MONTREAL CONFERENCE: OVERVIEW AND COMMENT

The "V International Conference on AIDS", June 4-9 in Montreal, was the major AIDS conference of 1989. We have found it difficult to cover this meeting.

Why the difficulty? With over 5,000 papers on AIDS presented, we could easily have filled several issues with interesting facts and stories, each one safely documented. But these would have been isolated stories with no particular use or relevance. We want to present this information within a meaningful framework.

The widespread myth of objectivity, a myth cultivated to support the status quo, has obscured the fact that viewpoints, interpretations, or relationships can be an essential tools for effective communication, not just extraneous opinion. The lack of coherent, well-formed viewpoints explains the seeming paradox of having simultaneously too little AIDS information, and too much. Persons seeking information are flooded with unconnected facts but unable to find what they need.

It is hard to cover the Montreal conference because viewpoints must be constructed for this purpose. No single theme emerged.

As many as fifteen official meetings ran simultaneously, together with hundreds of poster presentations, as well as press conferences and private or miscellaneous meetings. We had to choose certain areas, and leave important subjects to others. We did not focus on AZT, for example, because we knew that many physicians would be paying close attention to this treatment, and therefore important developments would probably not be lost. Instead, we sought information which could be overlooked by the mainstream, but which the AIDS community might use to save lives.

Several different themes emerged as most important:

(1) Lack of progress on getting new drugs ready to use;

(2) Promising drugs in the research/approval pipeline;

(3) More information (mostly negative) on certain "alternative" treatments;

(4) New treatment ideas; and

(5) Access issues, including early treatment and developing countries.


Lack of Progress

The central impression from the conference is disappointment at the lack of productivity of the clinical-trial system during the last several years. Dozens of promising drugs are in the research/regulatory pipeline; the problem is getting them out of the pipeline.

Two years ago, when the same conference was held in Washington, D.C., some of the AIDS physicians said, "Next year, in Stockholm." A year ago, after the Stockholm conference, it was, "Maybe next year, in Montreal." This time we did not hear the same expectations for the 1990 conference in San Francisco. The experimental drugs are more promising than ever. But people are learning that the research designs now in use could not possibly release important antivirals for years even when we already have every reason to believe that the drugs are safe and probably will make an important contribution to therapy.

The world according to press releases designed by publicrelations professionals is a world where everybody involved shares a sense of urgency, and is proceeding as fast as good science will allow, but no faster. In this world, new treatments could appear almost any time, as if by magic. But a look behind the press releases at the actual design and operation of clinical trials shows clearly that there will be no decisive advances in AIDS treatments by the 1990 San Francisco conference, or the 1991 Florence conference either, if the design and management of trials continues as it is going today.

Fortunately, the impediments to productivity are becoming more clear. Our article below ("Why No Antivirals: A Case History of Failed Trial Design") analyzes as a case history an upcoming trial of the major antiviral which is furthest ahead in the clinical-trials pipeline. We show why it would be almost impossible for this drug (or any other major antiviral) to be ready within two years, even though there are dozens of candidate drugs which appear promising in laboratory, animal, and even human studies unless a widespread professional consensus about how to design trials of AIDS drugs can be changed. We show why the trial was designed the way it was (making rapid results impossible), what assumptions motivated this design, where those assumptions are wrong, and what can be done instead (or in addition).

The central problem is not with any one agency, company, or other institution, but with a professional consensus which crosses organizational boundaries and if not changed, will stop any decisive treatment advance from being available for years. Instead of waiting until the 1991 Florence conference, for example, to ask once again why there are no new antivirals to replace or supplement AZT, we can raise the issue now. Some of the failures of upcoming trials are so predictable that we can analyze them before the trials even begin when some of the problems might be bypassed or avoided instead of waiting years to only recount the same failures after they have happened.

The professional consensus which guarantees lack of results has been allowed to persist because of national and international lack of leadership on treatment development, lack of commitment to saving lives. In the United States, for example, 97 percent of the 5,100 largest foundations have not given one penny to AIDS (December 1988 report of the Foundation Center, cited in May 17 talk by Dr. Timothy Wolfred, outgoing executive director of the San Francisco AIDS Foundation); of the three percent which have contributed at all, it is well known that most will not touch research or research advocacy. This lack of commitment, so clearly seen in the above tabulation, operates less openly behind the technical complexities of human trials, the legitimate need for caution and control in human research, the cleverly concocted press releases, and the widespread lazy assumption that the experts know best and therefore no further thinking or action by anyone else is necessary.

It is understandable that people and institutions are reluctant to look closely at clinical trials, a complex, technical area where human life is at stake. But in the resulting vacuum, the failure of national leadership and commitment has combined with pre- existing problems in the medical and research systems to lead to a "conventional wisdom" which includes assumptions which guarantee that the clinical-research system will fail to respond to the AIDS public-health emergency.

Something can be done. When the AIDS community is well informed, it can bring key issues into the open and force them to be addressed. Our "Why No Antivirals" article, below, shows the precise errors and design flaws which guarantee that an upcoming clinical trial will fail to meet the needs of the AIDS emergency, no matter what happens in the trial. Since this study is one of the better ones, and since the drug itself is ahead of all the important antivirals in the regulatory pipeline, the flawed assumptions and design illustrated in this trial almost guarantee that no decisive advance in AIDS treatment will be available for years even though the drugs which will be available then are in many cases already well known today.

This issue has not been widely understood; until the Montreal conference, we ourselves did not see it clearly. By detailed understanding and by persistence, the AIDS community can force key weaknesses in trial design and administration to be addressed, force the spokespersons for the conventional wisdom to state the case for their positions before other medical and research professionals. When their case is weak, the professional consensus which controls clinical research will shift, and much faster shepherding of drugs through the research and regulatory system can quickly become possible.


Outline on Promising Treatments

Many attenders at the Montreal conference (including this writer) agreed that DDI may be the most important single drug in the AIDS research pipeline now. Most of the information presented was not new, but confirmed previous informal accounts (see "DDI Information Published", AIDS TREATMENT NEWS # 78, May 5, 1989). We are still analyzing the conference information, and will follow DDI closely in the future.

Compound Q was not discussed at the conference, although one abstract was published (abstract number C.596).

Soluble CD4 received much favorable attention in talks by Robert Gallo, M.D., and other researchers. So far, however, the efficacy results have been disappointing. While we are not listing this treatment as one of the most promising, some of the scientists who have worked with it remain enthusiastic about this line of research, especially later generations of the drug.

Two posters were presented and three other abstracts were published on hypericin, which continues to look good, although it received little attention at the conference. No human results were included, since no human research has yet been completed.

There were many posters on treatment of opportunistic infections. Except for pneumocystis prophylaxis, the most important single drug was probably fluconazole, a broad- spectrum antifungal used in Europe but still not marketed in the United States.

We will report further on promising treatments in future issues.


New Information On Non-Approved Treatments

Treatment possibilities which look less attractive now than they did before the Montreal conference include ribavirin, isoprinosine, dextran sulfate, AL 721, and roxithromycin. Often the new information is ambiguous, so we want to study it further before writing a report. We cover roxithromycin, which failed in treating advanced toxoplasmosis, below.

New Treatment Ideas

A number of new ideas were presented, especially in some of the poster presentations.

For example, scientists at the University of Pittsburgh tested an organic arsenic compound which had been used to treat syphilis before penicillin was available (abstract number M.C.P.133). The compound, oxophenarsine, was found to be extremely effective against HIV in the test tube, in concentrations as low as 0.035 micrograms/ml. According to one of the presenters whom we met at the poster, it is the only drug known to be able to block the virus in chronically-infected H9 cells. In a similar test, AZT showed no antiviral effect.

We asked about toxicity, as some of the early syphilis treatments were notorious. This one was apparently not as bad as some of the others.

One advantage of this drug, which was once FDA approved, is that much information about human use is already available, published in old medical journals.

Unfortunately no pharmaceutical company anywhere still manufactures this drug, which was used by injection. The Pittsburgh scientists are trying to get the original manufacturer to produce enough for a test. Since the original patent rights have long since expired, other companies could legally do so; the drug is easy to make. (The University of Pittsburgh has applied for a use patent for HIV treatment, in order to make the project attractive to investors and obtain financial support.)

Oxophenarsine could be tested quickly and inexpensively to see if it might be helpful as an AIDS antiviral. Unfortunately it is more likely to be overlooked and ignored, regardless of merit. Few people have both the capability and incentive to make anything happen toward getting this potential treatment tested. We hope that this article will bring the drug and the project for its development to wider attention.