AIDS TREATMENT NEWS Issue #184, October 1, 1993 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: L-524: New Protease Trial Recruiting AIDS Treatment Strategies: Interview With Lisa Capaldini M.D. Clinton Health Care Plan: Major Improvement, Issues Remain Alternative Treatment Library Available Hypericin: Oral Trial Planned Announcements Advanced KS: Liposomal Doxorubicin Trial Recruiting, Many Cities San Francisco: NAC Trial Recruiting Help Wanted: AIDS Treatment Specialist, Atlanta Spanish Treatment Information: Boletin de Tratamientos Experimentales para el SIDA Minneapolis: Skills Building Conference on Influencing HIV/AIDS Policy, October 12 8 California Legislation: Breast Cancer Good News; Others,Calls, Faxes by October 10th 8 In Memoriam: Jesse Dobson 8 ***** L-524: New Protease Trial Recruiting A new protease inhibitor developed by Merck Research Laboratories is beginning its first phase II trial, which will take place at three East Coast sites. L-524 (L-735,524) has been in small human trials since February 1993. In laboratory tests, it gives 95 percent inhibition of HIV spread in cell cultures at concentrations of 50 to 100 nanomolar (0.05 to 0.1 micromolar). In people, anecdotal findings have shown about a 50 percent reduction in p24 antigen (comparable to AZT), with no viral resistance found so far. But since only a handful of people have taken L-524 for more than two weeks, all that can be concluded now is that more trials are justified. P24 antigen changes normally happen very quickly; the big question is whether they are sustained. The new phase II trial will last six weeks, and may be extended. It will randomly assign volunteers to three groups: L-524, 200 mg every six hours; L-524, 400 mg every six hours; and AZT, 200 mg every eight hours. No toxicities have yet been found from L-524 in the 400 mg dose; however, some volunteers given a higher dose (600 mg every four hours) showed rises in liver-function tests. Volunteers must by 18-65 years old, with T-helper count below 500 (there is no lower limit). They must not be pregnant. Creatinine must be less than 1.5 times upper limit of normal, and liver transaminases and bilirubin less than 2 times upper limit of normal. Volunteers cannot have previously used any protease inhibitor. They will be tested and need to have a positive p24 antigen (at least 25 pg/ml). Before entering the trial, they will need a 30-day washout of other investigational drugs, and a two-week washout of AZT, ddI, and ddC. For more information, contact the study coordinator at one of the three trial sites: * Pitt Treatment Evaluation Unit, University of Pittsburgh, contact Nancy Mantz, R.N., 412/647-8125. * AIDS Treatment and Evaluation Unit, University Hospital, State University of New York at Stony Brook, contact Ruth Ann Burk, R.N., 516/444-1658. * Bellevue Hospital Clinical Research Unit, New York University, New York City, contact Mary Ann Kiernan, R.N., 212/263-6565. Comment Protease inhibitors are generally considered the most promising class of experimental drugs at this time; they are being developed by a number of companies. Unlike other classes of anti-HIV drugs, protease inhibitors are able to completely shut off viral replication in laboratory tests. And because the protease is a small enzyme, it should offer few opportunities for the virus to mutate and develop drug resistance. The major problem with protease inhibitors has been getting them into the body and to the sites where they are needed. The p24 antigen reduction seen in a few patients so far suggests that this drug is bioavailable. Similar results have been seen with a similar protease inhibitor being developed by Hoffmann-La Roche. The fact that the p24 antigen result is only comparable to that of AZT does not necessarily mean that the drug will only work as well. With protease inhibitors, new virus continues to be produced by already-infected cells; however, this virus is immature and not infectious. The p24 antigen test may be detecting this defective virus, and therefore not giving a true picture of how well this class of drug is working. ***** AIDS Treatment Strategies: Interview With Lisa Capaldini, M.D. by Denny Smith Several years ago, AIDS TREATMENT NEWS decided to seek out the experiences of physicians who had been treating HIV long enough and intensively enough that their opinions might be especially valuable for people living with HIV or AIDS, as well as for researchers and other physicians. Lisa Capaldini, M.D., General Internal Medicine, was the first physician we interviewed (see AIDS TREATMENT NEWS issue # 100, April 6, 1990). Dr. Capaldini continues to treat many patients with HIV, and to teach HIV care as an Assistant Professor of Medicine at the University of California San Francisco. We asked Dr. Capaldini again to share her experiences treating symptomatic HIV disease -- especially what she has learned in her practice and believes should be more widely known. Opportunistic Infection Prophylaxis DS: Everyone knows to prophylax against Pneumocystis pneumonia, but beyond that, there isn't a solid consensus. When do you initiate the different prophylaxes, and what do you use? LC: I try to have a structured routine with my HIV patients; those with very low CD4 [T-helper cell] counts (less than 50- 100) get regular eye checks, MAC prophylaxis and of course, PCP prophylaxis. I think AZT can actually be used as a prophylactic measure, in that it seems to help prevent dementia. [AZT, unlike many drugs, is known to cross the blood/brain barrier.] AZT also seems to reduce the incidence of HIV enteropathy, which can cause serious diarrhea and weight loss. For MAC prophylaxis, you can make a good argument for single- drug therapy, with either rifabutin, clarithromycin, or azithromycin when CD4 counts fall below 100. I have been using clarithromycin, 1000 mg a day for people who can tolerate it. It's important not to combine this with Seldane, which can lead to a cardiac rhythm complication called prolonged QT syndrome. A good thing about clarithromycin is that it may also prevent some of the respiratory infections that people with HIV are prone to, like pneumococcus, and haemophilus, and staphylococcus. The cousin of clarithromycin, azithromycin, is probably just as good. If rifabutin is used, it's important to explain to patients that their body fluids, especially urine, will turn orange. But none of these drugs can be expected to control MAC indefinitely. I think that detecting early, even asymptomatic, CMV disease is really important. By the time CMV causes an identifiable retinitis, it is already a disseminated infection, capable of causing fevers and wasting. People with CD4 cells less than 200 should have their eyes checked every three months, and if the CD4s drop below 100, then every two months. If you catch CMV disease early, you may prevent some of the constitutional symptoms associated with a disseminated infection; if you notice visual symptoms but wait to treat them, you may compromise someone's vision, as anti-CMV therapy does not fully reverse visual symptoms. DS: Are you recommending anything for prophylaxis of fungal infections? LC: Yes, I'm suggesting that people with less than 200 CD4s take ketoconazole, fluconazole, or itraconazole, daily. We're seeing much less cryptococcal meningitis than we used to, probably because so many people have already been taking one of these drugs for Candida infections. Even though ketoconazole does not cross the blood-brain barrier, I believe it can prevent CNS fungal disease by decreasing extra-CNS fungal burden. Fluconazole does cross the blood- brain barrier, but is much more expensive. In my experience, it is rare for someone taking daily ketoconazole prophylaxis to develop cryptococcal meningitis. With ketoconazole, it's important to take the drug on an acidic stomach, so I tell people to take it with an acidic beverage, like orange juice, coffee or a cola. This is especially important if they are also on an acid-lowering drug like cimetidine or ranitidine. Another precaution about ketoconazole is that, rarely, it can interfere with androgen binding and androgen receptors, which can cause a situation that's clinically indistinguishable from androgen or adrenal hormone deficiency. On the other hand, there is a danger in overdoing preventive medicine in not individualizing recommendations, and scaring people. I try to streamline my prophylaxis recommendations for my patients, so they don't feel like they're a carton of eggs and one little misstep will mean disaster. Psychologically that can wear people out. I am seeing more and more people with lower and lower CD4 cells who do not have any opportunistic infections and whose overall health is quite good. Cervical and Anal Cancer DS: The incidence of cervical and anal cancer has been reported at the last two International Conferences on AIDS to be increased in people with HIV. Has this been true in your patients? LC: The more mucosal infections someone's had -- whether it's warts, herpes, chlamydia, syphilis -- the more prone that individual will be to have dysplasia [precancerous cells] on that mucosal surface. If I'm caring for an HIV-positive woman who has never had a sexually transmitted disease [STD], her risk for cervical or anal dysplasia is probably no greater than for a comparable HIV-negative woman. But a woman who's had multiple sexual partners, and multiple STDs, should be having regular pelvic exams and colposcopic exams. Analogously, for men or women, anal dysplasia will be seen more in individuals who have a history of chronic rectal infections, with HIV added as a cofactor that reduces immune surveillance and allows the dysplasia to emerge and perhaps develop into cancer. I have some concerns about the emphasis on gynecological care for women with HIV. There are some women who very much need thorough, regular gynecological examinations, and there other women for whom that emphasis could be unnecessary and somewhat misfocused. In other words, some women may get their negative Pap smears and normal gynecological checks every six months and think they're OK overall, when really they may need to be more concerned about the standard problems for which everyone with HIV, men and women, are at risk (vaccinations, PCP prophylaxis, diet education, etc.). HIV can get misconstrued as a gynecological condition in women because in some women, that may be how the disease first shows up. But women who are HIV infected need to have a primary practitioner with HIV expertise, someone other than solely a gynecologist, directing their care. Women in this country are accustomed to getting their primary care from a gynecologist, but gynecologists cannot be expected to be completely familiar with HIV care in women any more than a proctologist would be for HIV-infected men. So we need to stretch the model -- HIV-primary care practitioners (internists, family practitioners) are already familiar with working closely with oncologists, but it may take some getting used to these clinicians working collaboratively with the gynecologist. DS: There was some commotion in the activist community around the phenomenon of false-negative Pap smears. Because of the incidence of misleading smears, shouldn't women with HIV just be given a regular colposcopy [a more aggressive technique than the Pap smear]? LC: I think again you have to consider the individual's history. A reasonable approach is that women should have a baseline colposcopy; in HIV-positive women without risk factors for cervical dysplasia beyond HIV, six-month Pap smears should be sufficient. But if a woman has had multiple STDs, she should have an annual colposcopy, and Pap smears every six months. If at any point either test finds something abnormal, then the screening can be intensified according to what the gynecologist recommends. Fatigue: Hormone Replacement, Other Treatments DS: One of the most common problems for some people with AIDS is unremitting exhaustion. I understand you have used androgenic steroids (male hormones like testosterone) for some of your male patients who are chronically fatigued. LC: Some fatigue, I believe, is attributable to adrenal insufficiencies, either of glucocorticoids (like prednisone) or androgens/anabolic steroids (like testosterone). If someone becomes suddenly tired by just standing up, or walking a few steps, they probably have orthostatic hypotension, or low blood pressure. This can be caused by adrenal insufficiency, which in turn is treatable. (Incidentally, prednisone can be extremely useful for helping people cope with end-stage respiratory distress, such as that caused by pulmonary KS.) But fatigue accompanied by muscle wasting and low libido probably results from androgen insufficiency. Borderline low testosterone levels are often seen in men with ARC or AIDS, and replacing that testosterone can help reverse weight-loss and appetite as well as problems with erections and fatigue. Testosterone cypionate, 200 mg every two to four weeks, has helped some of my debilitated patients, and has not caused any serious side-effects. It has also, I feel, reversed anemia and low platelets in some of my patients. Because of its potential masculinizing effects, I prefer to offer women Megace or Marinol rather than androgens, to treat refractory weight loss and fatigue. In men, Megace or Marinol can supplement testosterone therapy. Of note, the dose of testosterone I use is far below the amounts of anabolic steroids used by body builders. Another possible treatment for either women or men who are emotionally as well as physically fatigued is dextroamphetamine. This can help people through difficult days, make them brighter and more interactive. Survival Trends DS: The statistics on AIDS say that people are living longer. Have you seen that empirically in your practice? LC: Yes, certainly, although in my practice there is a definite bias, because I think my patients tend to have more resources than the average patient with AIDS in this country. I don't just mean money -- I also mean having friends, family or neighbors who will be supportive and will look out for my patients' welfare. As far as statistical survival goes, I see two trends. Many people are living longer, learning how to live with CMV and MAC or other illnesses, but some people are deciding when to stop treatments, which may silently alter the statistics. The issue isn't always how long did someone live after an AIDS diagnosis but how long did they choose to live. Depression and Its Treatment DS: What particular measures would you say might enhance someone's life such that they would choose to live? LC: I have never seen enough emphasis on treating reversible affective disorders, like depression and panic attacks. I have been amazed at how many people with AIDS, people who are dealing with multiple infections and really difficult times, function better day to day with antidepressants. Absolutely. Some clinicians may be hesitant to "cross over" into practicing psychiatric medicine, but we who treat HIV already treat a number of clinical situations that we once would have referred to a specialist. Who doesn't prescribe amphotericin, or erythropoietin, when indicated, rather than referring every symptom to an infectious-disease specialist, or a hematologist? There is an aura around antidepressants that misleadingly implies they are in a completely different realm. I think if primary-care providers only feel comfortable referring psychiatric symptoms to a psychiatrist, they should at least become familiar with recognizing depression and anxiety in their patients. It would be great if those providers also became comfortable treating the patient directly. For logistic and reimbursement reasons alone, it's helpful for patients to not have to go to a number of providers for their care. More importantly, the primary-care physician is often in the best position to pick the right medication. The main concern with antidepressants is not their efficacy, but their side-effect profile. Sometimes you may actually want to exploit side effects, like drowsiness for insomiac patients, or stimulant effects for lethargic patients. You may not always know for sure if the depression or anxiety will respond to medication, but you can't know if you don't try it. If the stigma around using antidepressants comes out of the provider's unfamiliarity with the drugs, then they should familiarize themselves. Perhaps their discomfort stems from talking to their patients about personal, emotional issues; a lot of health-care providers may be dealing with their own depression, since many of them have lost loved ones to this disease. But it's good for the provider to open up so that the patient can open up. And the benefit of doing that is being able to offer the patient a positive healing message: I am looking at you as a whole individual, with dreams and struggles and worries and hopes, and not just a collection of opportunistic infections. In medicine it's actually good to have double vision: to be able to see the ordinary as well as the extraordinary. ***** Clinton Health Care Plan: Major Improvement, But Issues Remain by John S. James President Clinton's proposal for health care reform will clearly be a major improvement over the current system for people with HIV, cancer, and other major illnesses. But there are also potential problems, and areas not yet clarified. In addition, we do not know what will finally emerge from Congress when Clinton is forced to trade off elements of his plan in political compromises. It is important for the AIDS community to be alert to how persons with serious health problems will be affected by the various elements of health care reform which may be proposed and decided over the next months. Some of the major benefits (which could, however, be lost in political negotiations): * Those with no health insurance or Medicaid (about 30 percent of people with AIDS) would get health coverage. However, states will have about two years from passage of the Clinton proposal to implement their health plans and extend coverage to almost everybody. * Medicaid (MediCal in California) now covers about 40 percent of people with AIDS, and coverage varies tremendously from state to state. The Clinton plan will set standards intended to assure a basic level of coverage wherever one lives. Persons on Medicaid who also qualify for SSI or AFDC will have the same benefits and choice of plans as everyone else. It is still unclear how others on Medicaid will be covered. * Those who have private health insurance will not risk losing their coverage -- because they change jobs, because their insurance company controls the rules and finds a way to drop them after learning they are sick, or for other reasons. Persons with "pre-existing conditions" who are now stuck in unsuitable jobs will be able to change. * Prescription drugs will be covered, with patients probably paying $5 or $10 for each prescription. * Health plans "are required to provide coverage for routine patient care associated with approved clinical trials." This should prevent volunteers in trials from being charged for these costs, as often happens today. * While individuals will have to pay some fees for health care, anyone's out-of-pocket costs will be limited to $1500 per year. * People will be able to choose either a managed-care plan, or a fee-for-service plan. Fee for service will be more expensive; but it may be better for persons with special medical needs. In either case, it should be possible to choose a physicians outside the plan and be covered, although one must expect a larger copayment when going outside the plan. The AIDS Action Council, which lobbies the Federal government on behalf of more than 1000 AIDS organizations, strongly supports the Clinton plan. Jeff Levi, policy director at AIDS Action, recently said, "People with HIV will do well under this plan, if its scope is not reduced. We will be fighting against cutbacks and for strengthening key provisions." AIDS Action Council has identified some potential problem areas: * It is not clear that "off label" use of FDA-approved drugs will be covered, even though such use is often the standard of care for persons with AIDS, cancer, and other major illnesses. * Some coverage, such as mental health and substance abuse services, will be phased in slowly, over a number of years. * Massive computerization of patient records will probably occur, and it is not yet clear how confidentiality will be protected. * While the Clinton plan is expected to provide long-term care, emphasizing home and community-based care, there could be problems with eligibility criteria for these services. * Managed-care plans have often been a problem for persons with HIV or other diseases that require expensive and/or specialized care. Patients must have access to HIV experts (not only infectious-disease specialists), without "gatekeeping" by non-experts. They may need to choose physicians outside the plan when necessary. And the plans must have financial incentive to enroll persons with expensive illnesses. The off-label issue is a difficult one with managed-care systems. These are drugs which are approved by the FDA for some medical conditions ("indications"), but are also used for other conditions -- for example, a cancer drug officially approved for certain tumors, but widely used for other tumors as well. They may be standard, accepted, and necessary treatments when used off label, and not officially approved for those uses only because the pharmaceutical company which sells the drug did not do the research and paperwork to gain official approval. The FDA has long made it clear that off- label use can be legitimate and necessary, and that its labeling is not intended to control reimbursement decisions. Managed care plans, however, almost by definition are unwilling to pay for everything a physician might want to do. In the absence of generally recognized standards, the plan may make its own decisions on what treatment is legitimate. But these decision are hardly disinterested ones, since clearly there is a financial incentive to refuse to approve requested treatments. And official standards lag well behind the real standard of care, since it takes time to formalize and certify the actual practices which are accepted by competent physicians. Various ways have been suggested to reduce this problem, including: - Using formularies, such as the U.S. Pharmacopoeia, or lists prepared by medical centers well regarded for HIV (or other specialty) expertise. If a drug usage appeared in any of the accepted formularies, it would be reimbursed. However, there is often a serious lag between actual practice and publication in the formularies. - Holding frequent "consensus conferences" of leading experts, to produce up-to-date recommendations for physicians. Any drug usage recommended by these conferences would be automatically reimbursed. - Treating life-threatening conditions differently than other illnesses. Perhaps any treatment recommended by a physician would be reimbursed, without need for prior approval, unless the treatment had been specifically disallowed for extraordinary reasons. - Having an appeal mechanism, so that an organization with no financial stake could resolve disputes rapidly, without the time and expense required for going to court. Another issue -- raised by the pharmaceutical industry, not by AIDS Action Council -- concerns price controls on new drugs, which may be included in health care reform. Industry supporters argue that the cost of new drugs for life- threatening conditions is only 0.2 percent of the total health care expenditures in the U.S. -- and that without the incentive of sky's-the-limit prices, industry will not bother to develop drugs to save lives. Our own experience in reporting on AIDS treatment development for the last several years suggests that this self-assessment by industry is unfortunately often true; for example, there was little interest anywhere in developing AIDS treatments until AZT broke new ground on prices and made big money. Instead of waiting for an ethical renewal, we might be better off paying the toll, through an exception from any price controls for drugs which advance the treatment of the most significant illnesses; a partial precedent already exists in the favored handling of "orphan drugs" for serious but rare diseases. High prices are less offensive when we all pay through a small percentage, than when the whole burden hits individuals already in a personal and financial crisis. And nothing in medicine is more important than better treatment for life- threatening and disabling conditions, not only for orphan diseases but also for those which affect large numbers of people. ***** Alternative Treatment Library Available The Jon Greenberg Library of Alternative Treatments for HIV Disease, more than 2,000 pages of information on dozens of alternative treatments, is available from AIDS Project Los Angeles (APLA). The collection was compiled by Stephen Korsia, D.V.M., who for three years has been treatment advocate for APLA, where he edited I Heard It Through the Grapevine, "our newsletter about the best and the worst of underground HIV treatments." Korsia worked closely with Jon Greenberg, collecting the information while editing the newsletter. Greenberg urged that the information be made more widely available. Jon Greenberg died on July 12, 1993. Stephen Korsia recently left APLA to accept a job in France, his native country. Before leaving, he organized the information, and arranged for APLA to provide it free to nonprofit organizations, and at cost to others. In a cover letter, Korsia urged caution -- since some of the proposed or promoted treatments listed below are certainly not recommended. "As you will realize as you go through this library, most of the information is pretty raw and requires a certain amount of independent analysis. It is the way Jon and I had intended this to be. No profound analysis, no pontificating judgment, no Truth, just a bunch of information from varied, but often unreliable sources... It is up to you and each person who will read those to make his or her own opinion about the validity of each of these therapies." The collection includes information on: * AL-721; * Aloe vera and acemannan; * Anabolic steroids; * Antineoplastons; * Antioxidants (general information); * Astragalus; * Bitter melon (Momordica charantia); * Cancell; * Carnivora; * Castanospermine; * Cat's claw (Uncaria tomentosa); * Colloidal silver; * Compound Q (trichosanthin, GLQ-223); * Curcumin (turmeric); * DHEA (dehydroepiandrosterone); DNCB (dinitrochlorobenzene); * Echinacea; * Essiac; * FLV-23A; * Garlic; * Herbs (general information); * Homeopathy; * Hypericin; * Immunostimulatory mushrooms (reishi, shiitake, maitake); * Levamisole; * Licorice (glycyrrhizin); * Low-dose oral alpha interferon (Kemron, Immunex); * Malariotherapy; * Melanins; * Mistletoe (iscador); * NAC and glutathione; * NUC-ZM; * Nutrition (general information); * Ozone and oxygen therapies; * PCM-4; * Polio vaccines; * Prunella vulgaris (heal-all); * Pycnogenol; * Qi-gong; * Resist!; * Reticulose; * Ribavirin; * Dr. Roka's treatment; * Shark cartilage; * Siberian ginseng (Eleutherococcus sentiocosus); * Solutein; * Spirulina (blue-green algae); * Swainsonine; * Thioctic acid; * Toxic side effects of herbs; * Traditional oriental medicine; * Transfer factor; * Viroxan (VX-1, VX-2); * Vitamin B12 (cyanocobalamine); * Vitamin C (ascorbic acid); * Vitamins (general information). Copies are free for nonprofit organizations, $30 for others. To obtain a copy, call the Treatment Education Program at AIDS Project Los Angeles, 213/993-1482. Comment: AIDS TREATMENT NEWS is suspicious of a number of the treatments listed, and/or of the promotion behind them. Others on the list might have value, and are certainly worth further study. We publish this list without in any way endorsing treatment ideas, because of the need for information about what has been proposed as "alternative" treatments, both good and bad. We value this compilation because it was put together by people with good judgment, and with no ax to grind for or against any particular approach. ***** Hypericin: Oral Trial Planned On September 15, VIMRx Pharmaceuticals Inc. announced plans to begin a trial of hypericin in an oral dose, probably before the end of 1993. The trial, sponsored by the U.S. National Institutes of Health, is planned for three sites: New York University Medical Center, Beth Israel Hospital in Boston, and a third site not yet selected. The new trial is not recruiting at this time. Background and Update Hypericin is an antiviral compound which is found in the St. John's wort herb, and can also be chemically synthesized. In the laboratory, it is active against many viruses, including HIV and CMV. St. John's wort extracts have long been sold in buyers' clubs and health-food stores, but these products generally contain only a little hypericin, as it is found in the plant in very low concentrations. We do not have independent verification of how much each product contains. An earlier trial at New York University (ACTG 150, also sponsored by the NIH) gave larger amounts of synthetic hypericin intravenously to volunteers. This trial had to be stopped at one of its lower doses, because the drug caused phototoxicity -- abnormal sensitivity of the skin to sunlight or other strong light. Researchers were watching for this side effect, because it had been seen in animals. There is also concern, however, that light might be necessary for hypericin to be effective as an antiviral. We do not know what if any antiviral activity was seen in that trial. At the IXth International Conference on AIDS in Berlin, June 6-11, German researchers reported on successful treatment of 16 of 18 patients for over 40 months, using both intravenous and oral hypericin but no other antiviral treatment. [Steinbeck-Klose A, and Wernet P. Successful long term treatment over 40 months of HIV patients with intravenous hypericin. Abstract # PO-B26-2012.] Note: AIDS TREATMENT NEWS has published a number of reports on hypericin, starting in issue #63 (August 26, 1988). There has been less interest recently, due to the lack of definitive results after five years. We still believe that this potential antiviral is worth testing. ***** Announcements ** Advanced KS: Liposomal Doxorubicin Trial Recruiting, Many Cities Liposomal doxorubicin (brand name DOXIL) is an experimental form of the standard Kaposi's sarcoma (KS) chemotherapy drug doxorubicin. Liposomal drugs are contained in microscopic balls of fat, which can greatly improve delivery to the site where they are needed, allowing more effective doses of the drug to be used, and with less toxicity. Two different studies of DOXIL are now recruiting: * The largest is a randomized trial comparing DOXIL to a standard treatment, ABV [Adriamycin (another name for doxorubicin), bleomycin, and vincristine], for advanced KS. About 100 patients will be randomly assigned to receive each treatment, at about 30 research centers in the U.S. Those who fail on the standard therapy in this trial will be allowed to try DOXIL. This trial includes six cycles of treatment, at two-week intervals, with additional visits for laboratory work on the off weeks, plus additional pre-treatment and followup visits. To find the site nearest you, call the phone number below. * The other, more limited, trial is for patients who have already failed ABV (or BV). They will be given open-label DOXIL, so that they will not be randomized to receive the standard treatment which is known to not work for them. For more information about either of these trials, call the KS HelpLine run by the drug developer, Liposome Technology, Inc., of Menlo Park, California. The number is 800-KAPOSIS, and the hours are 9 to 5 Pacific time, Monday through Friday. Comment Kaposi's sarcoma treatment research has typically moved very slowly, because KS is not a big enough market to interest pharmaceutical companies. DOXIL is an exception. It is being developed very rapidly for KS, because it will likely also be an important improvement for the treatment of certain cancers. KS is not really a cancer. But because the lesions are easy to see and measure, KS provides a fast route to proving that the drug can be useful in medicine, justifying initial approval; then physicians will use the drug for KS, and also use it off-label for cancer. While consumer- protection purists might object, this seems to be a win-win situation, benefiting people with AIDS and people with cancer as well. Much of cancer chemotherapy is off-label anyway; and by the time DOXIL is approved for KS, its human toxicity will be well known -- and probably much less than that of the standard chemotherapy the cancer patients who receive it would otherwise face. ** San Francisco: NAC Trial Recruiting An eight-week trial of NAC (N-acetylcysteine), coordinated by the Herzenberg Laboratory at Stanford University, is now recruiting. The study will be conducted in the Castro district in San Francisco. Its purpose is to learn definitively whether oral NAC can replenish glutathione levels inside T-cells of persons with HIV. (Glutathione levels are often low in HIV infection. It is believed that low glutathione levels may cause the T-cells to work less well, and may also cause faster replication of HIV.) Volunteers will be assigned to take either a large dose of NAC (a total of 9600 mg per day, several times the dose in common use), or placebo, for eight weeks. The study requires eight lab visits to the San Francisco site. Volunteers must be HIV positive, at least 18 years old, and with a T-helper count between 0 and 500. If they are taking AZT, ddI, ddC, d4T, or 3TC, they must have been taking them for at least four months. They must also agree not to start any new nucleoside analogs, antioxidants, antivirals, or immune modulator medications during the eight-week trial. They cannot already be taking NAC, OTC, cysteine, or glutathione. They cannot currently have an acute opportunistic infection requiring treatment, or have chronic diarrhea. There are other medical exclusion conditions, but they should affect relatively few patients. For more information, call Debra Fila, R.N., or Greg Dubs, Ph.D., at 415/863-8090. ** Help Wanted: AIDS Treatment Specialist, Atlanta The Atlanta Chapter of the National Association of People with AIDS is seeking a Treatment Resource Specialist. This program-management position involves treatment activism as well as supervising and maintaining a large treatment resource library. Applicants need the ability to work with a wide variety of people, strong writing skills, the ability to promote seminars and forums, strong knowledge of HIV treatments and treatment issues, and the desire and ability to advocate for treatment reform in Georgia. Salary range $21,000 - 24,000 annually. If interested, send resume and cover letter to: Mark King, Executive Director, Atlanta NAPWA, 44 12th St. NE, Atlanta, GA 30309. No phone calls, please. HIV positive encouraged to apply. ** Spanish Treatment Information: Boletn de Tratamientos Experimentales para el SIDA BETA, the Bulletin of Experimental Treatments for AIDS, is published in English four times a year by the San Francisco AIDS Foundation. Starting in September 1993, a Spanish- language BETA, Boletin de Tratamientos Experimentales para el SIDA, is also being published on the same schedule (March, June, September, and December). Para informacion sobre subscripciones, llame gratis al 1-800- 959-1059. FAX 510-549-4342. Correspondencia editorial: P.O. Box 426182, SaniFrancisco, CA 94142. FAX 415-552-1583. Tel. 415-863-2437 (Lnea de Informacion sobre el SIDA de la San Francisco AIDS Foundation). ** Minneapolis: Skills Building Conference on Influencing HIV/AIDS Policy, Oct. 12 A one-day workshop on the nuts and bolts of lobbying, grassroots organizing, and coalition building, sponsored by the Minnesota AIDS Funding Consortium and the Upper Midwest AIDS Coalition, will take place Tuesday, October 12, from 8 a.m. to 3 p.m. at the Plymouth Congregational Church, 1900 Nicollet Avenue, Minneapolis, Minnesota. It's focus will include Washington and Minnesota issues, how to get involved and influence policy, and strategies which have been successful in Minnesota on similar issues. There is no fee to attend. To register and reserve lunch, call the Minnesota AIDS Project, 612/870-7773. ** California Legislation: Breast Cancer Good News; Others by October 10th Our last issue urged California residents to call Governor Wilson's office to urge him to sign several bills supported by the LIFE AIDS Lobby in Sacramento. As we went to press, we learned that he will sign one of the bills, a 2-cent cigarette tax expected to raise over $30 million for breast cancer research and prevention, at a ceremony on October 1. This bill is widely supported by AIDS organizations; since both research efforts rest on the same basic medical knowledge, progress against one disease will accelerate progress against the other. As we go to press, Wilson has not yet decided on the other bills: * AB 1100 and SB 590, insurance reform to stop "post claims underwriting," dropping people after they start to file claims for an expensive illness. * AB 260, to allow clean needle exchange in local areas that want it. (Our last issue mistakenly said that the bill applied only to San Francisco.) * SB 670, to protect the confidentiality of T-helper tests, now misused by insurance companies. * AB 623, set up licensure requirements for Residential Care Facilities for the Chronically Ill. You can call Governor Wilson's office at 916/445-2864 (Sacramento), or 415/703-2218 (San Francisco). ***** In Memoriam: Jesse Dobson Jesse Dobson, one of the most important AIDS treatment activists ever, died on September 23, 1993, in Oakland, California. He was 35 years old. Jesse, who had a professional background in scientific research, was for years in constant contact with AIDS researchers, working to overcome the lack of national coordination and other obstacles to progress. Most recently he was volunteer director of Project Immune Restoration, an effort of Project Inform to focus research attention on immune-based therapies for managing HIV/AIDS, especially in late stage disease; in this capacity he coordinated two meetings of top AIDS scientists from around the world to develop strategic plans for restoring the immune system of persons with advanced HIV disease, and planned a third meeting, which will occur in November 1993. He had earlier been active on several advisory committees and working groups organized by the U.S. National Institutes of Health, as well as those of other organizations, including the California Office of AIDS, and the American Society for Microbiology. He was also a speaker at many scientific meetings, a founding member of ACT UP/Golden Gate, an AIDS columnist for a San Francisco gay newspaper, and recipient of the AIDS Hero Award from Mobilization Against AIDS in May 1991. Toward the end of his life, Jesse was increasingly optimistic that there will be substantial advances in treating AIDS in the foreseeable future. But he realized that they would not come in time for him. A memorial service will be held on Saturday, October 23; the time and place have not yet been set. For more information, call Ben Collins at Project Inform, 415/558-8669. ***** AIDS TREATMENT NEWS Published twice monthly Subscription and Editorial Office: P.O. Box 411256 San Francisco, CA 94141 800/TREAT-1-2 toll-free U.S. and Canada 415/255-0588 regular office number 415/255-4659 fax Editor and Publisher: John S. James Medical Reporters: Jason Heyman John S. James Nancy Solomon Reader Services and Business: David Keith Thom Fontaine Tadd Tobias Rae Trewartha Statement of Purpose: AIDS TREATMENT NEWS reports on experimental and standard treatments, especially those available now. We interview physicians, scientists, other health professionals, and persons with AIDS or HIV; we also collect information from meetings and conferences, medical journals, and computer databases. Long-term survivors have usually tried many different treatments, and found combinations which work for them. AIDS Treatment News does not recommend particular therapies, but seeks to increase the options available. Subscription Information: Call 800/TREAT-1-2 Businesses, Institutions, Professionals: $230/year. Nonprofit organizations: $115/year. Individuals: $100/year, or $60 for six months. Special discount for persons with financial difficulties: $45/year, or $24 for six months. If you cannot afford a subscription, please write or call. Outside North, Central, or South America, add air mail postage: $20/year, $10 for six months. Back issues available. Fax subscriptions, bulk rates, and multiple subscriptions are available; contact our office for details. Please send U.S. funds: personal check or bank draft, international postal money order, or travelers checks. VISA, Mastercard, and purchase orders also accepted. ISSN # 1052-4207 Copyright 1993 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used.