&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& 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 #175, May 21, 1993 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: [items are separated by "*****" for this display] Expanded Access to Experimental Drugs: Interview with David Feigal, M. D., of the FDA Long-Term Survival Gains Renewed Interest at Berlin Conference Berlin AIDS Converence Overview British AIDS Funding: Garbled Story Reaches U. S. AIDS in the World: Global Report on Epidemic Announcements: HIV, AIDS, and Chinese Medicine: San Francisco State University, June 18-20 Leading Scientists to Address Town Forum, Washington, D. C., June 2, 4:00-6:30 p. m. Correction: DaunoXome Trial Sites Include Boston ***** Expanded Access to Experimental Drugs: Interview with David Feigal, M. D., of the FDA by John S. James Editor's Note David Feigal, M. D., is Director, Division of Antiviral Drug Products of the U. S. Food and Drug Administration, in charge of approving all new antiviral drugs. AIDS TREATMENT NEWS asked for this interview for several reasons: (1) There is much discussion among patients and physicians about "when is a drug ready for parallel track." The FDA must approve any parallel track or other such access program before it can start. And (at least equally important in practice), the FDA's views will be influential in negotiations with pharmaceutical companies, which must also agree to (and usually pay for) such access to their new drugs. Understanding the FDA's approach will enable physicians, patients, and activists to direct their energies most effectively toward obtaining wider access to promising treatments. (2) The FDA wants help from the AIDS community in identifying which experimental drugs are truly promising and should be made more widely available. Physicians and patients can help in this process. (3) The FDA is prohibited from releasing proprietary information about specific drugs. This puts AIDS activists at a disadvantage in negotiating for access to treatments, because companies can blame the FDA when the real obstacle is their own reluctance; the FDA cannot defend itself, and the public finds it very difficult discover what the truth is. This problem can be minimized by documenting the fact that the FDA is more supportive of pre-approval access to experimental drugs than many people believe. Glossary A few of the terms used below will be unfamiliar to some readers. These brief explanations may help. * "The Agency." The U. S. Food and Drug Administration is informally called "the Agency" in drug-development discussions. There is no "Food and Drug Agency" -- although this phrase often appears in the press, because of reporters' confusion. * Sponsor. An organization which is developing a drug (and usually paying the large bills to do so, averaging well over $100 million in development costs for each new drug approved). Almost always the sponsor is a pharmaceutical company. But occasionally a government agency or private nonprofit organization can be a sponsor. * IND (Investigational New Drug approval). Usually an IND is permission granted by the FDA to test an experimental drug in humans. In some cases an individual physician can apply for and hold an IND. Certain special kinds of IND, such as the "treatment IND," are explained in the interview below. * Phase I, phase II, phase III. These refer to traditional phases of human trials of an experimental drug. Phase I looks for toxicity and for the maximum tolerated dose. Phase II seeks to show some indication of efficacy. Phase III compares the new drug in larger trials against existing treatments to determine its real-world usefulness. These phases are not defined or even mentioned in any law or regulation, but represent customary practices which developed over the years. Therefore the FDA has flexibility to allow new approaches. For example, in testing drugs for AIDS and other life-threatening conditions, phases I and II, or phases II and III, are sometimes combined to save time. * NDA (New Drug Application). The NDA is a voluminous document (typically dozens of boxes of paper) submitted by a sponsor to the FDA to apply for approval to market a new drug. * Accelerated Approval. This is a new system by which the FDA can grant full approval to an urgently needed new drug based largely on "surrogate marker" endpoints (such as blood tests), instead of waiting for proof of long-term clinical benefit -- provided that the company agrees to do the additional research (to prove clinical benefit) after approval. The only AIDS example of accelerated approval so far is the drug ddC; ddI was approved in a similar fashion, only before the accelerated-approval regulations were written. * Expanded access. "Expanded access" is a generic term which applies to a number of different programs to allow patients to use an experimental drug before it receives final marketing approval. * Parallel track. This is the most recent expanded-access program. The only official parallel-track program so far is for the drug d4T. The major pre-approval access program for ddI was in fact parallel track (but not officially so, since the parallel-track regulations had not been written at that time). Interview with David Feigal, M. D., May 5, 1993 JJ: During an earlier conference call [on March 15], FDA Commissioner David Kessler strongly supported parallel track as a way to make important treatments available, so that patients do not need to resort to underground treatments and use drugs without quality control. DF: Let me put parallel track in the context of the different procedures which are available and have been used. It is part of an overall commitment by the Agency to make drugs available early to patients with life-threatening diseases. Parallel track is based on the premise that if the drugs are far enough along to test them in large-scale trials, then it is also reasonable to make the drugs available to the patients who cannot get into those trials -- particularly if they have no other alternative. If you look at the different regulatory mechanisms for this purpose, one of the oldest is the "emergency IND," sometimes called "compassionate use." We avoid the word "compassionate" because during testing you don't know if the drug works or not, so it is hard to tell if you are being compassionate or not, depending on whether the drug is any good. Emergency INDs are essentially single-patient protocols, where the sponsor has to be willing to provide the drug, and the physician has to be willing to take responsibility for describing the patient and how the drug was used, and giving us some follow-up. These programs have had as many as 300 or 400 patients per year enrolled in them; some of the drugs have been used for HIV, usually for opportunistic infections. These are particularly useful when a sponsor is not pursuing or is barely pursuing licensure for a drug, perhaps because the market in this country is too small; yet the drug is available because it is approved somewhere else in the world, and the company is willing to supply it. Sometimes these programs have been coordinated by the Centers for Disease Control, and they take on some of the sponsor's responsibility. For example, they are now providing streptomycin and will soon be providing PAS [both old drugs for tuberculosis, needed now because of resistance to the standard drugs]. Their largest program in AIDS was when they were the sole provider in the country for pentamidine, for injection use for treating pneumocystis. The next kind of program under a traditional IND that companies can sponsor is what we call "large safety trials." These are not controlled trials; everybody gets drug. They only differ from emergency INDs in that the sponsor takes responsibility for the reporting and tracking of patients, rather than individual physicians one-by-one as with an emergency IND. Some of the safety data used for AIDS drug approvals have been done under this mechanism of the large open safety trial. Some of the early use of ddI, for example, used this method. Historically, the next kind of availability that came along was, for cancer, the "class C" drugs, and for non-cancer, the "treatment IND." The treatment IND usually is used when a drug is substantially complete in getting its phase III trials done; typically it is filed about when an NDA is filed, or while an NDA is being prepared, so that in the six months it may take the company to prepare an NDA, and the six months it takes us to review it, the drug can be available to patients. Also, the treatment IND can be used earlier. For example, the ddI expanded access program technically was a treatment IND. But there are certain things in the treatment IND language [in Federal regulations] that limit its use. For example, there has to be no satisfactory alternative; and the manufacturer has to be pursuing marketing approval with due diligence. "No satisfactory alternative" creates a difficulty in certain conditions, for example with early treatment, or combination use. If there is no consensus that those are proved indications, the lack of satisfactory alternatives doesn't ring true. So for earliest use, when you don't know where the drug fits in, parallel track can be helpful. Parallel track has some features that are unique. One is that it specifies in the regulations that the Parallel Track only applies to AIDS, whereas all the other mechanisms are available for all life- threatening diseases. Parallel track was based on the idea of an access program that would run in parallel to the phase II or phase III trials, more typically the phase III trials. It is for patients who geographically could not get into those trials, or who did not meet some of the entry criteria. The only real parallel track so far has been d4T. But the large programs done with ddI and ddC were in spirit parallel track. Since the parallel track rules hadn't been written yet, we borrowed other regulations. JJ: Does "schedule C" [a program for cancer drugs] work differently? There seem to be many more drugs to test with a few patients, as part of serious trials. DF: There are different mechanisms in cancer, partly because of the way the programs have been set up. For example, the National Cancer Institute (NCI) has a library of different drugs that have been screened in tissue-culture systems. An individual investigator who wants to get one of those drugs files a letter of intent with the Investigational Drug Branch of the NCI, and they can work out a protocol where they treat their own patients, maybe one, maybe a small study of a group of patients. What is different is that the NCI has a mass screening from big chemical libraries. They have candidate drugs that have gone through laboratory screening and some animal toxicology. For drugs that belong to a commercial sponsor, they have a standard way of setting up the business arrangements between the government, the sponsor, and the investigator. Historically, if you look back at what many people envisioned for the ACTG [AIDS Clinical Trials Group of the U. S. National Institute of Allergy and Infectious Diseases], they thought that might be how the ACTG would be set up. But AZT changed the environment to doing active-control, larger trials, instead of having a network of physicians who would screen dozens or hundreds of candidate drugs. It is a challenge to find the best way to do the initial human studies; I think it's a mixture of science, good intentions, and historical accident that we have the system we do today. JJ: How do we get around the existing obstacles in the AIDS drug-development system? When there is a good rationale for a treatment based on evidence, there may be no way physicians and patients can choose the drug. Parallel track, etc., all require that a sponsor be willing to participate. What incentive do sponsors have to accept the cost, and possible liability exposure, for no direct financial benefit? DF: Let me comment from the FDA perspective first, about what we consider a good candidate. What are the kinds of drugs that prompt us to call the company and say you ought to be thinking of some kind of expanded-access program? One, there has to be some evidence of promise that the drug will be effective. And almost more important at the early stage, is that we need to know enough to be confident that it will be safe. One of the assumptions we make with the expanded-access mechanisms is that the drugs are going to be more loosely supervised than they will be in clinical trials. Because of that loose supervision we need to be sure that it's not toxic to the liver, lymphocytes, etc., and would do more damage than good. The evidence for effectiveness requires a case by case decision. If the drug is in a class where we already have approved drugs, there has to be more of a case for expanded access than for a drug in an entirely new class [which might have unique value]. Now we have a number of drugs in new classes, such as tat inhibitors, protease inhibitors, and non-nucleoside reverse transcriptase inhibitors, that are coming along in testing. None of them have gone far enough to show the kind of effectiveness that we would feel strongly for pushing for early access. We're beginning to get data in. We hope that something in these classes will be promising. But the data cannot just be laboratory work with cell cultures, it cannot just be animal effectiveness; there must be other evidence, usually from clinical trial. For example, when the ddI access program started there was data on about 100 patients. It takes some evidence of effectiveness, and it has to meet some need; there has to be some public-health need for expanded access. For example, with pneumocystis treatment, trimethoprim- sulfa is good enough that there's no reason to have an expanded access for a first-line drug for pneumocystis. But, given the allergic reactions with available drugs, and given the fact that severe cases of pneumocystis are difficult to treat, it would be fairly easy to make a public-health case for expanded access to a new drug for treatment failures. It goes case by case, depending on the disease, and depending on what other drugs are available and what their strengths and weaknesses are. You asked about commercial disincentives. With a couple exceptions, most of the expanded access that has taken place has been initiated by industry. There are companies that expressed an interest very early. And note that the company that sponsored the largest and probably most expensive expanded access, ddI, came back for more when they developed d4T and wanted to do a parallel-track program. Why companies do expanded access is a question you could best ask them. For the large companies, there are a number of advantages to the program -- in learning about the safety of their drug, and in getting visibility for a drug (especially important in a crowded market). I think the main incentive for them is that it cements in the public's eye that this is an up- and-coming drug, one valuable enough that it's being made available early. That kind of market influence is hard to come by in other ways. The decision is probably a combination of business interest, the chance to learn about the drug that way, and in some cases a strong element of public service. Companies can recover expenses of expanded access programs by charging patients for drugs before they are approved, if they have the FDA's permission. But this very seldom happens. Companies fear that the documentation they would have to produce to justify the price would reveal more about their business practices than they wish to have known, since currently that material is private and not reviewed by anybody. And many of these drugs have a long development process; it's hard to tell early how large a market they will have. So companies may be concerned about setting a price for expanded access, as it may not reflect the price they eventually want to charge when they get to the marketplace. Except for pricing of an experimental drug, the FDA currently has no jurisdiction on pricing. Under the current law it's none of our business. My guess is that the companies enjoy that lack of supervision and don't want to get it started in any area. The economic disincentives of expanded access are definitely a concern for the small companies. They have economic problems everywhere they turn; drug development is an expensive business, requiring animal testing, clinical trials, etc. This is one more area where a small company will say they cannot afford a program. The tougher position is sometimes for the bigger companies that overall are large companies, but may look at some product areas as though they were small companies. If they don't see them as having large markets, they may not put much resources behind them. Sometimes there are resource decisions not to pursue expanded access. I and others have speculated that one reason some companies do early drug testing in Europe and not the United States is to avoid the pressure to have expanded access after the first couple of trials are approved. In Europe they can see if the drugs work or not, without having to worry about expanded access. If these trials are successful the company can begin their development in the United States, and live with an expanded access as part of the cost of that. There are other reasons companies do trials in Europe instead of the U. S. Many are European companies; they have public-relations problems when they don't start their studies in their own countries. Another reason is that it is easiest to evaluate a new drug effect in patients who have never taken an antiviral drug before. Because AZT is not used in early disease in Europe, and ddI still is not approved in the United Kingdom and many other European countries, it is easier to find drug- naive patients in Europe. JJ: When a small company has developed something, and for whatever reason it has not been sold to a big company, are we out of luck? The case of peptide T is on peoples' minds. What can we do for the future? We don't see any solution in such a case. DF: It is tough. Small companies have trouble even getting past the 100-patient trials. As soon as they get into the several-hundred-patient trials with longer-term follow-up, or with complete viral or immunological monitoring, they may not have enough money to proceed. They are stuck at that point with having to find a business partner. They might be able to try it with the ACTG; there are drugs from small sponsors that have had some testing there. They need to find a source of backing, and traditionally it is a partnership with a larger, old-style company. That is a problem for them whether or not there is parallel track. One proposal has been to require more early animal testing for reproductive toxicology, so we can make early access to drugs a reality for pregnant women. If we took the cost of those studies to the small companies before they had even screened the drugs in phase I/II for efficacy, that would discourage the development of some compounds as well. It's a rock and a hard place, some of the issues you get caught between in drug development. What about interference with drug development by these expanded access programs? The answer has been mixed. With AZT, there was no effect, since the treatment IND was a bridging maneuver during review and before full marketing. It did not compete with any trial, and it provided drug to three or four thousand patients half a year earlier than they otherwise would have received it. With ddI, the ACTG does not think that early access interfered with recruiting for the trials. Concern about pancreatitis had a chilling effect for several months. But recruitment was nevertheless very close to what had been targeted. ddC did get clobbered, but not by its own expanded access, but by ddI. ddI was the drug that everyone wanted to get on, and it sort of shut everything else down. If there had not been ddI expanded access, maybe the ddC clinical trials would have accrued more rapidly, but only to the extent that patients on expanded access would have gone to ACTG centers and signed up. With drugs for opportunistic infections, most of the expanded access has been after the trials were finished, with the exception of atovaquone (Mepron). There was a fair amount of atovaquone availability while trials were still going on. I don't see any evidence that expanded access for atovaquone interfered with recruitment for its clinical trials. There was a lot of enthusiasm for that drug during its testing, and both the clinical trials and the expanded access accrued fairly well. Clarithromycin had an expanded-access program during its trials, but the sponsor did not have trouble conducting the studies which are now being presented (to the FDA's advisory committee). The concern is a real one. It would be possible to set up widespread use of drugs through expanded access or accelerated approval that would have a discouraging effect on further studies. Accelerated approval may be a much bigger threat than parallel track for dampening enthusiasm for clinical trials. I'm concerned at the difficulty there has been in launching combination trials of ddC. Once a drug gets accelerated approval, that makes its use so widespread that it is hard to find participants who are interested, and investigators may want to move on to new drugs. Unapproved drugs somehow seem more attractive than approved drugs. JJ: From here it looks like the problem is getting companies motivated to do the trials when there has been accelerated approval. DF: We hope that the initiative in industry to be more cooperative in combination trials will break down some of the barriers. It often takes the companies a very long time to decide whether to do studies with their competitors, even when the trial provides no way for them to lose, since with combinations, the patients will be taking both drugs. ***** Long-Term Survival Gains Renewed Interest at Berlin Conference by Dave Gilden Even without a cure, a certain number of individuals remain healthy for a decade or more after infection with HIV. Some have normal T-helper counts while others may survive even with drastically reduced T-helper cell counts. The individual variation in response to HIV is a promising field to research. Studying the reasons for successful immune response to HIV could lead to new therapies for people with HIV whose health is declining. This June's International Conference on AIDS [see Conference overview, below] will focus new attention on the factors that make for long-term survival. The four panels the Conference is organizing on the subject will discuss it on a variety of levels, from the molecular influences to the social ones. Reflecting the International Conferences' habitual tone, the most prominently scheduled of the four panels examines the biochemistry of long- term resistance to HIV. The session's chairman, Jay Levy, M. D., of the University of California San Francisco, is one investigator who has been following a group of long-term survivors since the mid-eighties. He gave a lecture in San Francisco on April 28 that previewed his Berlin presentation. One aspect of Levy's work concentrates on the immune system's ability to control HIV after the initial acute infection. He thinks that the crucial immune system constituent is a particular type of cell called the cytotoxic lymphocyte. Cytotoxic lymphocytes are white blood cells that usually search out and kill virus-infected cells. The subgroup that interests Dr. Levy instead secretes a chemical (a "cytokine") that suppresses HIV replication within infected cells. A decrease in the effectiveness of these lymphocytes allows HIV to escape immune surveillance, and as HIV replicates, a virulent, AIDS- triggering strain eventually evolves. Levy has been trying to identify the unknown cytokine since 1986 in the hope of using it as a treatment. He thinks he may finally be able to reveal its nature in Berlin. Another panel will examine "markers of nonprogression of disease." A number of researchers are studying long-term survivors as part of "natural history" studies that trace the progress of HIV infection. Susan Buchbinder, M. D., of San Francisco Department of Public Health AIDS Office will chair this workshop. She also coordinates the San Francisco City Clinic Cohort. Now used for following the AIDS epidemic, this cohort goes back to the late seventies, when its members were recruited for a hepatitis B vaccine trial. It contains some of the longest known survivors of HIV. Dr. Buchbinder reports that her study has been a fertile source of blood specimens for researchers who are looking at individual genetic differences, immune cell activity and viral strain characteristics for leads as to what predicts nonprogression. One of the presenters in this workshop is Haynes Sheppard, Ph.D. He commented, "We all hoped that there would be definite signs, but there seem to be multiple types of nonprogression. A number of different things can protect you: good immune response, nonaggressive virus, or low immune activation. When all are bad, that's when you get rapid progression." The cellular aspects of disease resistance covered in these two sessions are not necessarily of direct interest for people with HIV. Aldyn McKean, a long-term survivor and member of ACT UP/New York, told AIDS TREATMENT NEWS, "I am much more interested in the things I can control myself than finding out that the reason I'm alive is because of a certain genetic makeup or a less virulent virus." McKean is co-chairing a roundtable discussion on the psychosocial elements involved in long-term survival. Most long-term survivors recommend specific practices that seem to help them. The measures are quite diverse and include nutrition, avoiding alcohol and tobacco, exercise, stress management and other types of coping skills, active social and sex life, a good working relationship with a doctor, and careful preventive measures against infection with other diseases. The panel's purpose is to examine what can be applied from survivors' experience to the care and support of people with HIV or AIDS. Three of the speakers will be long-term survivors, another is a clinical psychologist, and two are physicians from developing countries. The multicultural perspective that the non-U. S. residents bring to the subject of survival will contribute fresh insights as to how different environments and types of care influence survival. The fourth session will further enable conference attendees to apply the lessons of long-term survival to their daily lives. Participants from the first three panels will join together in a "meet the experts" event that will discuss questions raised by the audience. "I have a sense that people will be interested in how long-term survival differs across regions, how access to care affects survival, the effect of pregnancy, and what personal suggestions individuals have," said Nancy Hessol, who is chairing this fourth event. Comment Activists at last year's International Conference on AIDS in Amsterdam denounced the lack of emphasis on long-term survival research. They called for more concentration on long-term survival this year at the conference in Berlin. Aldyn McKean and others from ACT UP/New York and ACT UP/Europe negotiated extensively with the organizers of this year's conference. McKean wants the Berlin Conference to be a prelude to more intensive study of long-term survival. He said, "So far, small studies have occurred within already established cohorts, but no one has ever put together a large enough group to analyze variable combinations of multiple factors related to survival. I would like to see thorough interviews of thousands of people." The idea of studying what makes people healthy as well as what makes them sick might seem logical to some. But, in fact, last year was a frustrating one for studying successful resistance to HIV. The federal government shifted money that previously supported studies on the course of HIV infection to surveys designed to test the feasibility of large-scale vaccine trials. The San Francisco Men's Health Study, a source of data and funds for Drs. Levy and Sheppard's research, was canceled completely, and work on the San Francisco City Clinic cohort was curtailed. At the same time, the immediate needs of people with HIV has created pressure in the opposite direction. Susan Buchbinder reports that her group's historic series of blood samples has attracted collaborators from other institutions. These researchers have succeeded in finding funding for investigating signs of nonprogression. And discussions are continuing with the National Institutes of Health (NIH) to save at least some portion of the San Francisco Men's Health Study, including the follow-up on long-term survivors. NIH scientists are also talking about setting up a national registry of long-term survivors, according to McKean and Buchbinder. This would be a first step to the comprehensive surveys that McKean envisions. [Note: Dave Gilden plans to attend the Berlin meetings on long-term survivors and review them for AIDS TREATMENT NEWS.] ***** Berlin Conference Overview by John S. James The major scientific AIDS conference of 1993, the IXth International Conference on AIDS/IVth STD World Congress, will take place June 7-11 at the International Congress Center in Berlin. A number of satellite meetings, organized by nonprofit groups, pharmaceutical companies, and others, are also scheduled at the time of the conference and during the days immediately before and after. No one expects breakthroughs at these annual conferences, but we do expect significant advances in a number of fields. It is hard to know ahead of time what will be presented at the international conference -- which is unfortunate, because upon registration one receives two thousand pages or more of poorly indexed material, and there is not enough time then to scan it to discover relevant projects and persons one should meet, without missing ongoing events. Most of what can be learned in advance comes through the rumor mill. Some of the following are not confirmed; the list below includes predictions we have heard which seem plausible. We have no way of knowing what will be most important at the conference. Here are some of the areas we will be watching. * Combination antivirals. Some results of ACTG 155 (AZT plus ddC combination, compared to each of the drugs alone) are expected. This large, well-designed study could affect clinical practice, depending on the results. We have no information on what the results will be. Naturally we will be listening for talk about "convergent combination" antivirals (see AIDS TREATMENT NEWS #170, March 5, 1993). But there is very little human experience with this treatment approach at this time, so no definitive information will be available. * Protease inhibitors. This class of antiviral has long worked well in the laboratory, and been of great interest to scientists. The challenge has been making these chemicals work as drugs -- be nontoxic, water soluble, able to get to where they are needed in the body, etc. Several pharmaceutical companies are developing protease inhibitors, but only one, Hoffmann-La Roche Inc., has done extensive human testing, in Europe. It's drug is believed to be safe, but even drug experts outside the company have no idea how well it may be working. It is rumored that Roche will present at least a little information about this drug in Berlin. * Tat inhibitor. Only one company has a tat inhibitor in human trials -- Hoffmann-La Roche again. This drug is being tested in the U. S., and some information on antiviral activity in humans may be released in June, after stored blood samples are tested in a batch. Meanwhile, anecdotal reports are generally mediocre; there has been no groundswell of enthusiasm for this drug among people in the trial. Tat inhibitors still remain one of the most promising treatment possibilities. Anyone can develop them, because the technology to do so is in the public domain. But other companies seem to have held back their efforts to wait and see how the Roche drug does. If it succeeds, others are likely to jump in with tat-inhibitor products; if Roche strikes out with this particular chemical, other companies are likely to flock the other way and abandon the area. The public interest would be better served by developing alternatives now, in case the Roche drug fails for reasons specific to that particular compound, which would not apply to other tat drugs. There are rumors that some information about the Roche tat inhibitor may be released at the Berlin conference. * AZT, Concorde study. We will be watching for more information about the controversial Concorde study, which reported no benefit from early use of AZT in asymptomatic patients, compared to starting AZT later (see AIDS TREATMENT NEWS #173, April 23, 1993). This study has had little effect on medical practice so far, partly because very little information has been released. We do not know if a more complete analysis will be ready in time for the Berlin meeting. * Viral assays. More accurate and practical ways of measuring viral activity or viral load in people would greatly speed the discovery of better drugs and combinations. We will be looking especially for information on quantitative PCR, on branched DNA signal amplification for measuring HIV RNA, and on the p24 antigen test. The latter is inexpensive and readily available, has been improved in recent years, and is still widely used in drug development, so it can serve as a stopgap until the more sophisticated tests become more accessible to smaller, community-based organizations. * Immunological assays. Here the technical problem has been understanding the pathogenesis of HIV disease well enough to know what immunological measurements are important. The practical problem has been getting funding to develop these assays, since U. S. government support for AIDS research has been reduced, and corporate research seldom has much interest beyond the approval of the next product. * Pathogenesis [how a disease develops]. Anthony Fauci, M. D., may present a unified theory of HIV pathogenesis, an attempt to integrate what is known from the work of many scientific teams. * Science overview. The well-known AIDS scientists around the world are usually located at a crossroads of science, in contact with leading scientists everywhere. We will be listening both for overview or summary talks, and also for any new results from their own laboratories. * Alternative and traditional treatments. Here the problem is getting funding to do research to get publicly-verifiable data. There are sessions on alternative treatments at the conference, especially workshop B 29, "Natural and Traditional Medicine," scheduled for June 11 at 8:30, and a round table discussion, "Risks and Benefits of Contemporary Natural and Biomedical Treatment," June 9 at 11:15 (note: schedules may change). Three satellite workshops are planned: Early Intervention Strategies in HIV and AIDS (which will look particularly at antioxidants), chaired by H. D. Wolfstaedter, F. R., and scheduled for June 7 at 20:00, at Westend Hospital in Berlin; designing Clinical Trials with NATC [Natural, Alternative, Traditional, and Complementary] Therapies, chaired by Prof. Dr. H. J. Shroff, scheduled for June 11 at 20.00, at Westend Hospital; and Evaluation of Case Studies at the Community Level, chaired by Kaiya Montaocean, Ph.D., June 8 at 11:00, in room 10 of the conference center. A fourth satellite workshop, Psychoneuroimmunology in AIDS, had to be canceled because there was no funding to bring the speakers to Berlin. Check times and locations because they may change. During the conference, you can call Wolfstaedter's phone, 453-9328 (in Berlin), for a taped message with current information. On June 12th, the day after the conference, there will be a meeting of the Natural Alternative Traditional and Complementary Medicines Caucus of the International AIDS Society; check the number above for time and place. Also, AIDS TREATMENT NEWS will share a booth during the conference with Kaiya Montaocean's organization, the Center for Natural and Traditional Medicines, in Washington, D. C. ; the booth is #12-133. * Nutrition. Despite universal agreement that nutrition is important, the problem, again, is getting it taken seriously, since unlike pharmaceutical drugs, this field seldom moves lots of money around. Last year's International Conference on AIDS had more nutrition information than those before. We hope this increasing emphasis will continue. * Other treatments. We will also be watching for new information on many other drugs and treatment approaches not in the categories above. * Changing standards of care. The most immediately important information from the international conferences is that which affects physicians' practical treatment decisions in the near future. This information needs to be evaluated by specialists in each medical field, and it may be some time after the conference before professional consensus develops. * International communication. (1) In many fields of science, leading work is done using computer communication to allow scientists around the world to work together. (See "Doing Science on the Network," The New York Times, May 18, 1993, "Science Times" section; often, for example, new work appears first on bulletin boards on the Internet, well before it is printed in journals.) AIDS has been behind other fields in using this technology internationally, but some projects are in operation. Cost is not the main issue, as computer communication is usually less expensive than other kinds. (2) Two Global Meetings on AIDS issues are scheduled in the conference program for Sunday at 20:00 (8 p. m.) and Friday at 14:00. Last year, these meetings served as a forum to express different issues, but it was difficult to organize long- range, ongoing projects with people from very different backgrounds who had not communicated before. (3) "Community-Based AIDS Prevention and Care in Africa: Building on Local Initiatives," is scheduled for June 5 at 14:00 at The Hotel Penta. This meeting is funded by The Wellcome Foundation, Ltd.; we have not seen it listed in conference schedules. There may be many meetings like this which can be hard to find if they are not listed in a central place. * Activist meeting. The first activist meeting at the Conference, organized by ACT UP/New York for activists from around the world, is scheduled for Saturday, June 5th, at 19:00 (7:00 p. m.) at Asta Buro, at the Technical University on Strasse des Juni 17, (off Ernst Reuter Platz, one subway stop from the central station) behind the architecture building. This will be a meeting place for the whole week. * The unexpected. It is always possible that the most important advances are ones we do not know about, or do not recognize at first. ***** Berlin Conference -- Preliminary Checklist by John S. James Note: We received this information after the articles above had gone to press. Each year's International Conference on AIDS is divided into four tracks: Basic Science (track A), Clinical Science and Care (track B), Epidemiology and Prevention (track C), and Psychological and Social Impact, and Social Response (track D). AIDS TREATMENT NEWS focuses mostly on track B and track A. We have seen a preliminary schedule for track B, listing presenters and titles only (not the abstracts of the presentations, which will be available at the conference site). We have not seen a schedule for track A. The list below, together with "Berlin AIDS Conference Overview" in our last issue (#175), is the beginning of our checklist of some of the interesting presentations that we intend to cover at the conference. Note that only those of track B are listed by date (the Sunday, June 7 round table is not in any track, since it takes place before the official opening of the conference). The track A presentations are listed as "date unknown," since we have not seen the schedule; in fact, we have not seen their authors or titles either, but are trusting the judgment of one of the conference organizers who suggested these to us. We expect to add many more track A reports to our checklist when we see the track A schedule and abstracts. Each workshop session consists of six related presentations. Workshops are listed in the format "B03 #5" -- where "B" is the track, "03" is the workshop number, and "5" is the presentation (1-6) within workshop B03. Besides workshops, there are plenaries and other kinds of sessions, which are not listed here. Every year, lack of prior access to schedules and abstracts has been a problem with these conferences. Many other conferences do send out abstracts in advance. For a conference this large, the information should be available in computer form. Better communication must be planned; for example, when abstract submission forms are printed, they might need to give notice that accepted abstracts would be distributed before the meeting. We do not know if there is still time to make this change for the 1994 conference in Tokyo. And with different people managing each conference, there is not enough continuity of working relationships to build the momentum needed to make such a change. It may be better, instead, to focus efforts on computer-based international scientific collaboration, with physical conferences used to supplement computer communication when face-to-face interaction is needed. The information below is preliminary, as schedules may change. This listing (in this and our previous issue) represents only a fraction of the research reports likely to be regarded as most important after the Berlin conference. Sunday, June 7 * The Concorde early-AZT study will be discussed at a round table on Sunday June 6, 8:30 a.m. to 11:00; other topics, including tuberculosis, will be discussed after 11:00 a.m. This meeting is open, and there is no admission; but you must have already registered for the International Conference itself, in order to get through the security. This round table is organized by Tom Merigan, M. D., of Stanford. It will take place in Halle 10.2/Fairground, at the International Congress Center site. Other presentations and discussions of the Concorde results will occur later in the conference. Date Unknown A21: #2 anti-idiotypic antibodies A22: #4 immunogenicity of vaccines A07: #3 resistance to infection A19: #1 resistance against protease inhibitors; #5 L661 plus AZT A20: gene therapy Monday June 7 B01: #1 "SI" virus; #3 survival; #5 treated natural history, markers. Tuesday June 8 B08: #6 sinusitis. Also note: The Global Network of People Living with HIV/AIDS will meet Tuesday, June 8, 14.00-16.00 hrs, in Room 9 of the Conference Center. "Here's your chance to tell the IXth International Conference on AIDS about access to treatment and treatment information in your community. This is an opportunity for people living with HIV/AIDS to speak for themselves. You'll do the talking and the doctors, government officials, AIDS service organizations and media will do the listening." Participants are asked to sign up by 17.00 hrs Monday June 7, at the booth of the Global Network of People Living with HIV/AIDS, or AIDS TREATMENT NEWS (booth #12-133). Wednesday June 9 B13: #5 letrazuril; #6 paromomycin. B02: #2 markers; #6T-cell functional assay. B36: #6 "Alpha" trial. B03: Survival (technical) B28: #1 and #2 Salk HIV Immunogen; #6 identical twins lymphocyte transfer. B05: #5 new ICD p24. Thursday June 10 B15: #2 CD8 expansion; #3 daunorubicin; #6 doxorubicin. B11: #2 MSL 109; #5 HPMPC. B24: #1 ddI; #3 "Alpha" trial; #4 ddI/ddC; #5 Concorde; #6 AZT. B25: #1 ACTG 155; #2 and #3 resistance; #5 convergent combination therapy; #6 ddI+AZT vs. ddC+AZT. B32: #6, Herbal. B26: #1 Nevirapine; #2 3TC; #3 protease (Roche); #4 L661+AZT, Frankfurt study; #5 tat; #6 protease (Abbott). Friday June 11 B29: Natural and traditional therapies. #1 oriental treatments; #2 medical acupuncture; #3 compound ELS, Tanzania; #4 compound Q, San Francisco General Hospital; #5 exercise; #6 survey. ***** British AIDS Funding: Garbled Story Reaches U. S. by John S. James Rumors are circulating in the U. S. about enormous AIDS funding cuts in the UK; there has even been talk about people changing their airline tickets to demonstrate in London on the way back from the International Conference in Berlin. A fear has been that British cuts could spread to the U. S. and begin a worldwide retrenchment and abandonment of AIDS. In fact, the cuts are far less drastic than some have believed. The news is complex -- and not all of it is bad. Edward King, a well-known AIDS writer and activist in the UK, explained to us that two different events have been confused: (1) A new policy has imposed a limit of #150,000 per year in "Section 64" government funding to a voluntary organization. This is serious for the Terrence Higgins Trust, the largest AIDS service organization in the UK, which will see its government support decrease from #450,000 to #150,000 over the next three years. Fortunately, this group also receives money from other sources, for example $1,700,000 from the rock group Queen in April 1992. There are only three voluntary organizations in the country which get enough Section 64 money to be affected by the #150,000 limit; the other two are London Lighthouse, which provides medical care, and ACET, a Christian AIDS education organization. Meanwhile, funding for the state-run AIDS programs continues to increase. The usual source of funding, competing for contracts from units of the National Health Service, is not affected by the new limit. (2) In a largely unrelated policy change, AIDS education programs in the UK will move away from warning everyone to practice safer sex, and target this message to those at highest risk, for example gay men. This change happened because the epidemic has not broken out into the general heterosexual population in the UK, as it had been expected to do. Activists there have long pushed for better targeting of these campaigns, as most organizations which did AIDS prevention education did nothing directed toward gay men -- and few of those who did produced credible material. More information can be found in "Paying for AIDS," by Simon Watney, Gay Times, May 1993, and in articles in Pink Paper by David Bridle, May 9, and by Edward King, in press for May 16. King told AIDS TREATMENT NEWS, "Although I do think that the cuts in Section 64 funding are bad news, I'm surprised that people would go so far as to rearrange their travel plans to come to London to protest them. I certainly don't think they should protest the announcement about education priorities." ***** AIDS in the World: Global Report on Epidemic The Global AIDS Policy Coalition at Harvard University has published AIDS in the World, A Global Report, a 1038-page examination of AIDS from a global perspective. Edited by Jonathan Mann, Daniel J. M. Tarantola, and Thomas W. Netter, each section is written by an expert in that field, offering different, well-informed perspectives. The section on treatments for HIV and AIDS was compiled with help from AIDS TREATMENT NEWS, and offers a review of research achievements, treatment politics, and an index of available treatments, both pharmaceutical and alternative. The book also emphasizes human rights, and the effects of AIDS on developing countries. For example, one section calculated the cost of AZT around the world in terms of per capita gross national product -- from 14 percent in the U. S. to 500 percent in Rwanda, Uganda, and many other countries. AIDS in the World projects that up to 108 million people will be infected with HIV by the year 2000. This figure is controversial because the World Health Organization (WHO) predicts between 30 and 40 million. The difference is important because it affects the allocation of resources to HIV services. The Harvard group used the Delphi method, "a technique for reaching expert consensus on estimates for which no correct answer can be ascertained." The Delphi method is based on written estimates from experts who do not know the identities of the other experts involved. The WHO estimates were presumably based more closely on officially reported figures. The book costs $22.95 paperback, $45.00 hard cover, and can be ordered from Harvard University Press, phone 617/495-2577, or fax 617/495-8924. Outside of the United States call their London office at 44-71-404-0712, or fax 44-71-404-0601. ***** Announcements ** HIV, AIDS, and Chinese Medicine Conference: San Francisco State University, June 18-20 "HIV, AIDS, and Chinese Medicine: A first international conference to explore the role of traditional Chinese medicine (TCM) in the treatment of HIV and AIDS" will be held from Friday evening, June 20, through that Sunday afternoon. It is sponsored by the Institute of Holistic Healing Studies at San Francisco State University, and the Chinese Medical Sciences Research Institute, San Francisco. There are 14 co- sponsors; those most likely to be familiar to our readers are Project Inform, Quan Yin Healing Arts Center, and the Immune Enhancement Program, all located in San Francisco, and the Institute for Traditional Medicine, in Portland, Oregon. The conference fee is $145; dormitory rooms and meals are available for as little as $75 for the two days (shared room in a residence hall). For a copy of the program, which includes a list of presenters, call 415/453-2130. ** Leading Scientists to Address Town Forum, Washington, D. C., June 2, 4:00-6:30 p. m. Five leading AIDS experts, Anthony S. Fauci, M. D., Robert C. Gallo, M. D., Enrico Garaci, M. D., Michael S. Gottleib, M. D., and Robert R. Redfield, M. D., are scheduled to speak at "A Town Forum on AIDS," on Wednesday, June 2, from 4:00 to 6:30 p.m. at George Washington University's Lisner Auditorium, 730 21st St. NW, in Washington, D. C. The meeting is convened by Allan L. Goldstein, Ph.D., Professor and Chair of the Department of Biochemistry and Molecular Biology of George Washington University, and scientific director of the Institute for Advanced Studies in Immunology and Aging; it will be moderated by Carole Simpson of ABC News. For more information, call Alixe McNeill at 202/333-8845. ** Correction: DaunoXome Trial Sites Include Boston A clinical trial of liposomal daunorubicin (brand name DaunoXome) for treating Kaposi's sarcoma (KS) is being conducted at ten cities across the U. S. AIDS TREATMENT NEWS #174 (May 7, 1993) listed those cities, but erroneously omitted Boston. The correct list is: Boston, Chicago, Houston, Los Angeles, New York, Palm Springs, Portland, San Francisco, Tucson, and Washington. In addition, there is a compassionate-use protocol of DaunoXome for certain patients with advanced KS who do not qualify for the trial. It is available in Boston, Los Angeles, New York, and San Francisco. This list was correct in issue #174. For more information about either the trial or the compassionate-use protocol, see the contact persons and phone numbers in issue #174. ***** 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 Return address: ben@maggadu.Queernet.ORG -- ben@maggadu.QueerNet.ORG AIDS Info BBS 415)_626-1246 free since July 25, 1985