When was azt invented

On the 30 th anniversary of this milestone, Time magazine takes a look at the story behind the controversial med azidothymidine, commonly known as AZT. Also known as Retrovir or zidovudine, the compound AZT was not originally created with HIV in mind but was developed in the s to battle cancer.

To fast-track the med, the drugmaker conducted a trial with people who had AIDS. After 16 weeks, it was halted because those taking AZT were doing so much better than those not on the med. The results were considered a breakthrough, and the FDA approved the drug on March 19, , in a record 20 months, according to Time. The approval was granted despite many questions remaining unanswered—for example, how long did the benefits last?

In fact, Time notes, the trail remains controversial today. The plan was to randomly assign the participants to take capsules of the agent or a sugar pill for six months. Neither the doctor nor the patient would know whether they were on the drug or not.

After 16 weeks, Burroughs Wellcome announced that they were stopping the trial because there was strong evidence that the compound appeared to be working. One group had only one death. Even in that short period, the other group had But the study remains controversial. For example, some patients received blood transfusions to help their immune systems; introducing new, healthy blood and immune cells could have helped these patients battle the virus better.

There were also stories of patients from the 12 centers where the study was conducted pooling their pills, to better the chances that they would get at least some of the drug rather than just placebos.

And there were still plenty of questions left unanswered about the drug when it was approved. How long did the apparent benefits last? Did they benefit more than those further along in their disease? The people in the trial were already pressuring the company and the FDA to simply release the drug — if there were something that worked against HIV, they said, then it was not ethical to withhold it. I said that that was the trap that everyone was falling into.

The AZT will work for you for a little while, for the maximum of one year, as it did for me, and afterwards the damage became visible. It is hard to think of another product that is so dominant in its field. You read the showbiz autobiographies and those three little letters snap out of the page. He agreed. That may be why some people, including a few reporters, concluded that I was sicker than I actually was.

Somebody advised him to drink all his blood and replace it with new blood. Rudi lost his temper and said: 'I want this medicine. But I had to give in and prescribe it - he was so insistent. But he didn't take it regularly. He went off every time with tons of drugs, and every time I went to see him I found unused packets all over the place.

It stops the virus replicating. At the beginning they gave people much too massive doses, which affected us physically. I had no recognisable toxic side-effects from it. I began taking it in September , I think, and I came off it last August. We've never discussed it since. The whole thing is so complicated, because I took a lot of other drugs as well. And then obviously if I got an infection there was fluconazole and all of that area.

And then at a certain point they added hydrocortisone and fludrocortisone to keep my energy up. Jarman has recently been in hospital. I've had a skin complaint and they decided it would be very sensible to take me off all my pills, and then go back on the drugs to see if they were causing the skin complaint. They can obviously play around with the drugs. You can say that if it helps someone psychologically then it must be doing some good.

I think the doctors generally feel that it does some good. But how do you know? Retrovir, the drug's brand name, accounts for more than 13 per cent of its total income, and yielded pounds m last year. As the only big earner to have been launched by the company in the past decade, the continued success of AZT is crucial to its growth.

The company will be well aware that at the end of last year the World Health Organisation estimated that about 13 million men, women and children have been infected with HIV since the start of the pandemic. Part of the Wellcome Foundation was floated on the stock market in , the year of the AZT breakthrough. Subsequent rises in share prices have been directly linked to the fortunes of the drug and the results of new trials.

In February , the share price jumped By November the share price had almost doubled to p; year-on-year pre-tax profits were up 28 per cent to pounds m. In early , the share price was at p; last year's pre-tax profits were pounds m. It was just this emotive demand that led to the picketing of the Wellcome shareholders' meeting in January Activists complained about the price of AZT, and what they saw as Wellcome's reluctance to provide all available information on the drug. Wellcome shareholders were irritated by this intrusion, not least when Act Up members interrupted the meeting and insisted on talking to Sir Alfred Shepperd, the outgoing chairman.

But Wellcome executives were baffled: they believed they had done everything they could to benefit people with HIV and Aids, certainly more than any other pharmaceuticals company. Was it not these very same activists who had celebrated when AZT was launched three years earlier?

At first Wellcome defended its pricing on. The recommended dosage was also reduced for medical reasons, which meant many more people could tolerate its toxicity. Today AZT costs about dollars 3, per person per year, or about pounds 2, As would be expected, Wellcome plays up the good news.

When, in , two double- blind placebo trials of the effects of AZT on asymptomatic and less seriously ill patients showed that it could delay the progression of the disease, much was made of the results and the share price rose by 30p.

But when, four months later, the company admitted that AZT had caused cancer in rodents, it explained that the rats and mice were given 10 times the dose prescribed to humans, and that several other drugs in use by humans had also produced tumours in animals when administered over long periods. Wellcome's share price went down one penny. Wellcome's PR machine is an impressive force, and much money is spent on convincing the media of AZT's worth. You go and see them and you get a lot of bumph: how AZT works, why it is more effective than other anti- retrovirals.

Wellcome house-magazines talk of the extra , productive years of life it has made possible through the drug, about how many thorough and independent studies have stressed AZT's efficacy. The day-to-day therapy of the patient is not our responsibility. But about three years ago we started to open our labs to people with HIV and their carers, contrary to the advice of my security and other colleagues.

You then realise the uncertainty and the frustrations involved in that act of taking a tablet for the very first time. When people with HIV came through the door of the lab I could almost touch their anger.

But I realised that the anger was not really about Wellcome or me, but about their mortality. They were frustrated, and saying, 'Please, please what can I do? Dr Jones is one of the few pharmaceutical industry representatives on Britain's Medical Controls Agency. Wellcome has clearly selected its spokesman with care. Otherwise we look like ogres and robber barons all the time. That's the whole history of our business; if you've got a problem with a product, you must, you must, you must tell people.

The criticism hurts a lot; our integrity as a scientific body is important to us. I don't take too kindly to people saying, 'Oh, you don't want to listen to Wellcome, because they would say that, wouldn't they?

You have to believe that the integrity of science is good. Jones has had a bad few weeks. Wellcome's share price was hammered by last month's Concorde trial report, falling 10 per cent to p, before rallying to p.

Five days after the report appeared, Wellcome staged a damage limitation exercise, at which Jones told a press conference that he was unhappy with the way the results were released, without peer review or advice to patients, and saying it had caused panic among those with HIV.

He said that the full results had yet to be released, and hoped that a more beneficial picture of early intervention with AZT would emerge at the ninth International Aids Conference in Berlin in June. He also outlined that the protocol of the study had changed from that agreed in When an American study reported in that AZT did have beneficial effects on people with asymptomatic HIV, the Concorde officials decided that people on its trial could switch to AZT if they wanted to; this may have led to a diluting of the results.

Last week, Jones reiterated why AZT may still be beneficial, and why doctors should continue to prescribe the drug early. Five of these are control studies with placebos, and five are cohort studies, in which we simply give the drug and observe what happens.

These studies involved more than 6, patients and ranged from one to four years in duration. We believe we have accrued sufficient data to show that taking the drug when you're asymptomatic does delay the onset of further symptoms. For the launch conference in London, journalists flew in from all over Europe to hear Wellcome executives describe how pounds 1m was being distributed to many educational organisations.

An emotional climax of sorts was provided by Jerry Breitman, the company's US director of professional relations. He was there to present the 'workplace initiative', and his speech contained a little surprise at the end. Like the wig salesman whose coup de grace is to rip off his own toupee, Breitman declared himself HIV-positive.

It is, truly, one of the best decisions I have made in a very long time. One of the initiatives raised was Wellcome's involvement with the Terrence Higgins Trust. This first surfaced in , with the publication of four information leaflets.

Two months ago staff at the Trust and volunteers read in their newsletter that the link had been strengthened. The newsletter explained that 'THT, along with the Wellcome Foundation, is about to begin producing an important new medical information series. THT are providing a series of medical updates for all staff and volunteers. We will be providing them on a regular basis every two months in the evening. Costs will be met by the Wellcome Foundation, which also funds our series of general booklets.

Nick Partridge, chief executive of the trust, is dubbed 'Nick the Sick' on the placards carried by the protesters outside his office. We would be neglecting our duty if we were not in regular contact with Wellcome, Bristol-Myers Squibb and Roche, arguing for greater investment in HIV research and fair and balanced information.

The leaflets are not about treatment issues. But once they were. In the trust produced a page booklet on HIV and its treatment; nine pages were devoted to AZT, but only half a page was given to other therapies.

The copyright on the leaflet was held by the Wellcome Foundation, which also paid for its printing. The main fault of that leaflet is that it is too hopeful. By the hopes around early intervention had probably gone further than we realise, in retrospect, was wise. The desire by many people with HIV to say, 'Yes, we can live with this infection' meant that a lot of hope was invested in the theory of early intervention.

For all its faults, our leaflet was still a lot more realistic than the material that Wellcome was putting out on its own. Remember that over the years, there have been many stories of breakthroughs that proved to be wildly optimistic.

AZT is the future that was; no one believes in the 'magic bullet' any more. It does have benefits for some patients who are seriously ill, but there is now severe doubt over its other uses. This, after the drug has been subjected to more tests, and has been the subject of more post-launch research papers, than perhaps any other modern therapy.

Several trials are in progress. Two weeks ago it was announced that Wellcome has joined forces with its competitors Hoffman-La Roche, Bristol-Myers Squibb, Glaxo, SmithKline Beecham and 15 other companies, in an attempt to pool their research knowledge and find an effective treatment. Wellcome is also developing some other anti-Aids drugs on its own. We won't hear about these for a while; the company doesn't want to raise any hopes.