WHAT'S HAPPENING WITH AZT?

Four months ago when this column first reported on AZT, the problem was digging out the information. Now the problem is digging out from under the avalanche of press coverage released by a public-relations juggernaut that may be unprecedented in medical history. The current campaign for AZT involves a major drug company, several agencies and branches of the Federal government,
and a number of major medical centers -- all working in a concerted push planned months ago, even before the test results were in.

The dilemma around AZT is that the best information now existing is the results of the recent study in which 145 persons with AIDS took AZT (and 137 others received the placebo, or dummy pill, in the "double blind" trial). Yet physicians, reporters, or independent scientists cannot see these results; they only hear those conclusions which the institutions pushing AZT choose
to release. The first scientific report may be weeks or months away (we have heard that the writing has just started). So for now, persons with AIDS and their physicians may have to make decisions based on what amounts to little more than press releases, plus a 15-page protocol giving treatment information for physicians.

Why not simply trust the experts who have the information, and the recommendations and policies they publish? Because no one familiar with how AIDS has been handled could reasonably trust the authorities with his or her life. Remember that the last officially announced miracle was suramin, which was a disaster in the trials.

The past behavior of the "AZT juggernaut" also does not inspire confidence:

* The government,corporate, university combine behind AZT blacked out all reference to previous antiviral work with the compound, effectively concealing this information from the scientific community. Several papers mentioning antiviral laboratory tests of AZT were published eight years ago, but researchers are unlikely to find them without references.

The references are available from this writer who, incidentally, sat on this information for several months to avoid any risk of damaging the AZT campaign by embarrassing it before it had acquired economic and political momentum.

* The conduct of the double-blind trials did not show compassion for the patients. We are particularly appalled by the admitted fact that much of the reason for denying AZT to practically everybody with AIDS was to force several hundred subjects into the double-blind trials (which the experimenters believed no one would have entered if they had other access to the drug). We
also question whether double-blind trials were necessary at all in this case, since it was clear, even before the trials began, that AZT was helpful; see the study in THE LANCET, March 15, 1986, as well as anecdotal press reports. (We believe that double-blind experiments are both scientifically and ethically appropriate only when the experimenters really don't know which
of two options is better.) For an in-depth report on the ethical issues of the AZT trials, see the article by Denise Grady in DISCOVER magazine, August 1986.

* It may be coincidental, but informal information channels on AZT seem to be drying up at this time. Also perhaps coincidentally, a lot of competing information is being kept out of the news.

(This problem goes far beyond AZT. Scientists who want to publish their results or want to be funded in the future, or drug companies who want Federal approval for their products, are both highly vulnerable and therefore easily pressured. Medical journals want results kept secret until they get around to publishing them, so that, at publication, it will make news. Government
officials don't want political pressure, or anguished calls from the public that complicate their lives. Scientists and corporations -- both competitive -- don't want their rivals to overshadow them in public attention. For all these reasons, insiders enter into a virtual conspiracy to keep the public in the dark about important news; they justify their actions as
avoiding "false hopes" until they have done "more research", which may take years.

This writer, too, has withheld important treatment news, when the scientists feared that if it leaked out in the press, major medical journals would refuse to publish it, regardless of merit. Then their results would be effectively lost, not taken seriously by the medical establishment, and therefore not used for treating AIDS at this time.

This system of concealment prevents patients and their physicians from knowing about promising treatment possibilities, many of which would certainly be tried if the available information were considered and the patient's interest were put first.)

What Is Known About AZT?

AZT does look like the best treatment news in a long time. We know that it can help some people, though it is not a cure. And we know that its use involves serious risks, though we don't know how serious.

AZT is a simple chemical compound; it closely resembles another chemical which is a normal component of DNA, the substance which carries the genetic code of living things. AZT enters the cell (including brain cells, since it crosses the blood-brain barrier), and interferes with a key step in the reproduction of a certain kind of virus, (the retrovirus), of
which the AIDS virus is one example. A retrovirus, unlike almost all other life forms including other viruses, does not contain any DNA. Instead, its genetic information is in RNA, and this information must be transcribed into DNA by an unusual process inside the cell. AZT interferes with this process, apparently by providing false building blocks which get incorporated into the
DNA being created by the virus.

AZT slows or stops the reproduction of the virus, but does not kill it. So AZT is not a cure for AIDS, but must be taken indefinitely until something better is found.

Fortunately, however, the fact that AZT only inhibits the virus does not mean that it only keeps AIDS from getting worse. Most people who used AZT had significant or major improvement -- including weight gain, clearing up or prevention of opportunistic infections, improvement in T-cell counts, and generally feeling better. In the latest trial, 17 patients in the placebo group died but only one in the AZT group died.

How bad are the side effects? We have heard contradictory reports. The main problem seems to be anemia and bone-marrow damage, which can be severe in some cases. At press time, this writer has not found out how well physicians have learned to control these problems -- by using smaller doses, doing blood tests for early warning, or in other ways. A spokesperson at the
official hotline (see number below) justified the strict controls being placed on the use of AZT by calling it a "highly toxic experimental drug".

There is also concern that AZT might cause long-range problems which have not yet manifested, especially since it might affect human DNA. Apparently this worst-case scenario is just a theoretical concern at this time; and as long as AZT is used only by those who are already seriously ill and would probably die without it, this possibility doesn't seem like a big worry. But any future move to use AZT as a preventive measure for the
millions of people who have been exposed to AIDS but are still well, must be scrutinized very carefully.

Researchers are trying new compounds which might be similar to AZT, but are less toxic. However, these new chemicals have had little or no human testing yet.

How To Get AZT

To find out more about AZT, patients and physicians can call a toll-free hotline at the National Institutes of Health, (800) 843-9388, from 5 am to 9 pm, Pacific time. Meanwhile, here is what we have heard:

* At this time only persons who have had pneumocystis will be allowed to receive AZT. The drug will be provided without charge, under a special plan for greatly expanding the ongoing clinical trials. It is believed that about six thousand people with AIDS will be eligible to get AZT under this rule.

* The patient must not currently be getting any other drug for an AIDS related condition, or cancer chemotherapy, or any drug which could harm the kidney or bone marrow. He or she must have healthy kidneys, liver, and bone marrow. There may be some requirements for red and white blood cell counts.

* Children under 12, pregnant or nursing women, or women taking birth control pills will be excluded at this time.

* Any medical doctor can prescribe AZT. However, the doctor must first submit special forms, including proof that the patient has had pneumocystis. Then the AZT will be shipped to a nearby pharmacy. To start this process, the doctor can ask for a packet of forms from the hotline number given above.

* We have heard conflicting reports about when AZT will be made available to persons with opportunistic infections other than pneumocystis. One leading researcher was quoted as saying that would happen when greater supplies were available. But the AZT hotline denied that supply was an issue, and said that AZT was being made available to persons with pneumocystis now because patients had shown statistically significant greater survival
time, and that it could be made available to persons with other opportunistic infections when other studies had been completed.

Discussion

* The exclusion of persons with KS, but not pneumocystis, may not be as arbitrary as it sounds. In the earliest AZT trial (the study in THE LANCET cited earlier), most patients with KS got worse or did not improve. But this study involved only a handful of patients, so there should be more testing.

* We need detailed reports of the new study just completed, but not yet published. With 145 persons on AZT, and 137 on the placebo, information must have come to light on opportunistic infections other than pneumocystis, and perhaps on KS also.

* We have seen repeatedly that treatment research will seldom move unless there is political pressure. In the near future we will urgently need to make sure that AZT is made available to others who should have it, especially those with serious ARC such as toxoplasmosis, meningitis, or infection of the brain by the AIDS virus. Often no conventional treatment has worked
for these people. There is no excuse to wait for a new study, which could take months just to set up, when all available evidence supports the use of AZT.

* We are hearing recent reports that the AIDS virus does not kill nerve cells when it infects the brain, so the damage might be reversible if the virus could be stopped. Since AZT is known to halt reproduction of the virus, to bring major clinical improvement to some people, and to cross the blood-brain barrier, why not let persons try it now when there are neurological complications and no other treatment is effective, instead of
handing these people a death sentence?

If the decision makers need more evidence, they can have a researcher spend a few days comparing the records of the 145 AIDS patients who received AZT with those of the other 137 who got the placebo. Although all these subjects were chosen for the trial because they had had pneumocystis, some of them must surely have developed neurological problems also -- in the placebo group at
least.

* The case of the AZT trials shows once again that the division between AIDS and ARC is arbitrary and not medically justified. It serves mainly as a bureaucratic excuse to deny people the help they need.

* The availability of AZT, the first AIDS treatment considered effective by conventional medicine, must not be allowed to hamper the development of other experimental or alternative treatments. Remember that the development of antibiotics did not stop with penicillin -- and AZT is far less effective than penicillin was.

* The use and control of AZT will raise privacy issues, especially for the large number of doctors and patients who have not officially been reporting AIDS. Fortunately, the names of patients receiving AZT will not go to Washington; only code numbers will be used. The local pharmacies will know the patients' names, however.

* A number of practical questions still need answers. How long should one continue taking AZT if it doesn't seem to be helping? Are there any problems with stopping its use? Users will need to wake up in the middle of every night to take a pill, in order to maintain blood levels of the drug; is this requirement really worth it for patients who should get good rest and reduce stress levels? Will doses, etc., be set and changed
entirely for the patient's benefit, or also for purposes of collecting clean data? Some of these questions may be answered in the treatment protocol for doctors, available through the hotline number above.

A Personal Note

After following AZT for several months, what would this writer do? Would I use AZT?

If I needed it, yes. If I had had pneumocystis, probably yes, but it would depend on my condition, history, etc. The difference in death rates in the double-blind trial, the published results of the earlier trial, and the anecdotal results which have leaked out of these studies, are all impressive.

But whether or not I qualified for or used AZT, I would also look closely at other experimental treatments: DNCB, AL 721, ribavirin and isoprinosine, naltrexone (see future article), and BHT, more or less in that order. Information on DNCB, in particular, indicates that this treatment might be especially valuable to those least helped by an antiviral such as AZT; see our article on DNCB, September 26, 1986.

I would also look closely at diet, vitamins, and herbs; at physical exercise; at avoiding drugs, intestinal parasites, and other illnesses; and at attitudinal and spiritual healing, through affirmations, visualization, or whatever worked best for me. I would attend AIDS/ARC support groups.

At this time, AZT shows more proven benefit that any other single treatment -- partly, at least, because it has been tested more. But we do know for sure that it is not a cure. It has not made anything else obsolete, nor has it overcome the need for individuals to learn about treatments and take responsibility for putting together a total program that works for them.

Toward that end, this column will continue to point out the treatment options which appear most promising -- whether they are experimental, alternative, or conventional -- and to report on the scientific background behind them, and on the experiences of their users.