&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& Copyright 1993 by John S. James; permission granted for non-commercial use. AIDS TREATMENT NEWS Issue #180, August 6, 1993 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: [items are separated by "*****" for this display] Research, Political Leaders Plan Future Directions Prophylaxis: New One-Day Sulfa Desensitization Procedure FDA Nutritional Supplement Regulations: Comments Due Aug. 17 National AIDS Lobby Days, Washington, D. C., September 12-14 In Memoriam: Larry Waites, M. D. ***** Research, Political Leaders Plan Future Directions by John S. James A high-level meeting on "Future Directions in AIDS Research," July 30 and 31 in Madison, Wisconsin, studied how to improve the AIDS research process, especially how to move practical treatment ideas from the laboratory to the clinic. Participants included: David Kessler, M. D., Commissioner of the U. S. Food and Drug Administration; Anthony Fauci, M. D., Director of the U. S. National Institute of Allergy and Infectious Diseases; Samuel Broder, M. D., Director of the U. S. National Cancer Institute; Robert Gallo, M. D., head of the Laboratory of Tumor Cell Biology of the National Cancer Institute; Kristine Gebbie, the new White House AIDS Policy Coordinator, who starts work August 2; John Niblack, M. D., from the new Intercompany Collaboration for AIDS Drug Development, and Pfizer Inc. ; activists Larry Kramer, Mark Harrington, and Martin Delaney; and over 40 other scientists, officials, and community representatives. The Harvard AIDS Institute, the University of Wisconsin, and Project Inform organized the meeting, which was chaired by June Osborne, M. D., formerly chair of the National Commission on AIDS. Nine points of consensus which emerged are reprinted below. In about two months, the group will meet again to develop more detailed recommendations on scientific directions. The meeting itself was closed to the press, so that participants could explore ideas without fear of statements being quoted out of context. But as the meeting ended, a press conference was held in Madison; AIDS TREATMENT NEWS attended by phone. Reporters' questions were answered by a panel of participants, including: Max Essex, D. V. M., Ph.D., and Richard Marlink, M. D., both of Harvard AIDS Institute; David Pauza, Ph.D., University of Wisconsin, Madison; Dr. Robert Gallo; Kristine Gebbie; Steve Morin, Ph.D., on the staff of Representative Nancy Pelosi (Democrat, San Francisco) on the House Appropriations Committee; Mark Milano of ACT UP/New York (representing the Barbara McClintock Project to Cure AIDS); Larry Kramer; and Martin Delaney. Because of the importance of the meeting and the subjects discussed, we are including extensive quotes from the press conference, to give readers a sense of the leading thinking today about what should be done differently in AIDS and other biomedical research in the future. We have occasionally cut or edited the following quotes. Dr. David Pauza (from his opening statement to the press conference): The future of AIDS is unpredictable. AIDS is a rapidly moving epidemic that is constantly evolving new clinical challenges, and it will impact at catastrophic levels on our personal, social, and economic structures. The number of AIDS cases creates a reservoir for evolving infectious agents under conditions that have not previously been encountered... Furthermore, continued AIDS research benefits all biomedical research, because it continues to create insights not only into this very important area, but into other areas as well. Therefore the first main conclusion of our meeting is that AIDS is special. We believe that effective treatments will be discovered. And we are committed to the belief that it is possible to develop new therapies within a reasonable time, which are capable of providing long-term survival without clinical symptoms...It is not unfair to characterize this as an historic meeting, that begins a new process to reinvigorate our fight against this disease. Dr. Richard Marlink: The meeting drew together individuals from academia, government, regulatory agencies, and many of the key basic scientists, both in and outside of the government, in a think-tank type session on how we look at our scientific research priorities as a nation, and how can we better implement them; where can we do better, how can we do better, focusing on the future. A unanimous consensus from the group was that in the future, the disease from HIV will be preventable -- those infected with HIV eventually will have treatment that will prevent disease. That sounds pretty simple. But most of us in AIDS research and the AIDS community went away from our recent international meeting in Berlin with feelings of frustration and depression. Many times it was portrayed in the media, and at the meeting, that we weren't getting anywhere in this fight. With this present meeting, our gut feelings and scientific opinions are that AIDS will eventually be treatable, so that people will be able to live with HIV infection without having disease. I think the most important consensus conclusion follows. That is, since AIDS could be fully treatable in the future, it's only insufficient resources that inhibit our pace, both in basic bio-medical research and in AIDS research. It's insufficient resources that prevent this treatment from coming about. Martin Delaney: We will continue what we started here in a second meeting within two months from now. Today we reached consensus on two areas. One was a list of the principal priorities of AIDS research on a scientific basis, and a document will be available about that. For those who follow this disease, there will not be any great surprises; we have known for many years what those priorities and most critical issues are. The other area is a list of nine consensus statements that affect not only scientific issues, but policy issues around the management of AIDS research, the identification of gaps and discontinuities within existing programs, the potential for the development of targeted special new research programs and mechanisms of prioritizing issues for treatment in special fashion, the development of improved communication and coordination methods, a look at new management methodologies and technologies for use within some of the existing programs, and ways to create greater collaboration between private industry and government in AIDS research. These are not yet in the form of specific concrete proposals, which is why there is a later meeting. What we consensed on at this point was an identification of the areas that we were choosing to produce a specific targeted document, which will have the concrete recommendations in terms of policies and programs. People will continue to work on these consensus statements and bring specific proposals for implementing them to the coming meeting. Question: Were there any new ideas about how to break down barriers between corporate entities that may be developing certain treatments or vaccines in parallel with other companies? Martin Delaney: Dr. Kessler at the meeting was a great help in discussing that, as was a representative of the new consortium of pharmaceutical companies that are attempting to work together in AIDS. We plan to work between now and the next meeting to draw up a proposal. Both government and industry thought that it should be possible to break those barriers down by joint agreements, working through some kind of a collaborative association of government and industry. It was identified as an issue, and a commitment was made to resolving it, and the right parties are at the table. We have agreed to include several more representatives of the pharmaceutical industry at our next meeting. Question: We identified our first problem as a lack of funding. How much money do we need per year, and where do we intend to get it? Larry Kramer: We're trying to come up with new concepts of how to deal with research and how to get the research funded. We realize that we cannot expect the U. S. government to take care of all of this, certainly not with any dispatch. So we're trying to think of ways to lay off different projects to different parts of affected communities. Much money is already being raised for AIDS research in the gay and AIDS community -- through organizations like AmFAR, Broadway Cares, DIFFA, GMHC, etc., as well as various foundations that have money left specifically for AIDS research. We need to build a consortium to get some projects funded by the government, some by the pharmaceutical companies, and some by these organizations. We're trying to find a way to package it, with each package funded by a different part of the community, which could feel that they were buying into a Manhattan Project. This weekend is one of the most exciting couple of days I have spent in over 10 years of going to these kinds of meetings. I have rarely seen so many disparate participants in fighting this plague all in one room and getting along with each other, interacting, sharing information, brainstorming, bull-sessioning, criticizing, and laughing, a camaraderie which has not been in existence since the beginning. Martin Delaney: We're looking at ways to marshal a more organized private response to AIDS in addition to, and in support of, the money the government spends on AIDS. There are parallels historically, such as the March of Dimes from the 1950s, or the American Cancer Society, that have done this in a much larger and more organized way than we've had in AIDS until this time. This is not the formation of an organization yet; at this point it is an idea that's on the table. We want to bring more partnership between private resources and public resources to this problem; we also want to bring more public resources. Dr. Steve Morin: In the House version of the bill for fiscal 1994, there is 1.3 billion dollars for the AIDS research program at NIH. This is a 21 percent increase, and gives hopes about a new priority for AIDS research in the Federal government. Much of the focus of this meeting, however, was on how best to accelerate the AIDS research program, not just government sponsored, but research that's going on through private industry, and through money raised by other sources -- for trying to be more effective for the money that is being spent on AIDS research. This was also a very optimistic meeting; from the participants, there was a real appreciation of the urgency of this issue, the opportunities in AIDS research, and the possibilities of what could be done. With that excitement, there comes a hope of increased resources being dedicated to the AIDS effort. David Pauza: Our message is two-fold. We need to maintain a priority on the urgent problem of AIDS research. However, we need to increase and maintain the strength of both our Federally funded and privately funded research enterprises into all areas of biomedical research. The overall health of our research community contributes to our ability to solve important problems such as AIDS. Question: What is the role of the McClintock Project? [Note: The Barbara McClintock Project to Cure AIDS, proposed by ACT UP/New York, would set up a new research initiative, based at a central location outside of existing AIDS research institutions.] Martin Delaney: The meeting was not to endorse any particular proposal or project at this point. There was a representative of the McClintock Project at the meeting, and here on this panel, but right now we're identifying the problems that have to be solved. Mark Milano: Although the McClintock Project was not endorsed by the meeting, a number of concepts from the project were endorsed. The main one was finding ways to allow researchers to pursue new, innovative approaches without many of the cumbersome burdens that go along with the funding processes currently in existence. The panel itself, from an activist point of view, being composed largely of NIH researchers, tended toward fine tuning the system, rather than what ACT UP proposes in McClintock, which is somewhat removing AIDS research for a cure from the NIH and setting up a new project. Question: What scientific directions do you think represent real promise for "a prevention of AIDS" (in persons with HIV)? Martin Delaney: Our task in this meeting was not identifying exciting new scientific opportunities, but identifying where are the stumbling blocks right now. What are the pieces to which we need answers in order to move forward? Where are we stuck, and what problems need to be resolved as quickly as possible in order to move forward? The next task is to break those down into manageable pieces, get them farmed out, and get the answers done, if they're not already underway. Dr. Richard Marlink: On the first day we divided tasks into viral pathogenesis questions, and host pathogenesis questions. We have beginnings of notes which will be prepared into a document. Kristine Gebbie: One of the things I'm most impressed by was the mix of participants. We have had almost no places where the activist community, the directly affected community, the research community, and parts of the structure of how that all comes together, have met fairly comfortably in a room for an extended period of time to think together about where to go. It seemed to work here, as people moved toward consensus, and that's a model that I'm very comfortable with. I think there are lots of places in our HIV-related programs where we can apply this kind of gathering. It was exciting from the doors it might open on research, but also exciting as a test of a model that I hope I can bring to my new office. I'm glad I had a chance to be here, and I'm looking forward to the results of day three. This is a meeting that won't end. Question: What is the role of the new Office of AIDS Research in all this? Will new programs be conducted by this office, or in some way outside of or in parallel to it? Kristine Gebbie: It's a little early to say, partly because the new Office of AIDS Research is also in creation at the same time, and if it does the job that the statute outlines for it, there is some stuff I don't have to do. Clearly I'm going to pay attention to it, hopefully get invited to sit in on the next day or days of the meeting. A major part of my job, if we can get a good research coordination process within the research community, is to look at the issues around how we translate research quickly into practice, or quickly into phases of applied research, that can get us the benefits of what's known as fast as we possibly can. That's going to be a large part of what I look at, in addition to the kind of questions that have been asked here. Question: How much hope is there for treating people with full blown disease, especially at late stage? Dr. Robert Gallo: I think, realistically, in the very latest stage of AIDS, nothing new or dramatic came out at this session and won't come out of any session in the immediate future. However, there are a number of new technologies and a number of new observations that we think could move forward within this next year or two that at least make us cautiously optimistic. I feel we're in a very important transition period where we can move certain things in therapy to the clinic faster and better. In late-stage AIDS, the focus has to be on reconstitution of the immune system; there's a major effort in that direction [Project Immune Restoration, organized by Project Inform] to try to stimulate more research, it's already happening. It's almost certainly going to have to involve some aspects of transplantation research and experiment. I also have some optimism about being able to interfere with HIV replication, which is one of the most important things we have to do, not in the latest or terminal stages of AIDS, but earlier in the course of the disease. We're thinking of a number of new opportunities, like antisense, some of the experimental gene-therapy programs, and some targeting of specific or conserved regions in the HIV genome, that we hope will move forward in the coming year or so. Question: On the issue of directed or targeted research, I've heard a lot of concern from researchers, who say don't target anything, if you target you're going to spoil the whole basic-research phenomenon. What do some of the scientists think about that? Larry Kramer: Everybody agrees that we were tired of this either/or dichotomy, for every person who's for "targeted" there's a person who's not for "targeted." I think we're just going to target some things and not target others. Mark Milano: Maurice Hilleman (of Merck) talked about "filling in the ruts" in research. Investigator-initiated research often leads to the interesting questions being answered, but when it comes to the more mundane work in the trenches, many questions never get answered. Someone assigning those tasks for people to do to fill in our gaps would be crucial; there was very clear consensus on that point. Question: On prioritizing, what did you learn over the last few days that was new? Dr. Robert Gallo: I learned more details about concepts of blocking immune activation. I learned that there were derivatives of cyclosporin that supposedly can block immune activation, with all the good things that we think could come out of that, without being immunosuppressive. I do believe this would be a priority for some experimentation if true. What I learned mostly at this meeting is that a number of people are thinking in parallel ways, but there are still significant disagreements on details. Regarding your question on targeting, every time you walk into a laboratory, you make a priority decision. You do that every day in every experiment you do. Everybody targets when they do an experiment; it's just a matter of the degree, and who's going to be telling whom to do what. You don't want too much of that. One major area I'm most concerned about, that I would like to see facilitated in what people are calling a targeted program, is that when ideas and data come from basic science, they're able to go into the clinic without going down the drain because we don't know how to get them into the clinic because there's no interested manufacturer, either for patent reasons or whatever reasons there may be. That, to me, is the single most important thing we could accomplish, because there are already plenty of good ideas, and significant data in a number of areas, that are worthy of pursuit yesterday not tomorrow. Question: The question I was going to ask was just answered by Dr. Gallo, about good leads but no pharmaceutical company to develop them, or a company owns them that is only interested in cancer, say, and not AIDS. How do we get them into the first showings of activity in humans? If they pass that, they are likely to have enough momentum to be picked up. But if they don't get into humans, then as you put it they go down the drain. Could the panelists say anything else on that? Martin Delaney: It was a major topic of discussion in the meeting, because right here in the meeting were some of the basic scientists who have exciting new prospects, yet don't have the ability to turn them into a product, because they're not a company, or they're faced with creating a company in order to bring something into the clinic, which as you know is extremely difficult. I can't say we solved the problem; what we've done is gotten it on the table, targeted it for a priority development process, within what we're going to continue here, and one that wil include Dr. Kessler of the FDA, and the pharmaceutical companies, and perhaps some of the government resources. For example, the Frederick Cancer Center currently does work like that in some instances in cancer; it will take a product itself from the laboratory, and manufacture it on a small-scale basis, enough to get it into early testing and then perhaps attract a pharmaceutical sponsor. Those kinds of options are under discussion. Larry Kramer: The important thing about the meeting was the emotion and the atmosphere, and the sense of urgency, and the sense that, as Dr. Haseltine has told us, we face one billion infections shortly; that this is truly a plague, and it's time to answer to a higher God in terms of moving forward. There was a sense constantly that we have to find a way of filling in the ruts, of finding mechanisms to overcome all obstacles, of getting the research financed. This was a very broad consortium of people; had they been put together in a room a year ago, the same kind of atmosphere might not have resulted. If I heard one thing remarked over and over again, it was, "My God, why haven't we been having these kinds of meetings between the different scientists, pharmaceutical companies, etc. since day one?" In meetings like this, great amounts of information are exchanged. One has no answer for that question; it is tragic that there were no such meetings from day one. But we have started, and we feel invigorated after a time of deep depression. Question: Did you reach consensus on what a "Manhattan Project" or a special project means? Is it greater coordination? Is it smaller projects under one umbrella? Martin Delaney: When you use phrases like "Manhattan Project," you have baggage that comes with that. Some people are strongly opposed, some are strongly in favor, and it becomes a stumbling block in trying to negotiate consensus. So the consensus here was not around a Manhattan Project as a symbol, but around the substantive issues that some people would like to accomplish through that kind of a project. And those principles about coordination, use of resources, prioritization, identification of gaps, different management methods, different processes of handling research, all of that is embodied in the nine consensus statements. The next meeting will try to take that into a more specific proposal for implementing those interests. Mark Milano: As somebody who worked on authoring a Manhattan- type project, called the McClintock Project, it was clear that this meeting was not calling for that type of a project. ACT UP/New York obviously disagrees with that. But what was good to see was that these NIH researchers clearly saw a need for change in the way research is managed in this country. They were looking for ways to change research. At least ACT UP and the NIH are in agreement that things have to change, they cannot stay the way they are. At least we're moving in the direction of change. Question: Are we afraid that raising high expectations, with phrases like "Manhattan Project," might create expectations we can't live up to? Martin Delaney: We're trying to manage a delicate coalition of widely varying viewpoints. It would be presumptive to try to define today how we go about doing this. It's better for us not to be dug in on what the final solution will look like. We're working together to accomplish a joint vision, and that's why we feel so invigorated by this process. Dr. Steve Morin: Congress and the Administration are both involved in the challenge to come up with an initiative that would be more responsive to AIDS research. There have been a number of potential models floated, including the Manhattan Project, the McClintock Project, the Ariel Project on pediatric AIDS, there are six or seven. What is important about this meeting is that the supporters of each of those proposals were brought together with the scientists and with public policy makers, to try to see if some agreement could be worked out. There was a remarkable degree of consensus at this meeting. There are still points about technical detail, where total consensus may not be possible, but compromise on recommendations seems likely. Once those agreements are reached, there are structures in place, with the Office of AIDS Research and the structure of the Federal government, as well as the structures of the private organizations which fund AIDS research, to pick up these recommendations and help inform the public-policy decisions that are made through those structures. It does not require this group to carry out everything; structures are in place for organizing and funding AIDS research. Question to Gallo, Essex, and others: What compelling avenues of scientific research are now falling into what some of you have called "the ruts" -- i.e., neglected for reasons of institutional inertia? Richard Marlink: Essex and Gallo had to leave for their planes. The "ruts" were not about scientific innovation, but the opposite, "baseless science," rather than basic science, as one of the members said -- that is, not new basic science discoveries, but filling in the gaps to get a new agent or new discovery into use as quickly as possible, to see if it's going to be useful. This involves a number of different efforts that could be called science, and could be called drug development. Larry Kramer: Many of these were brought up in Jon Cohen's excellent issue of Science (May 28, 1993), on what are the unanswered questions. We want to see that the questions that everybody pretty much agrees are unanswered can get answered. Nobody has any particular new rabbit in the hat. Martin Delaney: I'll give you one example where a gap exists. There's much talk currently about immune activation as a factor in disease, and its relationship to different cytokine cascades in the immune system, and to questions of disease progression and loss of CD4. All of these are concurrent events which are associated somehow in this disease, but nobody knows which is a cause and which is an effect. Yet at this time, we don't see much research being structured to answer those kinds of questions. Until we understand that, we may be fishing about in the dark with those concepts for some time to come. We need a structured way to take that problem apart, break it down into its components, and get the job done. That's one concrete example. Question: Where was there not consensus? Mark Milano: We talked about conflicts of interest, and put that on hold until the next meeting; in biomedical research, it's a very touchy subject. And there was the debate about whether to begin a whole new project, or to fine-tune programs at the NIH. Martin Delaney: Another area is the question of R01 investigator initiated research, vs. more targeted efforts. There were heated debates about that. But as we took those debates apart, it became clear that we were partially debating our interpretations and the meanings we put behind those words. Targeted research doesn't necessarily mean dictated research. As we were able to calm down from some of the positions we all hold over those buzzwords, we were able to see that we weren't as far apart as we thought on those issues. Larry Kramer: Look upon this more like a summit meeting of people exchanging points of view and coming together for the first time, rather than a specific program. It was a very exciting summit meeting, that left us all hungry for the next meeting, and with great renewed enthusiasm after a time of great depression. Appendix: Areas of Consensus The group unanimously agreed that it is possible to develop new therapies, within a reasonable time, that are capable of providing long-term survival without clinical disease for persons infected with HIV. The following nine consensus points were also listed: 1. Insufficient resources inhibits the pace of both basic biomedical and AIDS-related research. More resources will accelerate the pace of progress. 2. Identify the gaps or discontinuities in programs of research and in the implementation of clinically relevant findings. 3. Targeted special programs should be considered for emerging, gap-filling, or risky innovative research areas. Mechanisms of prioritization are possible and will be needed. 4. Improve communication pathways and coordination among public and private investigators, e.g. develop high quality repositories for defined clinical samples. 5. The urgent challenge of AIDS highlights the problem of constituting complex drug trials using multiple proprietary compounds from distinct public and private sources. A rational and comprehensive strategy should be implemented to overcome barriers at all levels that mitigate against these novel therapeutic trials. This point addresses the crucial problem of initiating therapeutic studies with multiple, simultaneous agents. 6. The government should evaluate and institute incentives to attract the pharmaceutical industry to participate in these efforts. 7. There is a need for further development of creative thinking within the AIDS research community. This should include an assessment of different management styles and structures, and an emphasis on the training of new investigators. 8. Expand and create AIDS research programs by infusion of money and talent from outside the current NIH structure. 9. The president, his administration, and Congress must take a leadership role in educating the American public and world community on why these initiatives are important and urgent. ***** Prophylaxis: New One-Day Sulfa Desensitization Procedure by John S. James The most effective prophylactic [preventive] treatment for avoiding pneumocystis in persons with low T-helper counts is oral trimethoprim-sulfamethoxazole (TMP-SMX, best known by the brand names Septra, or Bactrim, although less expensive generic versions are available). TMP-SMX also appears to be highly effective for preventing toxoplasmosis. Unfortunately, adverse reactions to TMP-SMX occur in over half of HIV-infected patients, which often prevents use of this drug. Sometimes aerosolized pentamidine is used as an alternative, but this medication is much less effective than TMP-SMX as pneumocystis prophylaxis, and is not effective in preventing toxoplasmosis, or pneumocystis outside the lungs. It is unclear why persons with HIV have a much higher rate of reaction to TMP-SMX than those in the general population. One theory is that HIV patients have lower levels of intracellular glutathione, a substance which may help protect against toxic byproducts of the drug. There may also be a genetic predisposition to this drug reaction; certainly there seems to be a racial difference, with Black patients, both in the U. S. and other countries, being much less likely to have adverse reactions to TMP-SMX. (1) Last October, AIDS TREATMENT NEWS described an eight-day desensitization procedure reported by Marcus Conant, M. D., and his associates at the Eighth International Conference on AIDS (in Amsterdam, July 19-24, 1992). They reported successful desensitization in 21 of 25 patients with previous adverse reactions to TMP-SMX. Also, researchers at Kaiser Permanente Medical Center in Los Angeles described an alternative one-day desensitization procedure (reported by D. Gluckstein and J. Ruskin at ICAAC -- the Interscience Conference on Antimicrobial Agents and Chemotherapy -- in Anaheim, California, October 14, 1992, abstract number 1475). They reported success in 15 of 20 patients. Recently we spoke with Brian Lipson, M. D., an allergist/immunologist in Redwood City, California. He had worked with Gluckstein and Ruskin at Kaiser in developing their desensitization method, although he was not one of the authors of the ICAAC report. Recently he improved the procedure, by pretreating his patients with prednisone and antihistamines on the day before and the day of the desensitization. Antihistamines are continued for one month afterwards. Dr. Lipson has treated almost 20 patients with only one failure. That patient had not been pretreated with prednisone and antihistamine. Dr. Lipson noted that a RAST test to sulfamethoxazole may be helpful, to screen out patients at risk for anaphylactic reaction. During the desensitization, the patient has an IV access as a precaution, in case emergency treatment is needed. The TMP-SMX itself is given orally. The dose is increased every fifteen minutes, with vital signs and peak flow measured before the next dose. The entire procedure takes 12 hours, and can be done either in a hospital or in an outpatient clinic. After desensitization, patients take one DS TMP-SMX daily. Some physicians give the drug three times a week, but daily use seems less likely than intermittent use to cause a drug reaction. Some patients report redness and warmth for a few hours after each pill, but this usually subsides in a couple weeks. Dr. Lipson, working with the AIDS Community Research Consortium, has developed a protocol for a formal trial of this desensitization procedure, which he hopes to conduct in the near future. For more information, physicians and patients can contact Dr. Lipson at 415/365-6300. References 1. For background on reactions to TMP-SMX and other drugs in persons with HIV, see the review article, Drug Hypersensitivity Reactions and Human Immunodeficiency Virus Disease, by Paul J Bayard, Timothy G. Berger, and Mark A. Jacobson, JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, volume 5, number 12, 1992. ***** FDA Nutritional Supplement Regulations: Comments Due August 17 by John S. James Public comments on proposals for major changes in how the FDA regulates nutritional supplements must be received in Rockville, Maryland, by August 17. (For background information, see AIDS TREATMENT NEWS #178, July 9, 1993; for the text of the FDA proposals, see the Federal Register, Friday, June 18, 1993, pages 33690 through 33700.) To be considered, written public comments should be identified with docket number 93N-0178, and must be received by August 17 at: Dockets Management Branch (HFA-305), Food and Drug Administration, rm. 1-23, 12420 Parklawn Drive, Rockville, MD 20857. Two copies of any comments are to be submitted, except that individuals may submit one copy. Comments received are open to public inspection. These proposals are not specific rules; rather, they outline various policy options and philosophies on regulating nutritional supplements. The specifics will come in the future; at this time it is impossible to know what the real consequences will be. We are concerned that, in the rush to stop unethical marketing practices in the health-food indusry, legitimate access to unproven but rational treatment options may be lost. In over six years of publishing AIDS TREATMENT NEWS, our consistent impression has been that the best treatment strategy at this time is to try various reasonable treatment options, and keep those which seem to be working for oneself, while discarding those which seem not to work. The resulting treatment mix will be highly individual, unlikely to work for anyone else; and it will probably include treatments accepted in error, due to placebo effect, when they really have no benefit. Still, this basic strategy may be the best available today. That is why we are concerned that options may be removed without good enough reasons. Also, we have seen that pharmaceutical companies, and the rest of the mainstream system, have done very poorly in AIDS. Throughout the history of medicine, treatment improvements have often come from unexpected sources; yet mainstream research must be defensible in committees, so it is usually designed to preclude the unexpected, instead of casting a broad net for it. As a result, health-food type products such as amino acids are likely to be explored first through patients' own experimentation. From there they may come to the attention of physicians (who seldom take the lead, due to professional constraints -- including malpractice insurance, but also including the professional conservatism which, in routine medical practice, serves the public well). Only later do such substances acquire the momentum to enter formal clinical trials. But if patients cannot get them, this process may never start, and development of some treatment options could be delayed for decades. What's happening now is that the FDA is determined to assert control over large parts of the nutritional supplement industry which have not been effectively regulated. The FDA has done a very good job in explaining its position to the press and others. Meanwhile, alternative viewpoints have not been as well presented. Much of the press is accepting the FDA version as gospel, with no independent investigation. We need to make sure that the interests of people with AIDS do not get lost in the renewal of the so-called "vitamin wars" (which are less about vitamins this time than about amino acids, herbs, and miscellaneous dietary supplements). We want better regulation of safety, purity, potency, and truth in labeling. What we don't want is for patients to be unable to obtain certain treatments at all -- unless for a very good reason. Congress Hears Different Views Different views on this issue (which will continue long past the August 17 public-comment deadline) were well expressed in testimony before Congressman Henry Waxman's Subcommittee on Health and the Environment, in a hearing held on July 29, 1993. The FDA position was stated by Commissioner David A. Kessler, M. D. ; the FDA also released a 105-page report, Unsubstantiated Claims and Documented Health Hazards in the Dietary Supplment arketplace. Both documents highlight particular hazards of certain herbs (chaparral, comfrey, yohimbe, lobelia, germander, willow bark, jin bu huan, Stephania and Magnolia species, and ephedra) and other substances (L-tryptophan, phenylalanine, germanium, and overdoses of vitamin A, vitamin B6, niacin, and selenium). These lists are not exhaustive; we would like to see more warnings and precautions published by the FDA, with the public having the final choice except when the danger is great. A very different view was expressed by Fred Bingham for the Consumer Coalition for Health Choices, a new coalition of groups representing persons with AIDS and other life- threatening diseases, and other interested organizations. He is concerned that the FDA has a deep institutional bias against nutritional supplements and cannot be trusted to regulate them fairly. "The unhindered access to high-yet-safe doses of antioxidants, amino acids, herbs, and other natural products is an absolute necessity of life, if I and other PWHIVs are to continue to thrive. We cannot allow their removal, under any guise, without substantial and well- organized national protest." Another critique of FDA positions on nutritional supplements, this one highly detailed and strongly worded, was given by Jarrow L. Rogovin, president of Jarrow Formulas, Inc. He proposed "creation of nutrition Review Boards comprised of FDA, industry, academia, NIH, USDA, and consumer/patient access advocacy groups. This would ensure fairness, open up the process, and give credibility to the findings." ***** National AIDS Lobby Days, Washington, D. C., September 12-14 A coalition of AIDS organizations is sponsoring AIDSWatch Washington to meet their Congressional representatives or staff on September 13 and 14, concerning AIDS funding, research, prevention, and care. People should be in Washington on Sunday, September 12 for briefings. For more information, persons living anywhere in the U. S. can contact one of the following national organizations, which are sponsoring AIDSWatch '93: AIDS Action Council (202-986- 1300 ext. 15); American Foundation for AIDS Research; CAEAR Coalition; Human Rights Campaign Fund; Latino/a Lesbian and Gay Organization; Mobilization Against AIDS; Mothers' Voices; National Alliance of State and Territorial AIDS Directors; National Association of People with AIDS; National Hemophilia Foundation; National Native American AIDS Prevention Center; Project Inform; and Treatment Action Group. Persons in the Los Angeles area can also contact Bill Skeen, AIDS Project Los Angeles, 213/993-1347. AIDS Action Council or other organizations can assist you in making appointments with your representatives, or you can do this on your own. (Please contact AIDS Action Council by August 15 if you want them to make your appointments; when calling, indicate who your member of Congress is.) For information on special airline and hotel rates, and for reservations, call 800/728-2515; ask for Lee, Ann, or Bernadette. Note: You do not need to go to Washington to meet your Federal representatives. Congress will be in recess during August (scheduled August 9 through September 3), and this is an excellent time to meet with elected officials in your district. AIDS Action Council has a one-page "Suggestions for Meeting with a Member of Congress"; many other political organizations have similar materials. ***** In Memoriam: Larry Waites, M. D. Larry Waites, M. D., a leader in testing experimental HIV treatments and in the movement for patient empowerment, died on July 20 of congestive heart failure, due to a hereditary heart problem complicated by AIDS. Dr. Waites ran a very successful pediatric practice in San Francisco for eight years, then became interested in AIDS after the death of a close friend in 1987. While maintaining his practice, he went back to school for a masters degree in health administration, hoping to become AIDS administrator for San Francisco. He earned the degree but did not get the job. Instead he joined Alan Levin, M. D., and Vera Byers, M. D., Ph.D., in their HIV medical group, Positive Action HealthCare. Positive Action was controversial because it advocated lower AZT doses (the dose currently in use -- which they determined by measuring p24 antigen responses to treatment), and earlier AZT use (with T-helper counts above 200), long before these became standard in U. S. medical care. Especially controversial was its advertising to encourage people to get early treatment -- long before mainstream AIDS organizations did the same thing. Dr. Waites' main project at the time of his death was studies of lymphocyte transfer from healthy individuals to patients with HIV. He used this procedure with identical twins with good results, and believed it could be extended to siblings with only a partial genetic match. He did not test this with patients, however, due to delays in obtaining funding for the research. Dr. Waites carried out other immune-restoration work, including studies with PEG IL-2, a substance no longer being manufactured because of the expense (studies are testing new ways to use ordinary IL-2 instead). He also worked with another immune-system drug, THF. Dr. Waites' most controversial study was the first trial of anti-HIV use of "compound Q"; he was one of the physicians who treated patients in the 1989 "underground" study run by Project Inform, when there was much early enthusiasm for the treatment, but the mainstream trials then planned could not have given an answer quickly. Compound Q is still being tested in human trials. Dr. Waites emphasized food safety and infection-control precautions for himself and other AIDS patients. He never drank tap water anywhere, and used a dust mask when traveling by plane, or in other crowded, poorly ventilated spaces. He always bleached vegetables before making salads, never ate salads in restaurants, and insisted that restaurant meat be well done -- often sending back steaks when they were not. (For more information on food safety, nutrition, and other basic health advice, see HIV Disease Nutrition Guidelines; Practical Steps for a Healthier Life, a recent pamphlet developed by the Physicians Association of AIDS Care and underwritten by Stadtlanders Pharmacy; for a free copy, call 800/238-7828.) These and other precautions evidently worked for him, as he was able to continue his work, traveling, lecturing, etc., despite having a T-helper count around six for the last two years of his life. Dr. Waites also urged stress reduction, such as some form of meditation, and exercise, even for many patients confined at home. He encouraged patients to be educated and involved in their treatment if they wanted to, and would look into treatments they suggested that he was not familiar with. He emphasized that HIV is not an automatic death sentence, and that "the cup is half full, not half empty." A memorial service for Dr. Waites will be held at 4 p. m. Saturday August 28 at the First Unitarian Church, at Franklin and Geary Streets in San Francisco. ***** AIDS TREATMENT NEWS Published twice monthly Subscription and Editorial Office: P. O. Box 411256 San Francisco, CA 94141 800/TREAT-1-2 toll-free U. S. and Canada 415/255-0588 regular office number 415/255-4659 fax Editor and Publisher: John S. James Medical Reporters: Jason Heyman John S. James Nancy Solomon Reader Services and Business: David Keith Thom Fontaine Tadd Tobias Rae Trewartha Statement of Purpose: AIDS TREATMENT NEWS reports on experimental and standard treatments, especially those available now. We interview physicians, scientists, other health professionals, and persons with AIDS or HIV; we also collect information from meetings and conferences, medical journals, and computer databases. Long-term survivors have usually tried many different treatments, and found combinations which work for them. AIDS Treatment News does not recommend particular therapies, but seeks to increase the options available. Subscription Information: Call 800/TREAT-1-2 Businesses, Institutions, Professionals: $230/year. Nonprofit organizations: $115/year. Individuals: $100/year, or $60 for six months. Special discount for persons with financial difficulties: $45/year, or $24 for six months. If you cannot afford a subscription, please write or call. Outside North, Central, or South America, add air mail postage: $20/year, $10 for six months. Back issues available. Fax subscriptions, bulk rates, and multiple subscriptions are available; contact our office for details. Please send U. S. funds: personal check or bank draft, international postal money order, or travelers checks. VISA, Mastercard, and purchase orders also accepted. ISSN # 1052-4207 Copyright 1993 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used. &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display - - - - - - - - - - - - What I have written is my own opinion. From: Ben Gardiner Return address: ben@maggadu.Queernet.ORG -- ben@maggadu.QueerNet.ORG AIDS Info BBS 415)_626-1246 free since July 25, 1985