Date: Mon, 10 Jul 1995 21:39:48 -0700 (PDT) From: Tadd Tobias AIDS TREATMENT NEWS #226, July 7, 1995 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS Combination Antiretroviral Treatment: New Views, Evolving Practices Combination Treatment and Single Drugs: Interview with Margaret Poscher, M.D. Protease Inhibitor: Roche Lottery Deadline July 21 Wasting Syndrome -- Affordable Treatments Animal Cell Transplantation: FDA Meeting July 13 and 14 NAC Users: You Can Help NAC Research ***** Combination Antiretroviral Treatment: New Views, Evolving Practices by John S. James The interview with Dr. Margaret Poscher, below, is the first in a series of articles and interviews on combination anti- HIV treatment. For over a year, it has been almost a cliche that combination treatment is the wave of the future; however, the actual data on how well drug combinations work in people has been, and still remains, minimal and disappointing. But new information has recently renewed our interest in this potential advance: * Laboratory studies are showing that some combinations work much better -- or much worse -- than might have been predicted, in suppressing HIV in laboratory cultures. Some of these studies have been conducted over the last five years by Marty St. Clair, Ph.D., of Burroughs-Wellcome (now Glaxo Wellcome). Among the few drugs that she has tested so far, she has found that certain triple combinations work best. Some of the best results have been with AZT, plus either ddI or ddC, plus either 3TC or nevirapine. These laboratory studies have also suggested that it is better to combine drugs than to alternate them. Also, it is usually best to begin the different drugs at or close to the same time, if possible; the combinations may be less effective if the patient has already been using one of them for months or years, allowing resistance to develop. And the laboratory tests suggest that these combinations may be most active when the viral concentration is low, suggesting that they may work better in early stage HIV infection, than in late stage. Conditions in the human body, of course, are very different than in laboratory cultures. Therefore this laboratory work can only provide guidance or suggestions as to what combinations may be likely to work. Only human trials can tell whether or not a particular regimen is truly promising. Dr. St. Clair presented a preliminary report on this laboratory work last January at the 2nd National Conference on Human Retroviruses and Related Infections, in Washington, D.C. A full report will be published soon. * Recently we heard about a case of very successful use of one of the combinations suggested by the laboratory work (AZT plus 3TC plus ddC), by a person we know. His CD4 (T-helper) count was 300 a year ago, then declined rapidly to 110 last November 1, and to 70 last December 1, when he started the triple combination treatment. In February his count was 320, and in March it was 540. In April he had a bad case of flu, and his count dropped to 420. Then it went up to 450, and in June 1995 was 480. In November he had hairy leukoplakia, bad thrush, and bad scalp lesions; he had lost weight and was sleeping up to 18 to 20 hours a day. Now all symptoms are gone, and he has gained 25 pounds and is sleeping normally. He appears to be in perfect health. This person, importantly, was treatment naive when he started the triple combination. He used standard doses of the drugs, but sometimes reduced the AZT dose from 500 mg to 400 or 300, due to stomach upset. He was using no other treatment at the time except for acyclovir. Certainly no single case can prove that a treatment works; and we suspect that few people will find equally good results from this combination. But still cases like this compel attention, since comparable results are never seen with conventional HIV treatment. We mentioned this experience because it suggests a possibility, a goal, worth aiming for. Also, it suggests designs for clinical trials; for example, if a patient has a CD4 count below 50 and has CMV retinitis, and combination HIV therapy raises the CD4 count to a level where CMV is not normally a risk, will the retinitis stop progressing, thus reducing or eliminating the need for specific CMV treatment? * On June 30, Glaxo Wellcome applied to the FDA for accelerated approval for 3TC, for use in combination with AZT as first-line treatment for adults with CD4 counts under 500, and for children who meet the CDC guidelines for treatment with antiretrovirals. If the drug is approved for this indication, it will probably make combination treatment the standard of care for many (though not all) persons under 500, making it much easier to get this treatment paid for. It will also encourage experimentation with three-drug combinations, as approved drugs like ddI or ddC are added to the regimen. Today, combination antiretroviral treatment, especially triple combinations, are more talked about than used. As we asked around for referrals to physicians who might have experience with triple combinations, the same names kept coming up again and again. Most of them have only used triple combinations with a few patients. And they have different approaches to when and how they use these treatments; consensus has not yet developed. This slow start for combination treatment is not surprising, due to the lack of definitive data from clinical trials. The interviews in this series will examine some of the different approaches which are in use, and why physicians make the choices they do. Note that these interviews will focus primarily but not only on combination treatment; they will also look at related medical topics when they arise. ***** Combination Treatment and Single Drugs: Interview with Margaret Poscher, M.D. by John S. James Margaret Poscher, M.D., is an internist in private practice with Quest, a five-physician medical group in San Francisco. Dr. Poscher is also Assistant Clinical Professor, University of California Medical Center, and Director of HIV Clinical Services, University of California Mt. Zion. ATN: Which antiretroviral combinations do you most use or prefer? Dr. Poscher: I am disappointed that there is still not much published information on combination therapy. I was on the fence about combinations for a number of years. But in the last two years, and especially with viral load assays now available, it has become clear that combination treatment is incredibly important. I don't think I have any patients on monotherapy, except for some on d4T. My favorite combination now is AZT plus 3TC. I foresee that as being initial therapy, when 3TC is approved; patients who have CD4 (T-helper cell) counts below 500, or have a certain threshold level of HIV RNA, will be started immediately on this combination. At this point, with patients who are asymptomatic and have a relatively high CD4 count, and a moderate viral load, between 10,000 and 100,000 copies of RNA, I am starting those patients on AZT plus ddI, or AZT plus ddC. They make the decision of ddC or ddI, based on my description of the two drugs. I tend to prefer ddI, as I have not been impressed with ddC as an antiviral. This week I had a patient who recently seroconverted, and in a big way -- with several million copies of HIV RNA, a big dip in his CD4 count, and who continues to have over 100,000 copies of RNA. In 1995 there is concern about people becoming infected with AZT-resistant virus. So we discussed potentially starting him on d4T as initial therapy, and using d4T with either ddI or 3TC. I think that d4T with ddI is a very good combination, especially in people with higher T- cells, who tend not to get neuropathy as easily as advanced patients. In patients I've had on AZT plus 3TC who have developed complications -- especially anemia, the big complication I have seen, especially in patients with more advanced disease -- I've had success switching them to d4T plus 3TC. Occasionally I will use the triple combination AZT plus 3TC plus ddI; this is based on Dr. St. Clair's report at the 2nd National Conference on Human Retroviruses and Related Infections (January 29 - February 2, 1995, in Washington, D.C.) on laboratory studies with this combination. Since then there has been a question raised about possible antagonism between ddI and 3TC, but this is not yet substantiated. With these untested combinations, we do have to be careful about unknown potential antagonisms. ATN: Any other thoughts about which patients are the best candidates for which treatments? Dr. Poscher: It is probably also important to look at the viral load. People with very high levels of HIV RNA, I would be more likely to put on a triple combination. Some patients may want to start therapy very early; they may only have 15 or 20 thousand copies of RNA, and CD4 counts of 500 or above; you might even consider monotherapy for somebody like that. Or I might put them on AZT plus ddC, as ddC is easier to take that ddI. With high viral loads, I would dose higher, and give more drugs, at least initially, until the viral load drops. ATN: On doses, do you tend toward the lower end of the standard range? Dr. Poscher: I tend to give low doses. For AZT, I give 300 or 400 mg per day total. With ddC, I refuse to use the 0.75 mg tablet; my experiences with ddC back when it was in parallel track was that higher doses just meant more neuropathy and more anemia when used with AZT. So I tend to stick to 0.375 mg of ddC three times a day. With ddI I also use low doses, because of problems with pancreatitis which I saw when the drug was parallel track; my cohort of patients had close to a 20 percent incidence of pancreatitis. But that is when we were using total daily doses of 750 to 900 mg. Now I tend to give 250 mg of ddI once per day. I was sad to see the 375 mg sachet taken away, because I had many patients on 375 mg once per day. I dose it once a day for convenience for the patient; most patients cannot find two times in a day when they have an empty stomach, since usually they are trying to eat as much as they can to maintain their weight. To try to fast for an hour to be able to take ddI twice a day usually means missing a meal, at one end of the day or other. So I encourage them to take it in the middle of the night, if they wake up to urinate, as they often do. If you make it easy for people, they are more likely to take the drug; it is better for them to get one good dose in than skip it altogether because it's inconvenient. ATN: What differences do you see with therapy naive patients, vs. those who have been on AZT for a long time? Dr. Poscher: It's like night and day; it is significantly different. I think 3TC is the one exception, where you can add it to AZT and still get some mileage out of the AZT. I have completely given up on adding either ddI or ddC to a patient who is already on AZT; I think that is a waste of time. When you start a naive patient on antiretroviral treatment early on, that is where those two drugs have a role -- but not in somebody who has been on AZT for three or four years. The only drugs I could see adding then would be 3TC, or potentially a protease inhibitor if that were available. For patients who are on AZT and not eligible for 3TC today because they have a CD4 count over 100, I usually switch them to d4T, usually to a combination of d4T and ddI. ATN: Do you switch them all at once to the combination, or do you start one drug first? Dr. Poscher: All at once. Some patients are hesitant; they want to try one drug and start at a low dose and get used to it. But I encourage people to go for it, take both drugs full dose from day one. Acyclovir ATN: What about other antivirals, such as acyclovir, or oral ganciclovir prophylaxis? Dr. Poscher: I'm pro acyclovir -- absolutely for people who have a known history of herpes, or zoster. I have all of them on suppressive doses of acyclovir, 400 mg twice daily. A few patients don't want to take it; they are usually patients who have never had herpes or zoster outbreaks. Still I encourage them to consider it, as I think there are other herpes viruses which are not clinically apparent which are exerting some effect. And acyclovir is safe; there is no major drawback to using it. In the six years I have been in private practice, I have seen two cases of acyclovir-resistant herpes, after treating many people with acyclovir. Oral Ganciclovir Oral ganciclovir for CMV prophylaxis, I am still ambivalent about. I am concerned about the potential for resistance; I think it is far more likely with ganciclovir and CMV, than with acyclovir and herpes. I have had a couple patients who have been on protocols for oral ganciclovir prophylaxis and have then developed CMV, and it has been a nightmare. One patient was resistant to everything; oral ganciclovir led to ganciclovir resistance, and before he saw foscarnet he was foscarnet resistant, and he was also resistant to HPMPC. My thinking now is that there are better therapies coming for CMV, such as local therapies through injection or eye implants. With these we have a better chance of conserving retina, which I think is the important thing, than through years of treatment with oral ganciclovir and its complications. So I am leaning to not using oral ganciclovir in patients who have no CMV whatsoever, and to be careful with ophthalmologic followup -- frequent eye exams, and alerting people to symptoms of CMV retinitis. I would use oral ganciclovir in patients who had end-organ CMV disease -- CMV esophagitis, colitis, gastritis -- but have not yet developed retinitis. Here you might use oral therapy as secondary prophylaxis essentially -- as those patients will probably develop retinitis within six to 12 months. For treatment of CMV retinitis, people often do well with oral ganciclovir, after an initial course of IV induction treatment. I have had a couple patients recently who have gone one year without a recurrence, on oral ganciclovir. Other, Miscellaneous Potential HIV Treatments ATN: Are there other therapies that many of your patients are on, such as experimental immune modulators? Dr. Poscher: I have probably a dozen who continue to use DNCB. Many continue to be on the TP-5 protocol. A few are interested in the Cytolin, a mouse monoclonal antibody; I have not seen enough on that to form an opinion. I think the enthusiasm for IL-2 has diminished; nobody has asked about it in months. Thalidomide is the newest. I used it several times over the past several years, in patients with oral aphthous ulcers, and found it to be a very easy drug to take. The patients I had who were maintained on thalidomide seemed to do very well; I used to wonder if maybe the thalidomide was doing something for them [vs. HIV disease, not only vs. the ulcers]. So I'm encouraged that we at least have access to it now, as a potential treatment for wasting, and possibly for MAC, since it has been used in the treatment of leprosy for decades now. [See "Thalidomide and HIV: Several Possible Uses," by Denny Smith, AIDS TREATMENT NEWS #221, April 21, 1995.] ATN: What kinds of changes are you seeing in CD4 and viral load with the different combination therapies? Dr. Poscher: One therapy naive patient had avoided starting antiretroviral therapy for years, and his CD4 count kept going down. Finally I insisted that he do the HIV RNA test. His count was greater than 1,600,000. He decided to go into a clinical trial of PMEA; when he finally started that treatment, his viral load was still over a million, and his CD4 count had dropped below 200. He was a perfect example of an antiretroviral naive patient who was put on the mid dose of PMEA, and his viral load went from over a million to 30,000, and his CD4 count went from less than 200 to over 500, after six weeks on PMEA. He is now on AZT plus 3TC, and doing very well. I have seen at least one log (ten fold) viral load reductions with d4T and 3TC. And when the RNA goes down, the CD4 count goes up. Usually it does not last -- but I find that people often reach a new plateau. They get a big increase, and then it comes down a little, and they stay at that new plateau, a little higher than they originally were, for a good six months, or longer in some cases. I've seen people go from well over 100,000 copies of HIV RNA, to under 10,000 copies. [Part II of this interview will look at possible side effects of combination treatment, treating a sudden CD4 drop, and reimbursement and managed-care issues.] ***** Protease Inhibitor: Roche Lottery Deadline July 21 In a widely distributed June 21 press release, Hoffmann-La Roche announced details of "The Invirase* International Compassionate Treatment Program." This program will distribute saquinavir (brand name, Invirase), a protease inhibitor, to persons with a CD4 (T-helper) count under 300 who no longer benefit from approved antiretroviral drugs (AZT, ddI, ddC, and d4T), and meet other entry criteria. Roche not only allows, but even encourages, combination use of its protease inhibitor together with the approved antiretrovirals. 60 percent of the slots will be reserved for persons with a T-helper count under 50. [Note: Roche uses the spelling "proteinase," instead of "protease." The meaning is the same.] The drug will be made available to 2,280 patients in the U.S., 96 in Canada, and about 1700 in Europe and Australia; Roche has set up a lottery in case more people apply for the drug. To get into the first U.S. lottery drawing, your physician must enter you on or before July 21, 1995. (When more drug is available, another lottery will be conducted, including those not selected from the first lottery, and others who apply later. Therefore, if you miss this deadline, you can still apply for a possible subsequent lottery.) To get details about this program, you or your physician can call 800/332-2144, Monday through Friday between 9:00 a.m. and 8:00 p.m. Eastern time. You can also request information by fax, 800/332-7644; or by mail, by sending a written request for information to the Roche Data Coordinating Center, P.O. Box 81312, Wellesley Hills, MA 02181. [In Canada, the program is slightly different; call 800/257-3741 for Canadian information.] Comment We have not been greatly impressed by the previous data we have seen on saquinavir, at the doses which will be used in this program. The drug seems to be safe, and to be effective; but the average size of the effect is not that great, unless larger doses are used. However, some individuals do seem to benefit much better than the average. And new data from Roche (see below) may make saquinavir a better drug, by showing doctors how to use it more effectively. It is too early to judge this drug. There have been concerns that people who use saquinavir alone are likely to develop resistance to it, which may cause cross-resistance to other protease inhibitors. If this happens, it could mean that people who use an early protease inhibitor might lose the ability to benefit not only from that drug, but also from better protease inhibitors which may be available in the future. This issue has been controversial among experts; for example, Roche's experts and Merck's experts have disagreed about it. Now Roche claims that new data, to be released July 10 at the Fourth HIV Drug Resistance Workshop in Sardinia, Italy -- data on almost 100 people, compared to the four to six people that Merck tested -- indicates that saquinavir does not cause resistance to other protease inhibitors -- and that the development of resistance to saquinavir itself can be reduced by using that drug in combination with AZT. Over the next few weeks, we will see how this new information is evaluated by the medical community, and by scientists independent of both companies. It is also important to realize that different people have very different individual responses to AIDS treatments. For some people, this drug works much better than it does on the average. One argument in favor of trying saquinavir is to see if it works exceptionally well for you. What if you cannot decide whether or not to apply for the lottery program, and cannot get an appointment with your doctor before the deadline? One strategy is to call and ask your doctor to apply anyway -- it is easy for the doctor to do, requiring only a simple form and a copy of a T-cell test from your medical records. Everything can be handled by fax. Also, you can start the whole process on your own, by calling the phone number above to get information about the program, and advice on getting your doctor to enter you. Later, if you are accepted, there will still be some time before you actually get the saquinavir; and you can use this time to meet with your doctor decide whether or not you want to use the drug. We will be surprised if Roche gets 2280 U.S. applicants for this lottery by July 21. There just isn't enough time for the word to get around, for over 2,000 people to hear about the program, grasp the information, see if they qualify, decide if they want the drug at all, make doctors appointments, talk with their physicians, and get the forms turned around, all between the first detailed press release on June 21, and the lottery cutoff on July 21. On July 5 Roche told us that they were optimistic on filling the program, as they had 5,000 phone calls after articles were published in The Wall Street Journal and other newspapers; and they had several hundred completed applications as of July 3. Even so, we still doubt that they will get 2280 qualified applications by July 21. If they do not, this means that no lottery will be needed, since all qualified applicants who apply by that deadline will get into the program. And there may also be extra slots for people who apply after July 21; however, we are not sure about this. But on the negative side, failure to fill the lottery in one month might be wrongly interpreted as lack of public interest in expanded access, protease inhibitors, or new AIDS treatments, when in fact the obvious obstacles listed above would be responsible. We believe that the expected inability to fill all slots immediately could have been predicted even before the program was announced. Even under the best circumstances it is hard to inform the public and get people to change their behavior. This program has to get over 2,000 specially qualified patients and doctors to change their behavior together, to follow a new procedure to get an experimental drug that even the doctors do not know much about, all within one month after receiving a form letter or reading an article in a newspaper. [Note: There is also a completely separate program for access to the Merck protease inhibitor best known as MK-639 (it has now been given the chemical name indinavir sulfate, and the brand name Crixivan*); many third-party observers consider this a more promising drug than low-dose saquinavir. The Merck program, which will begin in August or September, will provide MK-639 to 1400 people who have a CD4 count below 50 and meet other entry criteria. Information about this program will be announced by Merck, probably in July.] ***** Wasting Syndrome -- Affordable Treatments by John S. James The May issue of Treatment Issues, published by GMHC (the Gay Men's Health Crisis, in New York), includes several excellent articles on treatment of wasting syndrome -- severe loss of lean body mass not due to obvious causes such as nutritional deficiency or intestinal infection -- in AIDS. The bottom line is that there are inexpensive potential treatments, and some early experience suggests that most patients can be successfully treated by using one or another of them. This may mean that only a few patients will need the extremely expensive treatments, which are out of reach economically for most people -- human growth hormone, which costs about $1000 per week, or total parenteral nutrition (TPN), which usually costs even more. [Note: While human growth hormone costs about $1000 per week, the growth hormone for cows (which will not work in humans) costs $3 per week. Both are made by similar recombinant technology; we have been told that the amino acid sequences are two-thirds identical. But for people the commercial price is $42 per milligram (somewhat less for "cost recovery" for a special AIDS program, where the drug has not been fully approved). For the closely related agricultural product, however, the price to dairy farmers, we have heard, is less than 2 cents per milligram. Someone should investigate how the price of human growth hormone has remained so disproportionate to the cost of production for many years. A number of companies sell this drug throughout the world -- at the identical price of $42 per mg. The substance itself is produced by the body and cannot be effectively patented; processes for manufacturing it are patented, and there has been considerable patent litigation.] [Persons who need human growth hormone and cannot pay for it should realize that there is an indigent program, sponsored by Serono Laboratories, Inc., the company which researched the use of human growth hormone for AIDS-related wasting. Serono provides the hormone without charge to a small number of patients who need it and have no way to pay.] An example of an affordable treatment for AIDS-related weight loss (when not too severe) is testosterone enanthate, used with an appropriate exercise program. In some cases nandrolone, an anabolic steroid, is added as part of the regimen. While this treatment has not been proven in clinical trials, some leading AIDS physicians are using it and finding good results; Treatment Issues mentioned Marcus Conant in San Francisco. "We are frequently using testosterone to treat people with AIDS-related weight loss," Dr. Conant told AIDS TREATMENT NEWS. "And in some cases we are also using nandrolone when these people have shown some promise of weight gain." Dr. Conant explained that the nandrolone generally worked well only in those who had already responded successfully to the testosterone. What about people with true wasting -- who have lost more than ten percent of their body weight, and continue to lose weight despite testosterone, exercise, and nandrolone? Dr. Conant's team has found that these people respond very well to human growth hormone; 14 of the 16 severely wasting patients they have treated have gained weight with the hormone, according to Gordon Sanford, PA-C, a physician's assistant in Dr. Conant's office. And they have not found any other treatment which worked for those patients -- the FDA- approved wasting treatments Megace or Marinol did not work. [However, Conant's experience cannot rule out thalidomide, or ketotifen (see below). Thalidomide has seemed to work for severe AIDS-related wasting in small studies; larger trials are needed to confirm this finding. Ketotifen has led to striking weight gain in a few cases; it needs a formal study.] Your physician can call Dr. Conant's office in San Francisco, and talk to Dr. Conant, or to Gordon Sanford, to learn the doses, and other critical details and important information on how to use testosterone treatment most effectively. [Note that this discussion of testosterone, and the other potential wasting treatments below, assumes that the patient has already had a complete workup to look for any obvious causes of weight loss, such as parasites or other intestinal disease, MAC or certain other infections, lymphoma, inadequate food intake, etc. These specific causes need to be considered first. The potential weight loss/wasting treatments mentioned here are tried when such specific causes cannot be found.] Another affordable possibility for treating wasting syndrome is ketotifen, believed to be a very safe drug, which is widely used in Europe for asthma and allergies, but not approved in the U.S. You can get ketotifen through the PWA Health Group in New York (phone 212/255-0520). The main drawback is that not much research has been done yet on using it for AIDS-related wasting; also, since the drug is not regularly used in the U.S., most doctors here will not know anything about it. The main advantage is that there seems to be little risk, cost, or other "down side" to trying it. A third affordable possibility is thalidomide, which is now available under a special, tightly controlled "underground compassionate access" program through the PWA Health Group, or through Healing Alternatives, a similar buyers' club in San Francisco. (Thalidomide is also available through an official, FDA-approved compassionate access program for people with AIDS, but at this date that is only for treatment of aphthous ulcers, not for treatment of wasting.) The main danger, of course, is birth defects if this drug is taken in pregnancy. In addition, larger doses of thalidomide can cause neuropathy or other adverse effects. Two treatment are FDA-approved for AIDS-related wasting syndrome: megestrol acetate (Megace), and also dronabinol (Marinol), which uses the active ingredient of marijuana as an appetite stimulant. Both of these are expensive; and it is controversial how effective they are for increasing lean body mass, which is what a wasting-syndrome treatment must do. The May Treatment Issues mentions these treatments, but does not discuss them in depth. (We have been told by others that persons who use Megace should have their testosterone levels monitored.) [Note: on July 4 we talked to Dave Gilden, editor of Treatment Issues and author of an article on human growth hormone in the May 1995 issue. He said that if he were publishing that issue today, it would have more information on exercise, and more coverage of Megace and Marinol. Also, he would urge activists to campaign to get the FDA-approved compassionate access program for thalidomide expanded to allow persons with wasting syndrome -- not only those with aphthous ulcers, as is the case today -- to receive the drug. And he would emphasize the great need for more research in AIDS-related wasting.] We strongly recommend that anyone interested in wasting syndrome get the May 1995 Treatment Issues; it includes background and details which we only summarized above. Better yet, anyone interested in AIDS treatment can get a complete set of the back issues of this very useful publication for a suggested donation of $25. To order, send $3 for the May issue only, or $25 for a reprint of all the back issues, to: GMHC, Treatment Education, 129 West 20th St., New York, NY 10011. We also recommend subscribing to Treatment Issues, suggested donation $35/year (11 issues) for individuals, $70/year for physicians, institutions, or international subscriptions. [Note: For additional information on wasting and its treatments, also see "Turning the Corner on Wasting? A Symposium on Wasting Disorders," by Jeff Getty, in BETA (Bulletin of Experimental Treatments for AIDS), June 1995; BETA is published by the San Francisco AIDS Foundation. And see Notes from the Underground, April/May 1995, available without charge from the PWA Health Group, 212/255-0520.] ***** Animal Cell Transplantation: FDA Meeting July 13 and 14 by John S. James Advances in organ and cell transplantation, and in basic immunology, have now raised the possibility of transplantation of organs or cells from animals to humans. For example, it is known that immune cells in baboons are resistant to HIV infection. If these cells could survive transplantation to humans, and could work properly in humans, they might conceivably provide immunological resistance to HIV, like human cells do -- except that the baboon cells could not be destroyed by the virus. If it works -- still a big if -- such a procedure might allow the reconstitution of an immune system in persons with late-stage AIDS. The reverse -- transplantation of human immune cells to a baboon -- has already been done. So far the cells have survived, and tests indicate that proliferation responses are functional, according to treatment activists who have followed this work closely. The first test of baboon to human cell transplantation was scheduled to have been tried already; the principal investigators are transplantation specialists at the School of Medicine of the University of Pittsburgh, and AIDS specialists at the University of California San Francisco Medical Center. Under the Federal regulations which were in effect until recently, such a test only needed to be approved by a local IRB (institutional review board). It did not need additional approval by the FDA -- just like a surgeon does not need FDA approval to try a new, experimental operation. But shortly before the first baboon to human transplant was to be done, the FDA expanded its authority into this new area, and told the researchers that they would have to get FDA approval first. The researchers complied, postponing the trial and applying for FDA approval. However, animal to human transplantation involves major issues which must be considered -- including the theoretical risk of transmitting an animal disease to humans, conceivably even causing an epidemic. But this risk must be seen in perspective. Animal to human transplants have been attempted several times in the last 25 years, with some long-term engraftment; so far no dangerous animal diseases have been transmitted. And tens of thousands of people die every year because of lack of human organs to transplant. Some experts believe that there should be more animal trials first, before attempts to transplant animal tissues into humans. But others fear that such trials will take years to finance, organize, and conduct, and cannot be definitive anyway. Sorting out all these heavy policy issues might take a long time, seriously delaying an early proof-of-concept trial. The requirement for advance FDA approval could well mean, in practice, that the very difficult general policy issues for the whole field of "xenogeneic" (animal to human) organ and cell transplantation will have to be considered first -- before even the earliest proof-of-concept human trials can go forward. A bureaucracy usually prefers to delay making decisions in a completely new area, until it has a policy in place. If that happens in this case, it could disastrously delay the research. The alternative is to allow the small, early research to begin, even while the overall policy is being worked out. These matters will be considered at a critical FDA meeting on July 13 and 14, at the Holiday Inn in Bethesda, Maryland. This meeting is open to the public. David Hook, of the Xenogeneic Committee of ACT UP/Golden Gate in San Francisco, told AIDS TREATMENT NEWS that people should call the FDA's Office of AIDS and Special Health Issues, 301/443-0104, to tell the FDA that the baboon transplantation trial should go forward without delay. For more information, including on how you can be involved, leave a message for David Hook on the voicemail of ACT UP/Golden Gate, 415/252-9200. Comment Until now most of the AIDS community has known little about this issue, which has been brewing quietly behind the scenes for about two years. Those involved preferred not to seek publicity until recently, when the research was threatened with long delays. But now the activists and researchers who want to move this research forward do need public support. This situation presents a challenge to the AIDS community. We must get up to speed quickly in this complex and difficult area; otherwise, decisions seriously harmful to people with AIDS are likely not only to be made, but also to become institutionalized. [Note: This preliminary article is based on interviews with treatment activists, and on published information. Due to time constraints, we did not interview the researchers.] ***** NAC Users: You Can Help NAC Research If you have used NAC (N-acetylcysteine) for at least three months, you could help a scientific study at Stanford University by completing the survey below. This survey is to tell the researchers why you are using the treatment -- and what effects you have seen, good or bad. NAC has long been one of the most popular treatments sold in buyers' clubs; it is also sold in health-food stores. The Stanford study, which started over a year ago, has given NAC or placebo to about 60 volunteers (mostly recruited in San Francisco), in a double-blind trial (meaning that neither the volunteers, nor their doctors, nor the researchers themselves, know who is getting the real drug and who is getting the placebo). Now the researchers are about to break the blind (learn who got the real drug) and analyze the study statistically. But first, they must formulate all the questions they want to ask of the data; for scientific reasons, it is important that they do this before they break the blind. The survey below is to give them ideas of any questions they should be asking, but may have overlooked; this survey by itself is not intended to be scientific or statistically valid by itself, but to help formulate questions for the analysis of the clinical trial, to make the trial itself as useful as possible. The researchers are especially interested in any changes in energy, in sexuality, or in neurological symptoms -- or any other observations which they may have not thought about, but which might have changed when you started the treatment. We encourage you to copy this article so that friends who have taken NAC can also participate. The Survey For persons who have taken NAC for a total of three months or longer, please answer the following questions on a separate sheet of paper, and send your reply to the address below. Please answer each question separately, using the question number so that the researchers know for sure which response is to which question. (1) Approximately how long have you taken NAC? (If you have discontinued, or stopped and started again, let us know.) (2) What is your usual single dose? How many times a day do you take this dose? (3) What brand of NAC do you use? (4) What benefits do you think you may have had from NAC? Please classify each possible benefit as "pretty sure" if you are pretty sure it is due to NAC, or "probably" if you think that it is probably due to NAC. (5) Have you had any serious side effects which may be due to NAC? You can also answer the following questions if you wish: (6) How long have you known you were HIV positive? (7) What were your last CD4 (T-helper) and CD8 counts when you started taking NAC? Also, what were your most recent CD4 and CD8 counts? And how long ago were they measured? (8) Have you had AIDS-defining opportunistic infections? If so, which ones, and when were they diagnosed? (9) If you are no longer taking NAC, why did you discontinue it? Also, have you had any AIDS-defining opportunistic infections since you stopped taking NAC? If so, when? (10) Please add any additional comments you wish to make. (11) Optional: If you would be willing to answer any further questions the researchers may have, or if you wish to receive a summary of the survey responses, include your name and address. (On the other hand, you may reply anonymously if you wish.) Please send your answers to: Stanford NAC Project, c/o Davies Medical Center, Castro and Duboce Streets, San Francisco, CA 94114. ***** 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@aidsnews.org Editor and Publisher: John S. James Reader Services and Business: Richard Copeland Thom Fontaine Tadd Tobias Denny Smith 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 1995 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.