&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& Copyright 1992 by John S. James; permission granted for non-commercial use. AIDS TREATMENT NEWS Issue #163, November 20, 1992 phone 800.TREAT-1-2, or 415/255-0588 CONTENTS: [items are separated by "*****" for this display] Call to Activists: Focus Needed on Early Human Research How to Advocate and Build Coalitions for Medical Research Funding Protecting Body Composition in HIV Infection: Interview with Nutritionist Cade Fields Newman Announcements Berlin International Conference: Dates and Deadlines SEARCH Alliance Seeks Medical Director Baltimore/Washington Area Clinical Trials Directory ***** Call to Activists: Focus Needed on Early Human Research by John S. James The main obstacle today to better AIDS treatments is early in the drug-development pipeline. Hundreds of potential antivirals are coming out of laboratories and being published in leading journals, but almost none of them move further, through FDA-required animal toxicity tests and into early human trials. Once a potential drug shows biological activity in humans (by decreasing viral measures, or raising T-helper cells, etc.) , it would likely get enough attention to be developed appropriately. But without such data, a drug is usually ignored, because: (1) the scientists who developed it cannot finance clinical research; (2) pharmaceutical companies consider many factors other than medical or scientific ones in deciding whether to develop an AIDS drug; (3) the public has little consistent interest in a chemical which has never been tested in humans; and (4) the Reagan-Bush administrations did not take responsibility for managing the research effort. The resulting catch-22 -- no interest since there is no data, no data since there is no interest -- has blocked development of almost all potential AIDS drugs, and is still blocking them today. With the new administration, this critical problem could be fixed, allowing new treatments to come into use quickly if appropriate. As soon as there is evidence that a drug works very well, it is likely to move exceedingly rapidly into wider use. But if the same drug is never tested in people, or is only tested for toxicity in HIV-negative volunteers, the necessary evidence will not exist, and the drug will probably be delayed indefinitely. The big danger now is inertia, because no force is yet available to make the changes needed. Pharmaceutical companies are interested in short-term gain from drugs already on the market or soon to be there. Most influential AIDS researchers, even when supported largely by federal grants and contracts, also have business ties with these companies -- a situation which has long distorted research policy and prevented potential new drugs from being fairly considered. The Washington, D. C., AIDS policy organizations have not historically included research issues in their "corporate culture," and might not be able to challenge the research community when necessary; yet these organizations will manage the articulation of the AIDS consensus which will go to the Clinton transition team and administration. Some candidates now discussed as potential "AIDS czar" have avoided treatment issues, apparently due to unwillingness to challenge their scientific colleagues. In short, all the conditions are in place for a nightmare of business as usual, which could leave us, in several years, about where we are today -- with no major new antivirals and little advance in AIDS treatment except for refinements in the use of AZT, ddI, and ddC. AIDS activists can make the difference, by never letting the most critical issues in drug development be ignored. So far, however, early drug development is scarcely on the table among activists. It has been easier to focus on more immediate concerns, such as conditions for expanded access, or equity in access to clinical trials. These issues are also important, but without better drugs, they will not save many lives. The facts about excellent candidate drugs not getting into the development pipeline, or not proceeding coherently to the first tests of antiviral activity in humans, have been public knowledge for years. Yet this issue has received little attention until now, because until this month there was no chance of resolving it successfully. Such a pervasive, systemic malfunction cannot be repaired without national commitment and high-level involvement and support. The FDA could not solve the problem by itself; neither could the NIH; neither could any private organization. The necessary national mobilization would have required engagement and cooperation of higher Federal officials, which was not available. Our biggest enemy today is the inertia of 11 years of Federal AIDS mismanagement. What can defeat it is an ongoing determination to bring the most critical problems into the light of public and professional attention, to keep them there as long as necessary, and to insist that they be addressed. AIDS activists must take the lead in exposing the seriousness of neglecting the flow of new drugs into early clinical development. * * * Note: The following is our submission to the National Commission on AIDS, which is preparing recommendations for the new president and Congress. The Commission requested that these statements, which were due November 23, include specific recommendations to the executive and legislative branches. Better AIDS Drugs: The Biggest Obstacle To improve AIDS/HIV treatment and save lives of those already infected, the greatest need by far is better antiretroviral drugs. And the main reason progress in new drugs has been so disappointingly slow concerns obstacles near the beginning of the drug "pipeline" -- in the late preclinical and early clinical stages of drug development. This part of the development process has been overlooked, not because of scientific disagreements but because of systemic political and commercial snafus. It urgently needs more attention: * Because of improvements by the FDA, the blockage near the end of the drug pipeline has been greatly reduced; ddI, ddC, and now d4T have been made available. The problem is that no major anti-HIV drugs are now in the pipeline, except for some, like tat and protease inhibitors, which are still very early in clinical trials. Therefore, no important advances are likely from the mainstream drug-development pipeline for at least several years. (An FDA press release dated October 19, 1992 said that the FDA had "received" more than 500 IND applications "to test drugs or biologics that may have potential in treating AIDS and other HIV-related conditions." But when the press release listed "potential AIDS therapies publicly acknowledged by their sponsors to be under study," it had to stretch considerably to include any anti-HIV drugs. The following is the FDA's list of "INDs for experimental antiviral agents": compound Q, N-butyl DNJ, ribavirin, ddC, beta interferon, d4T, and AZDU. None of these is likely to be a major advance in HIV treatment, and some appear to be dead. Vaccines, which can also be HIV treatments, are listed separately; but there is considerable debate about whether any therapeutic vaccine has shown clinical benefit or is ready for large trials. And as for the drugs the FDA could not name because they had not been publicly acknowledged by their sponsors, none could have progressed to large human trials without being well known. In short, no important HIV drugs will emerge for some time. The image of hope and competence projected by the press release is an illusion.) * Dozens if not hundreds of potential anti-HIV drugs or lead chemicals have been produced in university and other laboratories, tested in viral cultures or in animals, and published in major, peer-reviewed journals. Usually development stops there, since no one involved has the money to finish the preclinical development required or to begin human tests. Since no public agency takes responsibility for shepherding these compounds into further development if justified, they usually wait indefinitely unless some pharmaceutical company picks them up -- unlikely when there is no data on biological activity in humans. * The existing AIDS trials networks (ACTG, CPCRA, CBCT) are focused on a later stage of research. Today they are often conducting dubious trials because they have no compelling drugs to study. * Some people believe that the National Cooperative Drug Discovery Group program (NCDDG-HIV) is addressing this problem. We have not attended their meetings, but we hear that they focus on theories of rational drug design -- which clearly will be the ultimate future of drug development, but so far has not been effective for AIDS. (Much of the focus is on improving high-tech tools such as computer imaging systems, but the drugs produced with those tools have not worked.) For the current epidemic, we also need empirical development of the most promising leads available, even those resulting from chance discoveries instead of high-tech science. But this work is undervalued because it is usually routine and not glamorous. * The bottom line is that we are suffering a serious imbalance in research, because the drugs which most need attention now for saving lives are not well positioned to build the constituency needed to motivate their continued development. Drugs which are already marketed, or almost ready for marketing, can develop industrial, medical, and public constituencies. Rational drug design generates both industrial and academic support. But no constituency champions a drug developed by one scientist or academic team, with no pharmaceutical sponsor, and with no human tests. Recommendations * The executive branch must take responsibility for proactively shepherding critical drugs through the development process -- not just wait for some pharmaceutical company to move. * The U. S. National Cancer Institute has shown that government can successfully carry out early human drug development when necessary. Both legislative and executive branches should expand this work. * The executive branch should set up a medical research ombuds office, where anyone who knows about research snafus of any sort can report them, and can expect to get action when appropriate. Most of the problems which block clinical trials or other research are red-tape accidents which could be cleared up by a few phone calls from an office with the president's authority behind it. When broader policy issues are involved, the office should research and prepare recommendations for the executive branch, for Congress, and for foundations, companies, and other private organizations. ***** How to Advocate and Build Coalitions for Medical Research Funding by John S. James Note: A treatment activist asked us for a memo which he could provide to a meeting on the Clinton transition, and we drafted the following in response. Because we assumed a friendly audience that did not need the humanitarian case restated, we focused instead on fitting medical research into Clinton's economic and political agenda. Because we could reasonably presume that AIDS will be treated fairly, we discussed medical research overall, not AIDS research in particular. This way we could focus on a universal appeal, since medical research is important to everyone. And this focus opens doors to coalitions with other health constituencies. In the past, we were advised to soften or omit the problems in medical research -- especially when Congress was considering funding. But now we have the prospect of a serious national commitment to AIDS, as well as a major national policy shift from military to civilian research. As a result, the problems themselves can be an integral part of research advocacy, since they point the way to highly cost-effective management efforts. Correcting key malfunctions which are preventing the translation of research investment into clinical benefits can release unimagined opportunities for achieving the results that count -- better practical treatments for people. One problem today is the belief in some circles that medical-research progress is a root cause of medical cost inflation, by producing better but ever more expensive treatments -- essentially an argument that in medicine, ignorance is cost effective. A closer look shows that cost inflation reflects mismanagement, not advancing knowledge. * * * Biomedical research is politically unique because it is personal in a way that other technologies are not. Everyone knows that they and their loved ones may (and probably will) face life-threatening illness some day -- and that medical science could make the difference between life and death, or between recovery and lasting disability. Medical research enhances the security of everyone. Other technologies also save lives, but the public does not see them the same way. For example, a recent poll of Maryland voters sponsored by Research!America found that 47 percent of voters were willing to pay more taxes to increase medical research -- several times the level of support for space or national defense. Biomedical research has other advantages: * If well managed it will reduce the cost of medical care. Treatments which work well are usually less resource-intensive than those which work poorly and require chronic care. Medical cost inflation stems from poor management, from incentives for inappropriate use of technology, not from medical advance itself. For example, in the Reagan-Bush administration, there was no proactive leadership to assert the public interest -- and since price competition in medicine is difficult to arrange within ethical constraints, the commercial incentives were to research and develop the most expensive (and therefore most profitable) treatments, even when less expensive approaches could work as well or better. * Medical research stimulates biotechnology, a major area of U. S. strength and a key element of the future U. S. economy -- if we do not lose the lead to Japan, which has long been ahead in certain areas, such as fermentation technology. On the other side, there is public impatience today with cancer, Alzheimer's, and AIDS research particularly, because of lack of productivity in delivering improved treatments and better survival and care. (Some medical fields, such as heart disease and ulcer research, have delivered major benefits.) In AIDS, where we have reported on research and treatment for six years, it is clear that major management problems are inhibiting progress, and that these can be fixed. For example, the biggest single block today to better AIDS treatments is the lack of a workable system for getting the best of the hundreds of promising drugs created in laboratories through preclinical and early clinical development, to the point of the first test of biological activity in 12 to 20 human volunteers. If the drugs could get to that point, it would be relatively easy to find companies to take the successful ones the rest of the way. Other major, systemic problems in U. S. medical research today include (1) the lack of viable career paths for physician/researchers (who are often required to cash in their M. D. chips due to accumulated debts before completing research training), and (2) the lopsided influence of industry on directing government research money, since almost everybody on the committees which allocate public money has pharmaceutical relationships on the side, resulting in grossly disproportionate research emphasis on large-company drugs already marketed or nearing the market, and no critical mass of advocates to champion newer, emerging technologies. (The latter problem may reflect not so much the excessive power of pharmaceutical companies, but rather the lack of countervailing assertion of the public interest, due to ideological objections in the outgoing administration.) No one in government (or elsewhere) has had the authority to attack these and other systemic problems. Much progress has been made in basic research, especially in the development of tools and techniques which open doors to progress against AIDS, cancer, and many other diseases. But we have not had the leadership to fix the obstacles blocking the translation of basic knowledge into better treatments and cures. With high-level attention, these obstacles can in large part be overcome, allowing us to harvest the benefit not only of ongoing basic research, but also of the great accumulated research investment already made. ***** Protecting Body Composition in HIV Infection: Interview with Nutritionist Cade Fields Newman by Dave Gilden The importance of malnutrition in AIDS progression is slowly receiving more attention. Specific micronutrient deficiencies have been found with HIV that effect immune system function or are related to brain and nervous system impairment. [See AIDS TREATMENT NEWS #134, September 6, 1991, "Zinc and B Vitamins in HIV: Overview and Interview," by Denny Smith; and AIDS TREATMENT NEWS #158, September 4, 1992, "Nutrition at VIII International Conference on AIDS," by Jason Heyman]. A broader issue is the loss of the protein stores located in lean body mass as AIDS progresses. Each individual seems to require a minimum store of protein to support life. There is an increasing awareness that death among people with AIDS frequently occurs when that limit is approached. People with AIDS may be dying from a process similar to starvation. Many generalized symptoms of advanced AIDS, including lack of energy and decreased ability to concentrate or cope independently, could arise from tissue disintegration caused by a loss of protein stores. The chronic, progressively debilitating aspects of AIDS and HIV infection require treatment as much as do the acute, life- threatening opportunistic infections. The two are interrelated. Ensuring proper nutrition is not just a matter of eating the right foods. It is a complex task requiring, among other things, management of illnesses, mental attitude and drug interactions. Sufficient physical exercise is also necessary to maintain or recover body composition. We spoke with Cade Fields Newman, M. S., R. D., about the multifaceted nature of nutritional support and its potential benefits. Ms. Newman is the founder of The Cutting Edge, a nutritional consulting firm in Fremont, California that specializes in advising patients with HIV. Besides working with individual doctors, she is currently organizing a nutritional assessment service for the Physicians Association for AIDS Care (PAAC). It will supply member physicians with an evaluation of the nutritional status of their patients and recommend ways to control nutritional deficits and wasting. * * * ATN: How important would you say proper nutrition is? CFN: Well, if I said I had a drug that would extend a patient's life two or three years, that would improve their quality of life, that would keep them in a situation where they could provide their own care and keep them working, you would think people would be flocking to it. Yet, we do have that; it's called "nutrition." Although not a stand-alone therapy, it is a very important part of overall treatment. And in conjunction with all the other things that are done, I believe that we can start dealing with HIV as a chronic manageable disease, where a person can live a normal, quality lifespan. ATN: It seems obvious that the earlier one starts a nutrition plan the better. Once you become sick and lose considerable amounts of weight, it will be hard to recover. So, where does one start? CFN: Yes, prevention is absolutely key for a person to have this vague thing called quality of life. But nutrition is not even a good stand-alone therapy to support nutritional stores. What is required is a strong partnership between patient and physician, hopefully with a multidisciplinary team's input. The patient has to be captain of a team. For instance, I'm a dietitian, but I cannot solve swallowing problems. You may need a speech therapist to evaluate that. Or there might be a problem with peripheral neuropathy and carrying out the tasks of daily living. Then, an occupational therapist should come in, or if there are problems with range of motion or movement, a physical therapist. There should be a pharmacist to advise on the effects of medications on nutrient utilization. Also, there are the nurses. Patients see them more than anyone else, especially home-care patients. All of us are simply advisers. It's the patient's choice. It is very important that they can assemble this team and that it does what they want. Otherwise people get advice on nutrition from persons who do not have access to their medical records. There is no way such persons can put together nutritional advice that matches that person's individual medical profile. ATN: But nutritional advice is not all that common at a physician's office. Most doctors don't have much nutritional training. How common is this ideal sort of team that you are talking about? CFN: It varies from place to place. It occurs when you have strong-minded, assertive patients who insist on it. It's a growing phenomenon. A lot of us talked about team work for years without doing anything about it, but now patients are insisting on it. The doctor has to be in tune with what's happening. If the patient cannot maintain adequate nutritional stores, then medical therapies will fail. Drug therapies depend on your protein stores, for instance on your serum albumin to carry that drug where it needs to go. Oral drugs depend on your ability to absorb. That, too, is based on nutritional status. At least, primary care physicians need to monitor overall treatments to make sure that they do not conflict. That cannot be done unless people are working together as a team. ATN: I want to talk about what this team will advise in nutritional support. But first can we briefly describe the sources of inadequate nutritional balance in HIV infection and AIDS? CFN: There are three major reasons for malnutrition in HIV- related disease. The first is decreased intake. That could be because of anorexia -- just a lack of appetite -- which could happen with depression or some of the drug interactions, a number of different things. The second part of this is malabsorption, which happens quite often with HIV-related diseases in the gastrointestinal track. These two considered together would be reasons for the body to starve. Besides this, the inflammatory response of the body to HIV uses up protein stores in muscle tissue. This creates a major risk for malnutrition. Also, the altered metabolism of nutrients allows a person to hold onto and even generate fat stores while maintaining or building lean tissue is difficult. Nutrient transport within the body may also undergo alterations. For instance, in a number of patients with advanced disease, there are indications of an iron deficiency although there may be other signs that there is plenty of iron. It looks like iron is not going where it needs to go, and just supplementing with iron is not going to help. The picture is much more complex than not getting enough food or malabsorption, and that's what makes nutritional intervention so difficult. Often we talk about this particular chemical in the body doing that particular thing, but there may be many different metabolic pathways that have to be set right. ATN: OK, so let's start at the simplest level. What are the first steps an asymptomatic person with HIV should consider for nutritional intervention? CFN: Well, I know it's not hi-tech, but food is going to be the best thing a person can do. When we second-guess nutrition and try to package it into little things to give people, we sometimes get into trouble. Food has many substances in it that we don't know much about and that might be very important. If I were to prioritize what a person needs, the number one priority would be fluids because without adequate hydration, nothing works. The second priority would be calories, because without enough energy it doesn't matter what you are getting in terms of protein. It will not go where it needs to go. The third priority is protein, and the fourth priority is vitamins and minerals, which cannot be used by the body without the first three. ATN: It's important to stress that problems with food intake might be problems with energy -- not preparing food or feeling energetic enough to eat. CFN: Absolutely. You need to figure out for each person what they need, what they're getting, and strategies for getting it. And when they're having a bad day, they should have a stash of food on board. Many people do not have that, and when they go through two or three bad days, they get behind. At least if they had a supply of food supplements, even instant breakfast, they could get through better. Cooking can be very energy-draining; don't feel strange about asking for help. If someone wants to cook for you, let them do it. Nutrition covers quite a span. Sometimes we get so caught up in the biochemical changes in the liver, when a simple chair in the kitchen or a better pair of eyeglasses would make the biggest difference. For a person who is completely asymptomatic, a basic piece of advice is to learn fundamental nutritional principles. Learn how nutrition interacts with immunity -- from a serious source, not from some popular magazine. Food safety -- proper storage, cleaning and cooking -- is another very important skill to learn. There are a number of opportunistic infections that could be prevented if food safety were higher on people's lists. ATN: Isn't there data that you should start collecting to check on your nutritional status? CFN: Yes, you should develop some individual strategies you can put together to make sure you are getting what you need on a day to day basis, but you should also develop a good contact that will answer your questions and monitor your body composition every six months. Weight is not a good early indicator; its loss shows that a lot of things have already happened. It is very important to get baseline data so you can know what the trends are in mid-arm circumference and triceps skinfold [a measurement of fat stores] and so forth. These measurements reveal more than weight alone does about the present state of body composition. You also need to monitor medical therapies. Many people are taking many medicines. Drug interactions with the body, such as nausea, vomiting, diarrhea, and toxicities to liver, kidney and pancreas, can put you at risk nutritionally Another factor to monitor is markers of nutritional status. Albumin in the blood is a good general indication of the state of the body's protein stores, although infections can make this go down without any relation to nutrition. ATN: Are there specific nutrients that you would suggest emphasizing in the diet? CFN: I would concentrate on a nutrient-dense diet. This means that calorie per calorie you get a good amount of the other things you need, like protein and vitamins and minerals. Your priorities are still fluids, calories and proteins, and then micronutrients [vitamins, minerals, etc.]. Most people ask about vitamins, but you need the first three to get any benefits at all from the last one. I would concentrate on fluid-containing, calorie-containing and protein-containing foods and then make sure I got adequate micronutrients. A group from the University of Miami in Florida did recommend some very specific things in regard to supplementation [M. K. Baum and others, "Interim Dietary Recommendations to Maintain Adequate Blood Nutrient Levels in Early HIV-1 Infection," VIII International Conference on AIDS, Amsterdam, July 19-24, 1992, abstract #PoB3675]. In early HIV infection, increased intake of zinc and vitamins B2, B6, B12, A [or beta carotene equivalent], C, and E, on the order of six to 25 times the RDA [depending on the nutrient; more than six times for some of them could be harmful. See full report in M. K. Baum and others, "Influence of HIV Infection on Vitamin Status and Requirements," ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, volume 669, pages 166-174], was found necessary to maintain adequate blood levels of these substances in some patients. We don't know yet how helpful normalizing these values is going to be. This is just an interim recommendation. But we have seen people improve cognitive function by normalizing B12 -- an important nutrient to pay attention to if there is a decline in its level. Similarly, B6 seems to be important in protecting against neuropathy, although an overdose of B6 also causes neuropathy. A generic recommendation would be just to eat adequate foods and from there add a multivitamin maybe once or twice a day. You have to be careful about what you're taking. Nutrients, like drugs, can be very toxic, especially for people with HIV. A number of HIV-positive people may already have problems with chronic hepatitis or other organ infections. If you have liver or kidney dysfunction or any pancreatic dysfunction -- maybe you have been on ddI -- nutrients are not metabolized in the normal way. And a number of drugs are toxic to the liver. This adds to the potential compromise and toxicity when you take something like vitamin A. ATN: Do you favor other special dietary supplementation? CFN: If a person cannot take in enough calories -- maybe there's a problem with swallowing or someone just cannot fit in the nutrients they need -- you can go to the calorie-packed liquid supplements. You can use those to augment nutrition, preferably, and in some cases replace whole meals. Stocking up on these oral supplements is another way of preparing for bad days. A different kind of supplementation is exercise. Regular exercise is highly beneficial. Also, if you want or need to gain weight, then you need to do so along with exercise because padding yourself with fat is not particularly helpful. If an opportunistic infection occurs, you need protein stores to resist it and make your drug therapies work. There is a high correlation between muscle mass and clinical well-being. Protein makes the body function; immunity is based on protein stores, too. And exercise promotes protein formation in tissues throughout the body. Here, resistance exercise, like body building, is more important than aerobic exercise. Another strategy that promotes protein-building is regular, frequent meals. One study found that people who eat at least four times a day, including a snack an hour or so before sleeping, did better in terms of nitrogen balance than anyone who ate less than four times a day. Fortifying protein stores should be a central preparation for coping with AIDS. ATN: When severe immune deficiency does come about, what are the issues then? CFN: Most people who lose weight in conjunction with an opportunistic infection have a hard time gaining it back, if they ever do. And when they do gain it back, they may not gain back the protein stores they need, just fat and fluids. This is the central problem. ATN: Aren't there ways to recover? CFN: Yes, there are four strategies for regaining lean body mass, and nutritional support is only one of them. The first defense is prompt and effective treatment for opportunistic infections when prophylaxis fails. We can prevent much malnutrition by stopping the cascade of events surrounding opportunistic infections. The second line of the defense is hormonal modulation and anti-inflammatory therapies. Some patients have low testosterone levels, for example. By replacing that, you can maintain or increase lean body mass because that's one of the effects of testosterone. Elevated cytokines, such as some interleukins, have been proposed as causing the wasting effect. I'm not so sure that anti-cytokines will prove to be a good therapy by themselves, but perhaps they will be helpful in conjunction with other treatments. Anti-inflammatory agents abound. You have to be careful to block the harmful aspects of inflammation, those that drain protein stores for energy, and not the beneficial ones. Simple aspirin and fish oil reduce the level of inflammatory prostaglandins to give the body an opportunity to recover lean tissue. Fish oil may be more effective earlier rather than later, though. ATN: You mentioned how important exercise is early stages of disease, but does it have an effect later on, when movement is harder? CFN: Yes, exercise is the third defense strategy. It is still important in protecting body composition or gaining back lean body mass after you have lost weight. It's tough when you are experiencing a lot of fatigue or physical limitations, but there are people who can put together exercise programs even for those who are in wheelchairs. ATN: And nutritional support is the fourth strategy? CFN: Finally, we come to ensuring an adequate diet. In AIDS, a host of opportunistic infections affect eating. We mentioned aspirin before; that and other anti-inflammatories are also used for pain management. Pain management is an issue that is not fully addressed for many people with AIDS, and it can be key, not only for overall quality of life, but also for the ability to eat. Just about everybody with AIDS will have diarrhea at some point, despite attention to food safety. Treating the underlying cause of diarrhea, if possible, is the most effective course of action. Also, anti-diarrhea drugs may be combined with nutritional strategies. Fasting during episodes of diarrhea is not recommended. Emphasizing sources of soluble fibers (such as bananas, oatmeal, applesauce and potatoes) while removing sources of crude fiber and maintaining an overall balanced diet is more appropriate. Replacing lost fluid and electrolytes, especially potassium and sodium, is crucial. ATN: Rehydration and electrolyte replacement can take place intravenously as well as through the diet. Eventually, simple dietary techniques may not be enough to provide sufficient nutrition. Liquid food supplements can be added when someone cannot or does not take in enough food for whatever reason. Feeding through a tube to the stomach also has its place in people physically unable to eat. But in the extreme case, there is parenteral feeding (through a catheter attached to a vein), which avoids the GI tract entirely. What role does it play? CFN: Partial or total parenteral nutrition can help people get over the hump when disease causes extreme malabsorption. It is necessary to start early, though. Don't let people not eat for three to fourteen days before introducing parenteral nutrition. Parenteral nutrition does not have to be permanent. People feel that if they go on TPN [total parenteral nutrition], they're stuck with it forever. That is not true. In certain diagnoses, such as CMV colitis, people may be maintained on TPN throughout their lifetime. Even then, they can modify oral intake and in some cases reduce their dependency on TPN. The second point I would like to make is that aggressive support does not equal TPN. You can be aggressive with peas and carrots and palliative with TPN. To find out what the appropriate support is, the patient can be clinically profiled into diagnostic sub-groupings. For instance, if the person is experiencing some depression and is adequately absorbing nutrients, they may simply need to focus on "maximizing food intake," by eating nutrient-dense foods. ATN: What about using Megace [synthetic progesterone] or Marinol [synthetic THC, the active ingredient in marijuana] to stimulate appetite? CFN: Marinol seems to work well for nausea, and some patients prefer it for increasing appetite. Some people complain about feeling drugged out, though. Some say that smoking marijuana works better. It's quicker, and avoids their queasy stomach. But the smoke can present a problem, especially for those with respiratory infections. Patients on Megace tend to gain fat, according to studies using therapeutic doses of 800 mg/day. Many people use a lot less than that. It has been speculated that a slow weight gain associated with lower than established therapeutic doses may include more lean body mass. When used with people who have a mechanical or pain reason not to eat (rather than reduced appetite), Megace may be detrimental through increasing the desire and not the ability to eat. In advanced HIV infection, you may have "futile cycling" of fat going on, where fat stores are broken down in the liver and then rebuilt by the liver. This wasteful process results in consumption of body protein for energy. If you throw rehabilitative levels of calories at someone in this state, you may just get more fat and not the protein stores that are needed. ATN: Appetite is closely tied to mental outlook. And mental outlook can be impaired by not eating. This brings up the relation of mental health support to nutritional therapies. CFN: Help in avoiding depression or handling stress becomes more and more necessary as HIV infection progresses. It is key to motivating HIV-positive people to follow other therapies. Again, nutritional support, like medical support, will not be most effective all by itself, as a stand-alone therapy. ATN: Also, speaking of specific substances like Megace or Marinol, I notice we haven't spoken much about specific vitamins and minerals later on in the disease. CFN: The significance of vitamin and mineral deficiencies are not well established. Other micronutrients that we look at besides the ones mentioned before in connection with the University of Miami group include selenium and folate. One doctor I know has had good results improving patients' quality of life with magnesium supplements. But micronutrient deficiencies seem to be geographically dependent. Some of this has to do with the minerals in the local soil. A major factor is the variation from place to place in the way physicians treat AIDS. Drug interactions have a large influence on micronutrient absorption and utilization. For example, pyrimethamine and trimetrexate, which are used in treating toxoplasmosis and pneumocystis, interfere with folate metabolism. ATN: So, when taking vitamins and minerals, you have to understand the roots of the deficiencies? CFN: Oh yes. Blood indications of low iron may not be resolved by iron supplementation if it is really a cellular level nutrient transport problem due to low protein stores. You need to see what is best for the patient. If micronutrient levels normalize, is that valuable, or are other things going on that are still disruptive? Again, addressing problems that may cause alterations in nutritional, and specifically micronutrient, status may be most effective. ATN: Where patients find reliable information about nutrition, and learn more about the full potential for dietary changes to modify disease progression? CFN: Patient information is available through a number sources. To get a listing of educational pieces designed for HIV patients you can contact the National AIDS Information Clearinghouse at 1-800-458-5231. To find dietitian services for evaluation and counseling, request a referral from your physician. The next step is to locate a dietitian who has training and experience in HIV- related nutritional issues. Also, contact major city public health departments and ask for phone numbers of AIDS nutritional networks. In the New York area, you can contact Nutritionists in AIDS Care at 212-439- 8073. Arizona, California and other states have networks as well. Several AIDS support agencies have added dietitians to their staffs, including the San Francisco AIDS Foundation, and Bronx AIDS Services. Local home meal delivery services can also be a place to start. [Note: To contact HIV nutrition specialists at The Cutting Edge, the organization founded by Cade Fields Newman, call 510- 797-9768.] ***** Announcements: ** Berlin International Conference: Dates and Deadlines The major international AIDS conference of 1993 will be the IXth International Conference on AIDS, Berlin, June 7-11, in affiliation with the IVth STD World Congress. Abstracts, on an original copy of the form provided by the conference and with five photocopies, must be received no later than January 15, 1993. Advance registration before January 31 is at a reduced rate, DM 800 regular and DM 250 student. After January 31 and on site, registration is DM 950 regular and DM 350 student. The conference phone number is 49-30-857903-0; fax is 49-30- 857903-27. ** SEARCH Alliance Seeks Medical Director SEARCH Alliance is seeking a medical director to develop and manage community-based clinical trials in Los Angeles. Candidate should be an M. D. with strong clinical skills, HIV/AIDS clinical trials experience, and knowledge of research methodology. Send curriculum vitae to: Board of Directors -- Medical Committee, SEARCH Alliance, 7461 Beverly Boulevard, Suite 304, Los Angeles, CA 90036, phone 213/930-8820, fax 213/934-3919. ** Baltimore/Washington Area Clinical Trials Directory A directory of more than 50 AIDS/HIV clinical trials recruiting volunteers in the Baltimore and Washington areas has been published by AIDS Action Baltimore. The directory includes trials at Johns Hopkins University, the University of Maryland, Georgetown University, the National Institutes of Health, Walter Reed Army Institute of Research, Whitman-Walker Clinic, Chase- Brexton Clinic, and other locations, including community-based trials through physicians' offices. Vaccine trials (for HIV- positive volunteers), pediatric studies, and expanded-access programs are listed. The 36-page directory includes a trials index, a glossary, and notes on other relevant publications and resources. For a copy of The Directory of Clinical Research in AIDS for Baltimore & Washington, September 1992, contact AIDS Action Baltimore, 2105 North Charles St., Baltimore, Maryland, 21218, phone 410/837-2437. ***** 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 1992 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. &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&