trials. Are patients suspicious sometimes of what they're on? Yes. Do they necessarily change their behaviour because of that? No. do physicians or nurses that care for patients in blinded studies sometimes suspect what the patient is on? Yes. Does that necessarily change their behaviour in the conduct of a trial? No. they typically will proceed with the conduct of the trial as it is outlined."

JOHN LAURITSEN: "Well one could argue over how much of an effect it would have for a study to become unblinded. Certainly all kinds of biases are possible. It could be everything from the psychological effect on the patient to the way that the doctor managed it. But certainly the gold standard of drug testing is a double-blind placebo-controlled study. And most importantly, if the study was not blinded it is dishonest to describe it as being a blind study. And to this very day the advocates of AZT continue to say that this was a double-blind study when it was certainly nothing of the sort."

We would like to have put some questions to the Burroughs Wellcome Company based here in Raleigh North Carolina. Wellcome financed the phase-II trials that led to the fast track approval of AZT. They declined our invitation to be interviewed.

In the same UK promotional leaflet Wellcome claims that AZT is an antiviral drug. The leaflet gives the impression that AZT can target the HIV virus without killing cells. Professor of Molecular Biology at Berkeley, California, Peter Duesberg, is known for his view that HIV is not the cause of AIDS. His concern about the use of AZT stems not simply from this view but from a criticism of AZT's molecular activity. He objects to Wellcome claim that AZT is an antiviral drug.

DR. PETER DUESBERG: "That's is a euphemism. It's not wrong, but it kills or inhibits all DNA synthesis, everything that's going. It inhibits the cell first, and with it the virus."

Peter Duesberg and some other leading scientists claim that HIV has never been shown in humans to present a meaningful target for AZT. In order to understand these assertions we need to examine the way in which a retrovirus - like HIV - works.

The blueprint for all living cells is the double stranded DNA - deoxyribonucleic acid. But a retrovirus id different, it's made of a single stranded RNA - ribonucleic acid - which in order to replicate needs to insert itself into a cell's nuclear DNA. So, a retrovirus - like HIV - doesn't destroy it host cell. It penetrates the cell wall and with the help of an enzyme called reverse transcriptase converts its own single strand of RNA into a double strand of DNA. It can then insert itself into the nucleus of the cell. The fundamental life-giving process of cell re-generation depends on DNA. Which is made up of four building blocks which slot together. One of these is called thymidine. AZT is a copy or analogue of thymidine, which, when it attaches itself to the viral DNA chain, stops it because nothing else can attach itself. Some scientists claim that, whether a cell is infected with HIV or not, AZT terminates the DNA chain stopping more DNA from being formed.

DR. ROBERT HOFFMAN: "It inhibits the replication or duplication of DNA and thereby prevents the cell itself from duplicating."

Wellcome claims that AZT can target HIV and delay symptoms of AIDS in people who are HIV positive by inhibiting HIV when reverse transcription takes place.

DR. MARGARET FISCHL: "Once it enters that cell the drug has to undergo a transformation so it becomes active and then it actually prevents the virus from getting into the genetic make up of the cell and infecting that cell."

But Duesberg maintains that AZT can't prevent the virus from infecting that cell without killing it and others as well.

DR. PETER DUESBERG: "In people who are given AZT, healthy or sick, only one in five hundred cells is ever infected by HIV. That is to say in order to kill that one infected cell, we have to kill five hundred normal cells, god cells that people with AIDS desperately need to survive, and healthy people need them too. It is like trying to kill a terrorist in a city of Berkeley of 200,000 by poisoning the water. You may get the terrorist, but you will get most of the other people as well."

But does AZT have a viral target at all?

Peter Duesberg maintains that once a person has developed antibodies to HIV, HIV becomes inactive and there's essentially no more reverse transcription going on for AZT to target.

DR. PETER DUESBERG: "There's no evidence for it. It's not detectable, and the numbers of infected cells remain the same. It remains very low, and remains constant, which is direct proof that further infection is not taking place. Further infection depends on reverse transcription."

Dr. Harvey Bialy supports this view. He is research editor of Bio/Technology, sister to the science journal Nature. In this interview he is expressing his personal views.

DR. HARVEY BIALY: "The majority of time the person is infected with HIV there is essentially no reverse transcriptase activity that can be detected. So, it is really beyond me how a drug that is claimed to inhibit reverse transcription of the virus, inhibit virus replication, can be a suitable agent for treating AIDS, or even for that matter for treating HIV infection since the immune system does a very good job of keeping a virus replication at undetectable levels."

On the west and east coasts of the United Sates, the agony of AZT combined with the uncertainties about AZT, have led to the growth of support groups like HEAL, run by Michael Ellner, whose members seek alternative approaches to the treatment of AIDS. HEAL helps people who are suffering side effects come off AZT.

GENE FEDORKO: "They're scared. They know that they don't like the way that they feel and we show them other people who come to HEAL and there's always a good 20 to 30 people who are on cold turkey from AZT. They just stopped taking it."

Cliff Goodman has been HIV positive for four years. We asked him if he would take AZT.

CLIFF GOODMAN: "No way. I wouldn't give it to my cats. I would think it was murder. I've seen people go on AZT and I've seen them waste and their hair fall out, and their muscles shrivel below their knee. And I've seen many males become impotent. So, there's no way I'm gonna take something like that, you know. I think it's almost like a punishment."

ALLAN ROUNDTREE: "At first I gained weight and I said 'Boy, this stuff must be working.' And then about another two weeks later it did start working. The headaches came. The dizziness, the nauseousness and the whole time. And I had fingernails that were so black it looked like I had nail polish on, you know. And an upset stomach, nothing tastes right, food or anything. And the main thing, it would affect you so where you couldn't listen to people cause you don't wanna hear them because you're hurting so bad. And it left me impotent. It destroyed my hopes for living, you know."

Wellcome's AZT promotional leaflet in the UK states: 'Zidovudine... improves both the quality and length of life.'

We asked Dr. Lange if there is any data to support AZT prolonging life?

DR. MICHAEL LANGE: "I don't think that we have, that the data has been made available. The major problem is that all published AZT studies were prematurely concluded. And what happened to these people after the study was concluded is not very well known, nor is it published anywhere."

Do you believe that AZT prolongs life?

DR. MARGARET FISCHL: "In patients that have advanced disease? Yes. That has been shown in numerous studies. When used early, when patients are still asymptomatic, have no symptoms or they have minimal symptoms and their immune system is not severely damaged? There we know that AZT prevents or delays the occurrence of AIDS, which we felt in the United States was the most important thing to look for."

JOHN LAURITSEN: "The claim is made that AZT extends life - and yet most of the belief that it does - are based on the phase-II trials which - as I just said - were seriously flawed, utterly worthless. Other studies used to claim benefits for AZT range all the way from tiny little studies of uncontrolled patients. You know five or six here or there, which are really nothing better than anecdotes."

Dr. John Hamilton, at the Veteran's Administration Medical Centre in North Carolina, is co-chair of one of the longest completed AZT studies published in a leading American medical journal this week. The drug was given to 338 patients. One group early in the disease, and another when their immune cell count fell below 200. He believes that AZT should be given to people in the later stages of the disease, but is less certain about giving AZT to people early in the disease.

DR. JOHN HAMILTON: "The results of the trial demonstrated that patients on early therapy had a delay in the progression to AIDS. However, there was no difference in survival, comparing one group with the other. That is, the same number of individuals died in each group and the time at which they died was the same."

Individual people differ greatly in the way they react to drugs, and there's no way of knowing who will suffer severe side effects or tolerate the drug well. Jim Pruitt lives in Miami. He suffered AIDS symptoms since 1986, and took high doses of AZT for a year. He then broke off treatment because of muscle and liver problems, and has been on intermittent much lower doses since then. Although Jim's T-cell count hasn't improved overall since he started on AZT, he says it has improved his quality of life.

JIM PRUITT: "I began to feel better. I started gaining weight, the fevers went away, clinically I was doing better. My energy returned. This was not a response that I think everyone experienced with this drug, but my response was very good."

Gordon living in Central London has had no problems with AZT. Because he had developed mouth lesions and had a low blood clotting cells - or patelets - he was prescribed 1000 milligrams of AZT for 18 months. He's now reduced his dose by half.

GORDON: "I do accept that I'm one of the lucky ones. I do of course accept the evidence that it is not a good drug, and that it does have toxicities, which can be quite severe. My attitude would be: find out all you can about it. Ideally talk to someone who has a good experience of the drug, and someone who had a experience of the drug. And then you just have to follow your own instincts."

Cass Mann is a volunteer counsellor for Positively Healthy, the London based self-help group. It provides members with free information about AIDS and different treatments. Does he think AZT improves quality of life?

CASS MANN: "No. That is not true. I have never seen it improve the quality of life. Certainly when people begin the drug, they begin with the best possible motive and expectation, but after a period of time there are of course people who claim it does. But I've known no one who's been on it for an extended period who would claim that."

DR. JOHN HAMILTON: "There has been no formal demonstration of improvement in quality of life. It was assumed that the delay in progression to AIDS would translate into an improved quality of life because it seemed logical and made sense. In fact, the only study that has been done on this point and published to my knowledge has failed to demonstrate an improvement in quality of life."

In the UK and US doctors reference books there are marked differences in the entries about AZT under its brand name Retrovir. For example in the US entry there is a section called 'Information for Patients'. There is no such helpful section in the UK Data Sheet Compendium. In this US section it states that patients should be informed that: 'the drug had been studied for limited periods of time and that long-term safety and efficacy are not know.' Nowhere does this appear in the UK document. There are other omissions and anomalies. Human Rights Lawyer Larry Gostin, director of the American Society of Law and Medicine in Boston, believes AZT can benefit people with AIDS, but that the difference in information is concerned that the difference in information discriminates against people in Britain.

LARRY GOSTIN: "In effect that treats patients in Britain less favourably, and with less respect than patients in the United States. And that is wrong. The drug companies ought to disclose to physicians, and physicians should disclose to patients, all relevant risks, whatever the country maybe, whatever the legal system may be."

In West London, Stuart Marshall is also concerned about the different standards of information. He's a trustee of Positively Healthy. He knows he's been HIV positive for eight and half years, and has always resisted pressure to take AZT. His immune cell or T-cell count has quadrupled over the last four years and is now between five and six hundred.

STUART MARSHALL: "When I was first offered AZT I was told nothing at all about the side effects. I knew a lot about the side effects because of having a lot of information from America about it. It's really my opinion, based on a of personal experiences that people are still not being told about the side effects properly, and therefore I don't think they're able to make a proper informed decision about whether they should take the drug or not."

Currently in the USA, much speculation and concern surrounds possible links between AZT and the emergence of a type of lymphoma or cancer of the blood in the late stages of AIDS. This FDA internal document, describing mutating human cells in an AZT laboratory experiment, says: 'This behaviour is characteristic of tumor cells and suggests that AZT may be a potential carcinogen'. However, Dr. Paul Volberding believes that the lymphomas appearing late in AIDS patients are not associated with AZT.

DR. PAUL VOLBERDING: "The appearance of lymphomas in patients receiving anti-retroviral therapy is a reflection of the longer duration of survival, and the ability to remain alive, and therefore unfortunately, at risk for some of these other complications of HIV disease. So, we see the lymphomas as an unfortunate reflection of our success at this point, rather than a reason for real caution."

We asked Dr. Michael Lange if he was convinced by the explanation that lymphoma is a natural consequence of living longer with AIDS.

DR. MICHAEL LANGE: "No I'm not. The major reason for that is that most, almost all the lymphoma that I have seen was a first AIDS event, and occurred not at the late stages of the disease, but was the diagnosis that was made, that made that patient an AIDS patient. And prior to AZT coming along I never saw lymphoma in people who had had several opportunistic infections as a late stage event."

In October last year, a new anti-AIDS drug called ddI with similar mechanism to AZT was licensed in the United States under the fast track system. in the USA AZT is now being tested on pregnant women. And London's Great Ormond Street Hospital for sick children will soon be part of a European AZT study involving several hundred children and babies. All of this is occurring without any real public debate.

Of course no one should ever change medication whatever the drug without proper medical advice. Many AIDS doctors and carers are convinced that particularly in the later stages of the disease AZT is invaluable. But some of its greatest exponents are only too aware of its limitations.

DR. MARGARET FISCHL: "Does AZT prevent death? No. Does AZT cure AIDS? No. No one ever said it did. It only works by preventing cells from becoming infected. So, therefore it will have limitations and we recognise that and that's why drug development has still surged ahead."

As we've already demonstrated it's arguable whether AZT can actually 'prevent' cells from becoming infected without killing them as well. So, what are we left with? At best its supporters argue that AZT can delay progression to full blown AIDS. Albeit with side effects.

DR. PAUL VOLBERDING: "I think the question is one of starting the drug before the patient becomes so advanced that the side effects become intolerable. But in terms of long-term administration, I think when the contrast is taking a drug that has some possibility of toxicity, versus the certainty of disease progression without the drug, I think most people make the understandable decision to try drug therapy."

But critics of AZT argue that the benefit is not proven.

DR. MICHAEL LANGE: "I would say in most cases, or in a number of cases, you do see a small increase in T4-cells during the first three to four months. Usually by six to nine months, if you are lucky by twelve months, you're back to where you started from. And from there on there's in most cases a general decline so that you end up with T4-cells less than beforehand."

Resistance to calls for more open debate about AZT has come from the US FDA, the medical profession, and the pharmaceutical industry. The FDA and Burroughs Wellcome in the United States, two doctors running the current UK Concorde trial, and the Wellcome Foundation in the UK, have all refused to take part in this programme. Wellcome UK said this was because they didn't believe we would be sufficiently balanced and objective in our approach to the subject of AZT to make a reasonable programme about it. Last week Wellcome made another announcement encouraging the wider use of AZT. This letter issued to doctors in the UK describes favourable results from a trial in ten countries involving nearly 1000 HIV positives without very low immune cell counts. But the doctors have been approached before details of the trial have been published in a scientific journal.

In the UK there has been negligible coverage of the issues surrounding AZT. In the USA however more voices have been raised. Florida's Miami Herald has kept up a spirited attack on the AZT establishment through journalist Elinor Burkett.

ELINOR BURKETT: "The reaction almost universally in the research community and the patient community was hysteria. There was tremendous sense that I think has happened to journalists all over the world, that by writing such an article, I was being socially irresponsible because I was going to make a group of very sick people stop taking their medication. The fundamental truth of the American research establishment is that the scientific community feels that it shouldn't have to answer to the rest of us. So, the notion that a non-scientist would go in and question the research that they used, the accuracy of their data, and the truth of their interpretation, provoked a tremendous controversy throughout the research establishment."

CELIA FARBER: "I think there's a terrific arrogance. I think there's always been an arrogance on the part of the medical establishment. They believe themselves to know everything, and once they've made up their minds about something they're very unwilling to change it."

Dispatches has been advised by leading counsel that the false and misleading claims about AZT described in this programme could amount to a breach of the Medicines Act, which if successfully prosecuted would constitute a criminal offence. Dispatches is sending a dossier of relevant information to the Medicines Control Agency at the Department of Health.