Date: 23 Aug 94 21:54 PDT From: "John S. James" Lines: 1041 AIDS TREATMENT NEWS Issue #205, August 19, 1994 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS Human Growth Hormone Reverses Wasting in Clinical Trial Yokohama Conference Overview BARRON'S: "Do We Have Too Many Drugs for AIDS?" Major FDA Public Meeting on Early Access, Accelerated Approval, Sept. 12-13 Nutrition and AIDS: Interview with Kristin Weaver (Part 2) ***** Human Growth Hormone Reverses Wasting in Clinical Trial by John S. James A multicenter placebo-controlled trial with 178 volunteers has shown clear evidence that human growth hormone can reverse wasting syndrome, which causes many deaths in cases of advanced AIDS. It is the first treatment for wasting which has been proven to consistently restore lean body mass, according to principal investigator Morris Schambelan, M.D., an endocrinologist at San Francisco General Hospital. The data was analyzed immediately before the Yokohama conference and first reported at that meeting. The results were not surprising, because there have been positive anecdotal reports from patients and physicians involved in the trial. To be eligible for the Serono study, patients had to have lost at least 10 percent of their pre-illness weight, or to weigh less than 90 percent of their ideal body weight; those in the trial had lost an average of 14 percent. Since the hormone could not work if people did not eat, study volunteers had to be able to eat at least 75 percent of their estimated caloric requirement. Exercise may also be helpful, but the study did not prescribe it, due to the difficulty of designing an exercise program suitable for a scientific study; participants were not discouraged from exercising, however. In the trial, 90 volunteers received growth hormone (an average dose of 6 mg per day -- 0.1 mg per kilogram -- administered subcutaneously each day) and 88 received placebo for three months; after that time, all were given "open label" access to the drug, and some have been on it for up to two years, providing additional information about long-term safety. During the trial, patients in the placebo group initially gained an average of one pound, but lost most of this again during the three months. Those in the growth-hormone group gained an average of more than three and a half pounds, and have sustained or increased this gain afterwards; several patients eventually gained more than 20 pounds while on extended treatment. More interesting was an average gain in lean body mass of more than six pounds during the trial. Since this is more than the weight gain, it means that participants lost an average of about three pounds of fat. In this study, lean body mass was measured by a high-tech system called DEXA (dual energy X-ray absorptiometry), which is generally used for measurement of bone density, but has been adapted for measurement of body composition. However, a much simpler system known as bioelectrical impedance has been shown to be comparable to DEXA. There were five deaths among the 178 volunteers during or shortly after the three-month trial; three were receiving the hormone and two were on placebo. These deaths were due to infections in persons with very low T-helper counts. (The average T-helper count of the persons in the trial was 84, with half of them being below 50.) Human Growth Hormone -- Background Human growth hormone is a prescription drug which has been approved in the U.S. for several years for treating growth- hormone deficiency in children; it is currently sold by Genentech Inc. (trade name Protropin) and by Eli Lilly and Company (trade name Humatrope). The recent trial, however, was sponsored by a different company, Serono Laboratories Inc., which has its own human growth hormone which is now approved in 50 countries but not in the U.S., due to exclusivity provisions of the Orphan Drug Act; that exclusivity ran out in March 1994, and the company is now seeking FDA approval for treating children with growth- hormone deficiency, in addition to investigating the drug's efficacy in the wasting syndrome. There are slight biological differences between the versions of human growth hormone sold by the different companies, with the Serono product being derived from mammalian cells, and the others from bacteria. There is no evidence that the products act differently in people, however. When used to treat wasting syndrome, human growth hormone seems to work by a direct effect on protein metabolism, not necessarily by correcting a growth-hormone deficiency. Since human growth hormone can cause various side effects, it must be used cautiously. Unfortunately, human growth hormone is very expensive. Increasing competition may reduce the price somewhat, but it will still remain an expensive drug. With the new study, there is now a strong case for its medical necessity in some AIDS patients; this should make reimbursement easier. (An earlier study was published in 1993 (1); this should strengthen the case for reimbursement.) Serono is now sponsoring another large controlled trial, with 180 patients, one third of whom are receiving placebo. This trial will focus on additional safety data, to satisfy the FDA. Once the product is approved specifically for AIDS wasting, reimbursement should be automatic. Nutrition for HIV-Associated Wasting -- Brochure Available Serono Laboratories is producing an educational brochure of nutrition information for persons with wasting syndrome; it is useful regardless of whether human growth hormone or any other treatment is used. The text appeared in the June 1994 issue of BETA (Bulletin of Experimental Treatments for AIDS) published by the San Francisco AIDS Foundation. For a free copy, call Gina Cella at Serono, 800/283-8088 ext. 5251, or write to her attention at: Serono Laboratories, Inc., 100 Longwater Circle, Norwell, MA 02061. References 1. Mulligan K, Grunfeld C, Hellerstein MK, Neese RA, and Schambelan M. Anabolic effects of recombinant human growth hormone in patients with wasting associated with human immunodeficiency virus infection. JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. 1993; volume 77, number 4, pages 956-962. ***** Yokohama Conference Overview by John S. James The Tenth International Conference on AIDS, August 7-12 in Yokohama, Japan, generated the usual media gloom about the lack of effective treatments. The gloom is understandable; AIDS treatment development has been a disaster (despite all the attention to the one major success of the last year, the two-thirds reduction of transmission of HIV from pregnant women to their babies by use of AZT). But the press did not report the intense interest behind the scenes, the fact that this conference may have marked the release of more useful scientific advance than any other. For example, research into long-term survivors, and other studies of the pathogenesis of HIV disease, started being taken seriously about two or three years ago, and the results are now coming in. It is now widely suspected that there are some people who are infected with HIV but who may never progress to AIDS or other illness. And careful laboratory studies of ten long-term nonprogressors, reported by David D. Ho, M.D., of the Aaron Diamond AIDS Research Center, found that the T-helper cells of these people had no special resistance to HIV infection, and yet the level of virus in their blood was extremely low. What seemed to be protective was a very strong immune response, mainly due to their CD8 cells, and also due to neutralizing antibodies. (Other researchers have found that some CD8 cells produce a soluble substance, which has not yet been identified, which prevents the growth of HIV; it is now known that this substance works as an inhibitor of the LTR, the long terminal repeat, of the virus.) Also, the virus in those nonprogressors often appeared to be defective or attenuated. While information like this does not immediately provide a new treatment, it provides guideposts for understanding what needs to be done to control HIV infection, why the current drugs are not doing so, and what might be needed in drugs which would work better. This does not, of course, give people something they can use today. HIV RNA Tests What we believe is the most important development that people can use now -- although it is still experimental, and just beginning to come into clinical practice -- is measuring viral load or viral activity by testing for HIV RNA, either by quantitative PCR or by the branched DNA (bDNA) assay. These tests, which tell how much virus is circulating in the blood plasma, were discussed in detail in our last issue (AIDS TREATMENT NEWS #204, August 5, 1994), which was published before the conference; and we went to Yokohama primarily to learn more about this development. We were surprised by the breadth and depth of research interest, with RNA testing coming up in session after session, and much new data reported. The strong consensus of the researchers is that the level of virus in blood plasma can be tested accurately and consistently with the RNA tests, and that this measurement probably does provide useful information about how well treatments are working, although this is unproven until more research is done. Some are concerned about RNA tests coming into routine use in clinical practice at this time, before more is known about how to use them, but it is widely recognized that increased clinical use is imminent. Why do we believe that this is important? One reason is when a person is about to start a new antiviral drug, or make a change in their ongoing antiviral treatment (such as a different dose, or a different combination therapy), it is now possible to get a good idea, within about a month, of how well the new treatment is working for them. They need to get a baseline test before making the change, and then get the test again a few weeks later, to see if the level of virus in the blood has gone down, and by how much. (The RNA level can change very rapidly, even in a few days, so it is necessary to get the baseline test before starting the new treatment, in order to test that treatment correctly; it is not good enough to be tested shortly after starting.) If the new treatment is not an antiviral, but some other kind of treatment for HIV disease such as an immune-based therapy, then the HIV RNA test might still be useful, as a measure of whether the treatment is helping the body to control the virus. But much less is known about how to interpret the test results in this case; we will have to learn, either from clinical trials or from clinical experience, what can be expected from various treatments, and how long it may take for the level of virus in the blood to change. Also, note that RNA measurements can be used in the same way to test a "mainstream" treatment (such as AZT or ddI), or an "alternative" treatment (such as herbal or other substances that may have anti-HIV activity). As a result, there is now more reason to be interested in alternative treatments than there used to be. This is because the biggest problem with many alternative treatments was that there was no way to ever find out if they were working -- since there would never be enough money or other resources to run a clinical trial powerful enough to see if the treatment helped the "average" patient. Now it is possible to watch the effect in an individual person; and if the effect is striking enough, and is seen often enough, then the resources will be mobilized to run a formal trial and get a general answer. As a result, the hundreds of unproven treatments that people do use will now, for the first time, have a chance to prove themselves; the best are likely to come to light and move forward into trials. The resulting contribution to better AIDS treatment could be incalculable. Practical Treatments There were few practical treatments reported in Yokohama which were not already known before the meeting. But the results of a trial of human growth hormone as a treatment for wasting syndrome became available to the researchers only in recent weeks, and were reported in Yokohama for the first time. We interviewed the presenter afterwards, and summarized the results in an article which appears in this issue. There have been other trials of human growth hormone for wasting syndrome, but this one is by far the largest and best designed. There were many other reports which were suggestive of new treatment possibilities, or which may have immediate practical use for physicians and patients. We are still reading the conference materials and contacting experts for additional information, which we will present in future issues. ***** BARRON'S: "Do We Have Too Many Drugs for AIDS?" by John S. James The August 15 issue of BARRON'S (the Dow Jones business and financial weekly) has a cover article, "Do We Have Too Many Drugs for AIDS?" The cover includes the following summary: "In a turnabout, some AIDS activists are now asking the government to slow down its drug-approval process. What it means for pharmaceutical companies." Inside the paper, the article is titled "Rushing to Judgment." Its main points are that the FDA's accelerated- approval process for speeding the approval of drugs for AIDS, cancer, and other serious and life-threatening diseases has not worked, and that AIDS activists are calling for the FDA to go back to requiring placebo trials -- even if they take thousands of patients and require many years for drug approval. This article addresses a subject which has become bitterly controversial among AIDS activists. But it only presents one side. Some widespread concerns are: * The article is likely to damage AIDS, cancer, and other research by making it less attractive to investors, if they think that accelerated approval is about to be abandoned, and that activists are likely to oppose approval of their drugs by the FDA. * Much of the article concerns AIDS treatment activists -- which carries the piece journalistically, as otherwise there would certainly not be a cover article, and probably not an article at all. Yet there is not a shred of evidence that the reporter talked to any AIDS activist outside of a single organization -- the Treatment Action Group (TAG), located in New York, which has taken positions strongly opposed by other treatment activists and people with HIV. The article mentions TAG, but does not identify the only two activists it interviewed as TAG members. And it devotes less than half a sentence to acknowledging that other views exist. But we have found little support for and much opposition to the "activist" view described in the BARRON'S article, that the FDA should delay approving new AIDS drugs in the name of better data. Instead, once safety and activity of a drug have been shown, people want the freedom to make their own choices. But most patients and physicians have not heard that the controversy exists, and have no idea what is being advocated in their behalf. * In discussing placebos, the article states, "While commonly used in many other drug trials, placebos have been an anathema in tests of AIDS drugs, in large part because AIDS activists have vehemently protested against them." In fact, placebos are commonly used in AIDS trials, with little or no protest; for example, a placebo was used in the human growth hormone trial reported in this issue, and while we know two volunteers in that trial, and activists who have protested other aspects of the study, we have not heard any controversy about the placebo. The real controversy is not about placebos, but about trials designed to find statistically significant differences between two or more treatments in the number of deaths or major illnesses, often euphemistically called "clinical endpoints." These trials present special ethical issues (whether or not they use a placebo), because those who design and conduct them know very well that unless they get quite a number of these "endpoints," enough for statistical proof, the whole trial will have been a waste. In theory, the accepted standard of ethics demands that such a trial not be run unless it really is not known which treatment arm is best. But in practice, investors are unlikely to pay for the trial unless they have reason for confidence about the outcome. Placebos are not an issue if the trial is designed to catch people and get them into appropriate care before serious damage is done. But how can one reconcile this approach to patient care with a trial which is designed to record serious damage and count the bodies? Clinical Trial Design How, then, will we ever test drugs and know for sure what works, what keeps people alive longer? Our full answer to that question would not fit into this short article. But the first step is to realize that comparing the time to death or deterioration implies that one is testing marginal treatments. And these tests take several years, meaning that we must wait several years for the definitive answers about drugs already known to be marginal several years ago. Do we really want to structure much of AIDS drug development around getting good data, years late, on bad drugs? The alternative is to realize that nobody can predict in advance what is going to work. Therefore, we need to design drug development systems so that hundreds of potential treatments and approaches have a chance to begin to prove themselves and build credibility, bit by bit, if they are able to; eventually the best of these could progress into formal trials of various kinds. But until now, the barriers to any movement by new treatments and new ideas have been so high that few can move at all without major corporate support. Very few of them will have such support in the beginning; and if it is true that no one can know in advance what will work, then it follows that the drugs which do get corporate support are not really the best prospects, but are essentially selected at random. And the rest remain stuck forever. The new blood tests for viral RNA will allow some treatment ideas to begin to move. Drugs which are already in human use, or which can easily be used in clinical practice, will now be able to begin developing credibility, if they merit it. We should work with technological change to design more flexible, individualized drug development, instead of imposing rigid doctrines to address the problems of the past. Consensus Statement Circulated -- How to Sign On Project Inform is circulating a two-page "Consensus Statement on Accelerated Approval, August 5, 1994." It supports the current system of accelerated approval for early access to new AIDS treatments, against proposals to make the system more restrictive. Project Inform is seeking sign-on by organizations, and most importantly by HIV physicians. Current signers include the Community Consortium (which represents most of the HIV physicians in San Francisco), ACT UP/New York's Treatment and Data Committee, Project Inform, AIDS TREATMENT NEWS, BETA, SEARCH Alliance, and Mobilization Against AIDS. Project Inform can fax or mail you a copy; call them at 415/558-8669. Project Inform is also encouraging individuals and organizations who want to support early access and accelerated approval to write to Commissioner David Kessler, mail code HF-1, U.S. Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857. ***** Major FDA Public Meeting on Early Access, Accelerated Approval, September 12-13 A two-day public meeting of the FDA Antiviral Advisory Committee is shaping up as one of the important AIDS policy and community meetings of the year. It is important to let the FDA and the pharmaceutical industry know that the AIDS community insists on early access to new treatments, and strongly supports accelerated approval. The meeting location is not set as we go to press, but it will be in the Washington D.C. area. The following is from a fax we received from the FDA on August 17; we have edited it slightly for clarity: "The meeting is the 12th and 13th of September. Since there are going to be three other meetings within a month on surrogate markers, we are going to focus more on early access and accelerated approval at the two-day meeting. It will also be different in format, with much more time for public comment, and several times scheduled for comments. There will be a fax mailing announcing details soon through the AIDS coordination office. "In brief, the meeting will start with a history of making drugs available early for life-threatening conditions, in particular looking at the oncology experience. We will review parallel track and treatment INDs as they have been used in HIV drugs. There will be a point on the agenda here for comments on access issues, standards for widespread use, and the effects of widespread use on clinical trials and drug approval. Hopefully both the community and industry will share their perspectives. I think since d4T was approved that this is the first time in many years that there hasn't been an active parallel track or treatment-IND program in effect. "Second, the meeting will look at the historical examples of the use of accelerated approval: ddI (accelerated approval in practice, although not in name), ddC/AZT, clarithromycin for MAC treatment, and d4T. We will look at the evidence available at the time of approvals, the pace of confirmatory trials, what we have learned from each of these examples. "Third, we will look for specific proposals to improve the process of early access and accelerated approval. This would be a time, for example, when TAG or anyone else who would like to present the LST [large simple trial], or any other proposal, could put it on the table. There have also been some suggestions about bringing accelerated approval drug candidates to the Advisory Committee early in their development to get consensus on a reasonable portfolio of trials, and proposals to strengthen the confirmatory trial requirement process. I am sure there are others. "The Advisory Committee will not be asked to formally vote on any specific issue. The emphasis instead will be on open and wide-ranging comments on how to best use these tools in the future (including dealing with products still under accelerated approval). We will try to develop a document with points for a sponsor to consider when developing a drug that is a candidate for early access. "Anyone wishing to speak for longer than 5-10 minutes should send us a request, including the topic, so we can arrange an agenda. There will be time for comments not scheduled, but they will need to be brief. Requests to speak can be sent through Lee Zwanziger, FDA, CDER, HFD-9, 5600 Fishers Lane, room 8B-45, Rockville, MD 20857." Note: Persons who want to send a written statement to the Antiviral Advisory Committee should also send it to Lee Zwanziger at the above address. She is the executive secretary of the Committee. Note: The three other meetings on surrogate markers [such as HIV RNA tests], mentioned above, include: (1) "Surrogate Markers of HIV: Strategies and Issues for Selection and Use," October 12-14, at the Sheraton National Hotel in Alexandria, Virginia. The organizer is Cambridge Healthtech Institute, Waltham, Massachusetts, 617/487-7989, or fax 617/487-7937. The press is invited. (2) "FDA Accelerated Approval: Dealing with Uncertainty," Friday, September 23, at the American Academy of Arts and Sciences, near Harvard Square in Cambridge, Massachusetts. This meeting is sponsored by the Tufts Center for the Study of Drug Development, ML Strategies, Inc., Project Inform, and Gay Men's Health Crisis. The organizer is ML Strategies, Inc., Boston, Massachusetts, 617/542-6000. We could not reach the person in charge before going to press. We could not find out about the third meeting by press time. ***** Nutrition and AIDS: Interview with Kristin Weaver (Part 2) by Tadd Tobias and John S. James [Note: This is the continuation of the interview with Kristin Weaver, R.N., M.S.N., C.N.S.N., of the Bay Area Nutrition Counseling Center and Clinic (BANC) at San Francisco General Hospital. Part I appeared in our last issue, #204; copies are available from AIDS TREATMENT NEWS, 800/TREAT-1-2. Note the resource list at the end of the interview.] Nutritional Supplements ATN: What about nutritional supplements like Ensure? KW: People should be working with a dietitian or physician who really knows these products and knows which will be appropriate for each individual, because they can be expensive (about $20 a six pack for some kinds). Ensure is a good supplement but may not be appropriate for someone with fat malabsorption (often present in HIV disease). Because of its high percentage of fat, Ensure can exacerbate the diarrhea. Advera is fairly new, with fish oil and medium- chain triglycerides. It has a different kind of protein, a peptide, that is easily digested. Other supplements include, but are not limited to, Vivonex, Nutren, Peptamen, etc. In general, you might want to look at supplements which have a large percentage of medium-chain triglycerides (MCTs), which are a form of fat that is readily absorbed. We did a study for fat-malabsorbing diarrhea using a product with a high percentage of MCTs. The diarrhea decreased by at least half its original amount following the use of the MCT product and a low fat diet. ATN: Which product? KW: Lipisorb. Nutren is also excellent, and perhaps more tasty. I say this because our nutritionists routinely involve us in taste tests of all liquid supplements; if we're going to recommend supplements for our patients, we need to know how they taste, too. ATN: What about fluids? Are there increased needs in HIV disease? KW: If a person is having fevers or diarrhea, they're going to be losing a lot of fluid. It's very important that you replace electrolytes [as well as the water]. People can die from electrolyte imbalance -- sodium, potassium, chloride especially. The infant formula Pedialite is one option, but it is expensive and heavy to carry. We were recommending Gatorade, because that does have electrolyte replacement, but it can be expensive if you're drinking a lot, and it has sugar which could exacerbate the diarrhea. People say, why not just drink water? But that will wash out even more of the acid and electrolytes in the stomach, leading to further metabolic imbalances. A while ago our pharmacy obtained oral rehydration salts from the World Health Organization. The formula is pretty bland; you can taste a little salt. I believe it would be good to add that to the water, then dilute your nectars or other juices you may be drinking to replace your electrolytes. It comes in little packets for about 50 cents. Hopefully we'll see people using more of this. [Note: For information on how to obtain rehydration salts, see the resource section at the end of this interview.] Food Advice; Deficiencies ATN: Any general dietary advice? KW: Eat a more healthy diet -- including, for example, skinless chicken, and a variety of fresh fruits and vegetables. You need meat and other sources of protein. We do not advocate very restricted diets because it's hard to get the full protein, carbohydrate, fat, vitamins and so on that you need, with alternative diet therapy. It's difficult to say generically, "Eat more healthily," because you have to consider a person's individual lifestyle, how much money they have, where they're living, do they have a significant other who can shop and cook for them -- any number of things need to be considered. ATN: What about vitamin and mineral deficiencies? KW: Several micronutrient deficiencies have been identified in HIV disease: B-6, B-12, zinc, copper, selenium, thiamin and folate. Deficiencies may be because of intestinal damage from infections or illnesses; vitamin B-12 especially may not be absorbed. Selenium deficiencies may lead to cardiomyopathy. Zinc deficiency may contribute to anorexia and diarrhea, as well as altered immunity; conversely, zinc excess can further contribute to immune dysregulation. A study by Dr. Beach looked at people with some cognitive deficiencies and found that they were deficient in B-6 and B- 12 in particular. When they supplemented these back up to a normal level, the dysfunction cleared up. There are many possible reasons why a person's cognitive function is "not quite right" -- general malnutrition or even micronutrient deficiency might be the cause. However -- you don't want to automatically tell someone to take extra B-6 and B-12, without documenting serum levels of these vitamins. ATN: What about toxicities from overdoses of certain vitamins, especially fat-soluble vitamins (A, D, E, K)? KW: Fat-soluble vitamins not immediately needed by the body are stored in the liver. When probably over 60 percent of HIV patients have some form of liver disorder, and they are storing fat-soluble vitamins on top of that, it may exacerbate some liver-related problems. Other toxicities could be causing diarrhea, such as high-dose vitamin C or zinc, etc. Anemia, hair loss -- these could be caused by deficiencies, but they could also be caused by toxic levels of various micronutrients. Excessive amounts of vitamin C [can cause] a nutrient imbalance; particularly if taken with large doses of zinc, this can lead to copper depletion, which can further contribute to immune dysregulation. Unless people are familiar with these interactions it is important to get help from a qualified registered dietitian or physician to make educated decisions. We recommend, as part of an individualized therapy plan, to take one multivitamin a day. Often we recommend prenatal vitamins [because they include low or moderate doses of all the known vitamins, etc. that you need, whereas other multivitamins usually have some missing]. Some articles in the literature report taking 20 to 200 times the RDA of certain vitamins, etc. might be beneficial. More work needs to be done in this area; I would not recommend that you can take these treatments without concern. And in addition to the issues already discussed, taking megadoses can be expensive, and limited funds may be spent on supplements rather than on quality food. Whatever water- soluble vitamins your body can't use are flushed out through the kidneys... in other words, you end up with every expensive urine and little benefit from the megadosing. ATN: With HIV disease the body experiences hypermetabolism, which may cause nutrient needs to be different than the U.S. RDA. What guidance can you give people who can't access a dietitian? Is there something you can refer them to that explains these interactions? KW: That's a good question. The ADA Consumer Nutrition Hotline is available to you. (See below.) People can "guestimate" what their metabolic needs are for 24 hours with the following: calories: multiply 30-35 calories times your weight in kilograms; for protein needs, multiply 1.5 to 2.0 grams of protein times your weight in kilograms. These amounts will most likely help to maintain weight during relatively non-stressful times. If an opportunistic infection occurs, the body's needs may rise by 60%. Fever will raise the body's metabolism 7% for each degree Fahrenheit above normal. A registered dietitian can calculate your body's needs using an equation that takes into account your age, sex, height, and weight. This method also considers factors such as degree of illness and level of activity. Other Topics ATN: What about special "alternative" diets? KW: Some alternative therapy diets work for some people, but they may not have enough protein, carbohydrate, and fat. And they can be dangerous; for example, there's one that encourages you to eat moldy food to see if you're really sensitive to it. This could be even more detrimental to somebody who is immune compromised. ATN: What about Chinese herbal remedies, teas, etc. KW: I think there is something to a history of thousands of years of herbology -- and there are certainly conditions that western medicine cannot do a thing about, yet there may be some relief from non-traditional therapies. I do believe that HIV disease would benefit from a combination of eastern and western medicine. The concern I have is that people will go into a sports nutrition shop or health food store and buy whatever is recommended to them. People may spend a great deal of their money on supplements rather than quality foods. Here is where it is vitally important that people align themselves with a medical professional who can advise them on what to take. ATN: And antioxidants? KW: It's too early to have definitive answers. Antioxidants occur in foods. If you are already taking a multivitamin, you will be getting some that way, also. Examples of antioxidants are vitamins C and E, beta carotene, zinc, selenium. Antioxidants are said to neutralize free radicals in the body that contribute to immune dysfunction, aging, heart disease, and cancer. ATN: In choosing a multivitamin, what potency (dose) should you look for? KW: If your multivitamins are a bit more potent than the RDA, that won't hurt, as long as you are only taking one a day. When you do take your vitamins and minerals, take them with food. In order to be effective, vitamins, minerals, and trace metals need to chemically interact with food. ATN: What about exercise? KW: One of the simplest things we recommend is for folks to just walk and swing their arms. When watching TV, it's a simple matter to pick up soup cans or something like that -- or putting a two to five pound weight on your foot and lifting it. Low resistance, many repetitions, is the key so the movement doesn't exhaust you but does stimulate the muscles. ATN: Because if you don't use it, you'll lose it? KW: Yes, muscle tends to be exchanged for fat. We want to take a look at what impact exercise is going to have on the development and maintenance of lean body mass. Currently we don't have much data to go on. Dr. Hellerstein here is doing work with anabolic steroids. The problem with some of the steroids is that they may put some weight on you, but unless you are exercising it will be mostly fat, not lean body mass. But on the other side, people with HIV disease often fatigue easily, so you can't expect them to have a rigorous routine. ATN: What about differences between men and women? KW: In a Rhode Island study, the diagnosis of wasting syndrome was the second most common index diagnosis of AIDS in women. Moreover, women were greater than two and a half times more likely than gay men to have the diagnosis of wasting. To my knowledge, studies have not been conducted to determine whether the pattern of weight loss, i.e., muscle loss and fat preservation, is the same for women as it is for men. ATN: What can you bring to our readers about options, a note of optimism, things to think about? KW: The key again is to start working with people early in HIV disease, because we have a much better chance of keeping them nutritionally sound if we start earlier rather than later. We have also seen the possibility of moving someone from merely surviving, because they're so weak from malnutrition, to living a meaningful life due to optimal nutrition. We shouldn't give up hope; help is out there. I think the pervasive attitude is that weight loss and malnutrition are inevitable. You see that in both the health care provider and the client perspective. It is important for folks to hear that there is work being done in the field of nutrition and HIV disease. Moreover, creative and individualized approaches to symptoms which interfere with optimal nutrient intake can be successful. Nutritional Resources The following list of nutritional information was prepared in conjunction with the interview with Kristin Weaver, above. Upcoming Conference Third International Symposium on Nutrition and HIV/AIDS, Philadelphia, October 13-14. Organized by the Physicians Association for AIDS Care (see below), Philadelphia FIGHT (community-based research trials group), and the Pennsylvania AIDS Education and Training Center, this meeting includes many faculty members who are leading experts in the field. According to conference materials the symposium objectives are: "to disseminate the latest scientific information about the role of nutrition in the course of HIV disease and the prevention and treatment of AIDS-associated malnutrition; to improve the knowledge of those responsible for reimbursement decisions affecting nutritional strategies for insurance companies, managed care organizations, state Medicaid agencies, and Medicare administrators; to provide a forum to exchange information and to examine research, policy, management, and practice issues; and to improve communications between researchers and the users of research." Registration costs $75.00 and will be limited; organizers suggest registration by September 15th. For more information contact: Monica Patel, Philadelphia FIGHT, 201 North Broad St., 6th Floor, Philadelphia, PA, 19107, 215/557-8265. How to Get Rehydration Salts Oral rehydration salts based on the World Health Organization (WHO) formula are available in pharmacies and directly from Jianas Brothers, 2533 Southwest Blvd., Kansas City, MO 64108- 2395, 816/421-2880, fax 816/421-2883. The cost is about 50 cents per packet which dissolves in one liter of water. Food Safety and Nutrition Advice and Referrals CDC National AIDS Clearinghouse, 800/458-5231. Persons may request the free brochure "Eating Defensively. Food Safety Advice for Persons with AIDS." The materials prepared by the Food and Drug Administration for the general public are intended to help individuals lower the risk of food-borne illness. This includes information on how to avoid food poisoning, food handling and preparation, and tips for traveling abroad, shopping, and dining out. A fifteen minute video is also available for $12.00. Consumer Nutrition Hotline, 800/366-1655. Sponsored by the American Dietetic Association. Callers can speak with a registered dietitian, or ask for a referral to a registered dietitian. Referrals can be made to practitioners with specific specialties but callers need to know that the referral database contains only registered dietitians who have paid a fee to be included; it is not comprehensive. Clinics, hospital dietetic departments, public health departments, and AIDS service organizations may also be able to provide referrals. Diet counseling is not offered on the hotline, only general nutrition information. Meat and Poultry Hotline, 800/535-4555. This hotline, a service of the U.S. Department of Agriculture, is staffed by home economists and registered dietitians, Monday through Friday, 10:00 a.m. to 4:00 p.m., EST. Callers can get information about food safety. During other hours, a voice mail response system provides answers to commonly asked questions. Nutritional Counseling San Francisco Area: Bay Area Nutrition Counseling Center and Clinic, University of California San Francisco, San Francisco General Hospital. Patients are evaluated in-person by a physician and a dietitian at an initial visit and followed monthly thereafter. In addition to in- depth evaluation and counseling, clients receive a personalized manual outlining the results of laboratory and dietary assessments and the prescribed nutritional care plan, as well as extensive practical information. For more information or to schedule an appointment, contact Violet Garcia, patient liaison, 415/206- 8822. Illinois: The Cutting Edge. Under the direction of Cade Fields Gardner, RD (formerly Cade Fields Newman, RD), this organization provides education for professional dietitians and patients, nationwide referral, and direct patient care. The multidisciplinary approach emphasizes a healthcare team approach to treating individuals with HIV disease. This includes cooperative involvement by physicians, social workers, pharmacists, dentists, and other healthcare providers in a variety of settings. Services are available in several languages. Physician referral required. Contact: The Cutting Edge, P.O. Box 922, Carey, IL 60013, 708/516-2455, fax 708/516-2263. [Editor's note: These are two nutritional counseling centers that we contacted while writing this article. Many others could be listed as well.] Professional Organizations and Selected Resource Materials American Society for Parenteral and Enteral Nutrition (ASPEN). This is a multidisciplinary, professional, and scientific organization working to promote quality patient care, education, and research in the field of nutrition and metabolic support. Many peer-reviewed periodical and reference materials are available including Standards and Clinical Guidelines (for physicians, nurses, dietitians, and pharmacists). For a complete list of publications and programs contact: ASPEN, 8630 Fenton St., Suite 412, Silver Spring, MD 20910, 301/587-6315, fax 301/587-2365. Physicians Association for AIDS Care. In addition to their monthly journal, they have available Nutrition and HIV/AIDS: Proceedings of the 1992 International Symposium on Nutrition and HIV/AIDS, including the Nutritional Algorithm and the Nutritional Initiative of the Physicians Association for AIDS Care. This technical volume includes articles by some of the most respected experts in the field of nutrition and HIV, including Donald Kotler, Richard Beach, Cade Fields Newman, and Mark Hellerstein. Topics covered include nutrition and wasting, metabolic changes in HIV disease, and issues specific to developing countries. It also includes "An Overview of the PAAC Initiative," which presents strategies for coping with nutritional problems and an in-depth bibliography. ($25.00 including shipping and handling.) Contact: PAAC Publishing, Inc., 101 W. Grand Ave., Suite 200, Chicago, IL 60610, 312/222-1326, toll-free 800/243-3059, fax 312/222-0329. For less technical information, HIV Disease Nutrition Guidelines: Practical Steps for a Healthier Life presents practical information focusing on good nutrition, regular exercise, and stress management. Also included are recommendations for dealing with commonly occurring symptoms of HIV disease. It is published by the Physicians Association for AIDS Care with an educational grant from Stadtlanders Pharmacy. Free copies are available in English or Spanish from Stadtlanders Pharmacy, 800/238-7828. Bibliography and References Baum MK, Shor-Posner G, Bonvehi P, and others. Influence of HIV infection on vitamin status and requirements. Annals of the New York Academy of Sciences. September 30, 1992; volume 669, pages165-173, and discussion on pages 173-174. Beach RS, Mantero-Atienza E, Shor-Posner G, and others. Specific nutrient abnormalities in asymptomatic HIV-1 infection. AIDS. July 1992; volume 6, number 7, pages 701- 708. Beach RS, Morgan R, Wilkie F, and others. Plasma vitamin B12 level as a potential cofactor in studies of human immunodeficiency virus type1-related cognitive changes. Archives of Neurology. May 1992; volume 49, number 5, pages 501-506. Carpenter CC, Mayer KH, Fisher A, Desai MB, and Durand L Natural history of AIDS in Rhode Island. American Journal of Medicine. June 1989; volume 86, number 6 part 2, pages 771- 775. Chandra, RK. Micronutrients and immune functions: An overview. Annals of the New York Academy of Sciences. 1990; volume 587, pages 9-16. Chlebowski RT, Grosvenor MB, Bernhard NH, Morales LS, and Bulcavage LM. Nutritional status, gastrointestinal dysfunction, and survival in patients with AIDS. American Journal of Gastroenterology. October 1989; volume 84, number 10, pages 1288-1293. Grunfeld C and Feingold KR. Metabolic disturbances and wasting in the acquired immunodeficiency syndrome. New England Journal of Medicine. July 30, 1992; volume 327, number 5, pages 329-337. Kotler DP. Nutritional effects and support in the patient with acquired immunodeficiency syndrome. Journal of Nutrition. March 1992; volume 122, number 3 (supplement), pages 723-727. Kotler DP, Tierney AR, Wang J, and Pierson RN Jr. Magnitude of body-cell-mass depletion and the timing of death from wasting in AIDS. American Journal of Clinical Nutrition. September 5, 1989; volume 50, number 3, pages 444-447. Smith E and Orbolm M. Trends and patterns of opportunistic diseases in Danish AIDS patients, 1980-1990. Scandinavian Journal of Infectious Diseases. 1990; volume 22, number 6, pages 665-672. 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 fax: 415/255-4659 Internet: aidsnews.igc.apc.org Editor and Publisher: John S. James Reader Services and Business: 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 1994 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.