Subject: AIDS Treatment News #117 Date: Dec 21 1990 (847 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& copyright 1990 by John S. James; permission granted for non-commercial use. AIDS TREATMENT NEWS Issue #117, December 21, 1990 phone 415/255-0588 CONTENTS: [each title is preceded by "*****" ] 1991: Treatments to Watch BI-RG-587: New Antiviral Ready for Trials? AIDS TREATMENT NEWS Selected Index BETA: Clinical Report on Eye Complications Pediatric AIDS: New Date for National Conference ***** 1991: Treatments to Watch by John S. James Two years ago we published a list of treatments we believed would be most important in 1989 (see "Footnote," below). Here is our list for next year. We based our selection primarily on the chance that a treatment could have a practical impact or show major progress in 1991. Despite the pessimism of most of 1990, we find more grounds for hope now than for a long time. First, there might now be changes in the FDA approval process to enable vitally important AIDS drugs to be developed rapidly, which has not been possible before. (AZT was developed rapidly, but in several ways it was a special case which could not be copied by others.) Also, good candidate drugs are coming out of laboratories faster today than ever before. And some potential treatments which have been in process (or in limbo) for years may now be ready to advance toward usefulness in the foreseeable future. There is more depth of interest today than ever before in changing the policies and procedures which made the sacrifice of part of a generation inevitable. But major problems remain. Some of the worst delays in treatment development -- especially in the often-secret preclinical phase, and sometimes in the U. S. Patent Office -- have barely been touched by policy change or advocacy. Research funding is becoming more critical, as money is taken away from research to pay for AZT or other patient care. Congressional advocacy for treatment access has barely begun. To avoid major unnecessary delays and obstacles, community intelligence, communication, coalition, and pressure must continue. Here are the treatments we are following most closely for 1991: (1) ddC and ddI approvals. Although there is no conclusive proof yet, there are strong reasons to believe that either or both of these drugs would be important in medical practice -- that physicians could save many more lives with these drugs in addition to AZT, than with AZT alone. For both drugs, the toxicities and the precautions required are well known. ddI, for example, has already been given to 15,000 people for HIV treatment, through the expanded access program. ddC has not been given to as many people, but it has been in human trials longer than ddI, and it is probably the safer of the two, as it does not cause pancreatitis, the most serious toxicity of ddI. Both drugs are now available to some patients under expanded-access programs. But it is essential that they become available as prescription drugs, for several reasons: (1) The expanded-access programs do not allow combination with AZT -- probably the best way to use ddC, and perhaps ddI also. (2) Many patients who should have access do not meet the criteria for these programs, criteria which could not possibly have been designed to take the full facts of each individual case into account. (3) While the drugs are now "free," the laboratory tests required -- and the physician time required to fill out forms -- are not. These costs, seldom covered by insurance, create greater economic barriers and inequality than paying for the drugs would cause. ddC (although not ddI) is well suited to underground use; in fact a ddC underground has existed sporadically for about two years. But regular prescription access would be far better, offering more reliable quality control, regulatory oversight, private and public insurance coverage, and better opportunities for data collection to improve future therapy. ddC may also be ideal for Third World use, as it costs only pennies a day to manufacture; it has been sold for years, for laboratory use, by chemical-supply companies. Also, management of ddC toxicity requires training of the health-care provider and of the patient, but (unlike with AZT or ddI) it does not require blood tests or other Western medical technology, which is economically inaccessible to much of the world's population. ddC could become the first scientifically tested treatment available to much of the world, forcing a re-examination of the almost universal policy of writing off those already infected and leaving them to die. While U. S. approval would not be legally required for use of the drug elsewhere, it would provide essential credibility and avoid the suspicion that would be aroused by any U. S. -based effort to provide to others a drug not approved for domestic use. Why is there any issue about whether these drugs will be approved? The problem is that despite the weight of information suggesting that the drugs do work, there is no single stack of paper which makes a flawless academic case for efficacy. Each study is either small, and/or unfinished, and/or has no control group for exact comparisons, and/or looked at T-helper counts or other markers, instead of death or major disease progression. And the many patients -- probably many thousands -- who have improved on the expanded-access programs are dismissed because they are not part of a controlled trial. To get perfect data to prove these drugs could take another two years. That is why there is the growing demand that the existing data be analyzed now, and that the drugs be approved if they show "substantial evidence" of efficacy. (See definition of "substantial evidence" from the Senate Report on the Drug Amendments of 1962, quoted in AIDS TREATMENT NEWS issue #112, October 5, 1990, page 2.) (2) New antibiotics for opportunistic infections: azithromycin, clarithromycin, liposomal drugs, and others. Important new treatments for opportunistic infections should be approved in the U. S. or otherwise become more available in 1991. Azithromycin, for example, might be an important advance for toxoplasmosis, MAC (also called MAI), and possibly cryptosporidiosis. Azithromycin has been an approved drug in Yugoslavia for about two years; it is also approved in some other countries in Eastern Europe. In the U. S. the NDA (New Drug Application, or permission to market the product as a prescription drug) was applied for in 1990; with luck azithromycin could be available by prescription in the U. S. in 1991. The labeling will probably recommend it for other purposes than the infections usually associated with AIDS -- simply because those trials were conducted first -- so insurance reimbursement may be difficult. Recently the U. S. sponsor of azithromycin, Pfizer Inc., began a compassionate-use program for persons with toxoplasmic brain infections who have failed conventional therapies or are known to be intolerant to the drugs. Physicians can call Michael DeBruin, M. D., at 203/441-5701, or fax 203/441-5702, for information about enrolling their patients. Unfortunately, azithromycin has not been available in the U. S. through buyers' clubs or otherwise from abroad; at least one physician, however, was able to obtain some for a patient through contacts in Eastern Europe. Clarithromycin, a drug closely related to azithromycin, is approved in Ireland and some other European countries; its U. S. NDA was applied for in 1990, again for conditions not usually related to AIDS. This drug shows considerable promise for MAC (see AIDS TREATMENT NEWS #113 for more information about both clarithromycin and azithromycin). As we reported in issue #113, it is possible to obtain clarithromycin in the U. S. We have heard two reports so far summarizing the resulting early experience with MAC. One was that clarithromycin was highly successful; the other account also reported success, but was cautious because of the small number of patients so far. In New York the PWA Health Group has circulated a survey to physicians asking for results of using clarithromycin for MAC, after four months of treatment. But clarithromycin has only been available there for about two months so far, so none of the forms have yet been returned. Both azithromycin and clarithromycin are used orally. Both are chemically related to erythromycin. Liposomal gentamicin (TLC G-65), another antibiotic, is now in trials for treating MAC. Liposomes are microscopic structures of fats; they are used to improve the delivery of certain drugs to where they are needed in the body, increasing effectiveness and reducing toxicity. TLC G-65 delivers gentamicin inside of macrophages, where MAC organisms would otherwise be protected against the antibiotic. Besides gentamicin, other liposomal drugs now being developed for AIDS-related conditions are amphotericin (a powerful antifungal, now in trials for treating cryptococcal meningitis), and daunorubicin (a chemotherapy agent being developed as a potential treatment for KS). Besides new treatments -- our focus in this article -- more is being learned about how best to use the conventional treatments already available. These studies are also important, since it is too early to know whether the new drugs (for toxoplasmosis, for example) will work better than existing ones. If the new drugs are successful, the ones already in use will probably still be best for some situations. (3) Hypericin. Hypericin is an antiviral found in low concentrations in St. John's wort, a plant which has long been used in herbal medicine. AIDS TREATMENT NEWS covered hypericin extensively from late 1988 through early 1990; see issues #63 (August 26, 1988), #91 (November 17, 1989), and #96 (February 2, 1990) for major reports. We are overdue for an update -- in part because we have waited for clinical trials, which have been about to start since last summer. Only the trials will tell for sure whether hypericin is useful for treating HIV. But what we know today suggests that this antiviral is likely to be valuable and deserves high-priority attention: * In laboratory tests hypericin worked well against HIV. And in animals it worked much better than AZT in preventing death from other retroviruses. (It has been very difficult to infect animals with HIV, so animal retroviruses were used instead of HIV for this test.) For background on antiviral effects of hypericin, see two articles in Proceedings of the National Academy of Sciences, USA: Meruelo D and others, "Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: Aromatic polycyclic diones hypericin and pseudohypericin," July 1988, pages 5230-5234; and Lavie G and others, "Studies of the mechanisms of action of the antiretroviral agents hypericin and pseudohypericin," August 1989, pages 5963-5967. * There is much human experience with oral use of hypericin, especially since St. John's wort extracts with standardized hypericin concentration are sold over the counter in Europe as an antidepressant. The concentration of hypericin in these extracts is very low, probably too low for effective anti-HIV use. But far larger doses of the pure chemical have been given to animals without harm. * A small community-based trial in San Francisco did find a modest rise in T-helper counts in some patients after use of the herbal extracts -- an average 12 percent rise, sustained during the four months of the trial, for those patients who started with high T-helper cell counts. However, this preliminary study did not seek or obtain statistical significance. Another trial with St. John's wort extract is now ongoing at the Community Research Initiative in New York. In short, all the elements are in place to suggest that hypericin should prove to be useful. It works well in laboratory and animal tests. It has been used in humans, although in low doses (but animal studies suggest that, with the pure chemical instead of crude herbal extracts, the doses can be greatly increased). In addition, there are two other reasons why this potential treatment may be important: * The mechanism of action is completely different from that of AZT. If hypericin does work, it will provide physicians with a new class of anti-AIDS drug -- not just another nucleoside analog like ddC or ddI. New possibilities for combination and other therapy will be opened up. * Hypericin also has activity against some other viruses, including CMV and herpes simplex. A recent test found anti-CMV activity at a concentration of one microgram/ml -- about the concentration at which a typical antibiotic is active against bacteria. (Barnard DL and others. Characterization of the anti- human cytomegalovirus activity of three anthraquinone compounds. Interscience Conference on Antimicrobial Agents and Chemotherapy, Atlanta, October 21-24, 1990, abstract #1093.) Unfortunately, it would be difficult to achieve this blood level with the readily available St. John's wort preparations. However, tests reported in a European patent application for use of hypericin as an antiviral (European patent application number 87111467.4, Yeda Research and Development Ltd., Rehovot, Israel, filed August 7, 1987) found much greater activity against herpes simplex; these laboratory tests reported inhibition at 2.5 nanograms (0.0025 micrograms)/ml. Although acyclovir, a safe and effective standard treatment for herpes, is already available, new treatments are needed for acyclovir-resistant strains. The herbal extracts already available at buyers' clubs should be tested for this purpose. Underground research with higher doses of hypericin (as a potential HIV or CMV treatment) would be possible, since chemical extraction of hypericin from the St. John's wort plant is relatively easy. We hope that the ACTG (AIDS Clinical Trials Group, of the U. S. National Institute of Allergy and Infectious Diseases) trial planned to start soon at New York University will make underground research unnecessary. The AIDS Clinical Drug Development Committee of the ACTG put hypericin in its highest priority category in May 1990. It is hoped that the first trial with pure hypericin (not the very-low- dose herbal extracts) can start early next year. What is needed now is a first look at efficacy of hypericin, to test whether or not this drug may be a "home run" in the treatment of HIV. If so, far more resources would be made available than are now being applied to its development. If not, then we could afford to wait for the larger, and probably slower, trials which would be needed to determine whether it could make a more modest contribution. (4) Compound Q. We have not followed compound Q (trichosanthin) closely, as we have left this treatment to Project Inform, which is directly involved in the research. Reports we have received, not only from Project Inform but also from individuals who have used the drug, are usually good. It is well known that there are serious risks in using this treatment; expert supervision is essential, because occasionally there are severe side effects which could be fatal if not treated immediately. At this time, the physicians and researchers testing compound Q are still learning how to use it best. Large-scale "pivotal" trials -- those designed to lead to drug approval -- may need to wait until more of this preliminary research is finished. (5) Protease inhibitors. This class of drugs has attracted intense interest among major pharmaceutical companies. Much of the work is secret, however; therefore it has been difficult to cover this area well. Protease is an enzyme which is necessary for HIV to reproduce. When a new copy of the virus is being created by an infected cell, a single long string of amino acids (the components of protein) is produced. This single string must be cut in the right places to form the pieces which need to be assembled in a new virus. The protease, which is on one end of the original string, does this cutting. If the protease does not work, defective copies of the virus are formed, and they cannot reproduce. HIV protease is only created by infected cells; it has no normal function in the body. Protease inhibitors are drugs to temporarily or permanently disable this enzyme, without harming normal cells. Different protease inhibitors are being developed by different companies. At least one is expected to enter Federally funded human trials (within the ACTG system) within the next few weeks. (6) Tat gene inhibitors. "Tat" is a gene of HIV which regulates viral activity. Human trial of drugs to inhibit the tat gene may begin in early 1991. (7) Non-nucleoside-analog RT inhibitors. Reverse transcriptase (RT) is an enzyme necessary for reproduction of HIV; it is not used by human cells. Therefore, RT is a natural target for anti-HIV drugs. AZT, ddC, and ddI are RT inhibitors. But they are also nucleoside analogs -- meaning false building blocks of DNA. Because they can sometimes interfere with human DNA, drugs in this class tend to be toxic and cause side effects. But other drugs, which are not nucleoside analogs, can also inhibit RT. Some of these may have effective anti-HIV activity without the toxicity of nucleoside analogs. A number of companies are developing such drugs (see "Drug Concerns Make Big Strides in AIDS Work," The Wall Street Journal, December 7, 1990); until recently, however, this work received little public attention. One group of non-nucleoside RT inhibitors which has been well known is the TIBO derivatives (see AIDS TREATMENT NEWS issue #97, February 16, 1990. An early human test in Europe of one of these drugs may have been disappointing; according to AmFAR's AIDS/HIV Treatment Directory, "no significant immunologic or virologic improvement was noted" in the 10-patient dose escalating trial. Other TIBO derivatives may be tested. Another kind of non-nucleoside RT inhibitor is BI-RG-587, described below in this issue. (8) Kaposi's sarcoma: anti-angiogenesis treatments. The much-rumored new KS treatment in Japan, mentioned by Dr. Robert Gallo of the U. S. National Cancer Institute (see AIDS TREATMENT NEWS issue #99, March 16, 1990) is believed to be a drug which prevents abnormal angiogenesis (growth of blood vessels). Apparently this drug is difficult to produce, and U. S. researchers have not been able to obtain enough for human tests. Therefore they are looking for substitutes; one possible substitute, pentosan polysulfate, is now being tested at the National Institutes of Health. We have heard mixed reports about pentosan. Angiogenesis treatments are also likely to be important for cancer, as solid tumors must cause blood-vessel growth in order to obtain nourishment and grow beyond a small size. (In KS, the abnormal blood-vessel growth itself is the main problem.) Since new blood vessels do not normally grow in adults, except in wound healing, drugs to stop this growth may be feasible for treatment use. A important report on a new anti-angiogenesis compound appeared in Nature, December 6, 1990 (Ingber and others, "Synthetic analogues of fumagillin that suppress angiogenesis and suppress tumour growth," pages 555-557). In mice the compound inhibited solid-tumor growth with few side effects. This report does not mention KS or AIDS, however, so it may not receive the attention in the AIDS community which it deserves. Footnote: January 1989 Predictions Almost two years ago (issue #72, January 13, 1989) we listed the following as likely to be important in 1989: ddI; passive immunotherapy; hypericin; compound Q; Chinese anti-infection herbs; FLT (fluorodeoxythymidine); AzdU; d4T; and soluble CD4. Looking back after two years, it is striking how little has been accomplished for most of them, in view of the seriousness of the AIDS emergency. Most remain today as they were then: still promising, still untested. Several remain on our current list for next year. A note about our two least successful predictions: We added soluble CD4 to the end of the list against our own judgment; it had so much mainstream support that we feared we had overlooked something. What we had overlooked was a 70 million dollar investment, including millions of dollars in first-class basic research opportunities for scientists, which may have kept this drug alive long past its time. (New variations of CD4 are now being developed; some of them might prove useful in the future.) Why were we unenthusiastic? What standards do we use to judge which drugs should go on the list? First, we look for evidence of efficacy; does the drug work in humans? Is there any evidence that it does not work? Unfortunately, for most potential treatments, no good studies have been done, so there is no clear evidence concerning efficacy. In the absence of efficacy information, we look for a well- supported scientific rationale, together with evidence of safety, or extensive human experience so that toxicities are well known. After that, we look at availability (including ease of manufacturing, and probable price range), ease of use, and ease of testing (to see if the drug works). Soluble CD4 did have a good rationale, and was quickly found to be safe. But it was difficult and expensive to manufacture, and difficult to administer, so we did not pursue it. (Any reliable information that a drug works, of course, could quickly outweigh such drawbacks.) FLT (another drug that we listed in January 1989) had been found more effective than AZT against HIV in the laboratory, and against the related SIV (simian immunodeficiency virus) in monkeys; these results had been announced by leading virologist Professor Bo Oberg of the Karolinska Institute in Sweden. The drug had been tested in humans 20 years ago as a cancer therapy, but abandoned. A Swedish company was trying to sell rights to a large pharmaceutical company. A recent computer search found no published articles in the last ten years about this drug. We do not know if it just fell through the cracks, or if it was rejected for a reason. But because there is human experience with FLT, the drug would be easier to test as an HIV treatment than one never used in people before. For example, an early trial might test whether it raises T-helper counts within eight to 12 weeks. Note: Last year we did not publish a list of treatments for 1990. Instead, we listed three developments as likely to be important in that year: viral tests for rapid drug trials; affordable treatments for the Third World; and the Sixth International Conference on AIDS in San Francisco. We would have been more accurate if we had described this list as a wish as well as a prediction. ***** BI-RG-587: New Antiviral Ready for Trials? by John S. James A December 7 report in Science1 on laboratory and animal tests of a new AIDS antiviral has generated more than usual interest. Many AIDS laboratory findings appear in technical journals and are then picked up by the press, but most are not heard from again. The reason for the greater interest in this drug seems to be that the major practical bases have been covered well. With luck, U. S. human trials could begin by early or mid 1991. The antiviral, named BI-RG-587, was found by a systematic strategy for synthesizing and screening chemicals likely to be active against HIV-1 reverse transcriptase (RT), but without the toxicity of the nucleoside analog RT inhibitors such as AZT, ddC, and ddI. BI-RG-587 inhibited several strains of HIV-1 at low concentrations (under 50 nM) in cell cultures. Over 8,000 times the concentration was needed to be toxic to human cells. The chemical was so specific to HIV-1 that it had no effect on HIV-2, or on any other virus tested; this great specificity may help to reduce side effects. BI-RG-587 was also effective against HIV-1 strains obtained from four patients using AZT; we do not know the concentration used in these tests. In animals, BI-RG-587 could be given orally. In monkeys, a single dose produced plasma levels 35 to 140 times the concentration needed to inhibit HIV-1 in the cell-culture tests, and these levels were maintained during an eight-hour period. In chimpanzees, 600 times the required concentration was achieved. The drug did cross the blood-brain barrier very well in the animal tests. BI-RG-587 is a simple molecule which appears not difficult to synthesize -- important so that if it proves effective, there will not be delays due to manufacturing problems. The developer of BI-RG-587 -- Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut -- was not previously known to be working on AIDS. However, rumors were furiously circulating shortly before the December 7 announcement, suggesting that the German parent company was starting tests of an AIDS drug. AIDS TREATMENT NEWS has learned that the U. S. company has plans to file an IND (Investigational New Drug application) in January 1991, and has hopes of starting a U. S. trial by March. Despite encouraging laboratory results, only human trials can tell if the drug will work. Another non-nucleoside RT inhibitor -- a TIBO derivative, the first one tested in humans -- showed similar promise in laboratory and animal tests, but seems not to be effective in patients. Other companies also are developing their own lines of non-nucleoside RT inhibitors. No one knows in advance which ones will be successful. But what can be done is to make sure that there are no unnecessary obstacles or delays in finding out. References 1. Merluzzi VJ, Hargrave KD, Labadia M, and others. Inhibition of HIV-1 Replication by a Nonnucleoside Reverse Transcriptase Inhibitor. Science. December 7, 1990; volume 250, pages 1411- 1413. ***** BETA: Clinical Report on Eye Complications The November 1990 issue of the Bulletin of Experimental Treatments for AIDS (BETA) offers a thorough overview of HIV complications in the eye, by Robert Neger, M. D. The article describes symptoms and treatments for eye involvement with CMV, herpes simplex, herpes zoster, molluscum contagiosum, Pneumocystis and Toxoplasma infections, as well as optic neuritis and KS lesions. Dr. Neger practices ophthalmology in San Francisco, and shares a number of points and precautions accumulated from his clinical experience. The same issue of BETA also includes an interview with one of the developers of ddI, Dr. Robert Yarchoan of the National Cancer Institute. For information about subscribing to BETA, interested persons can call the San Francisco AIDS Foundation, 863-AIDS from within San Francisco and 800/327-9893 from elsewhere in the U. S. (From other countries, call 415/863- 2437.) ***** Pediatric AIDS: New Date for National Conference The Sixth Annual National Pediatric AIDS Conference, first slated for last October but then canceled, has been rescheduled for February 9-12, 1991. As planned before, the Conference will be held in Washington, D. C., and is sponsored by the respective maternal and child health agencies of The U. S. Department of Health and Human Services and the District of Columbia Commission of Public Health. Registration fees and airline tickets purchased for the October dates can be applied to the February event, or will be refunded on request. A keynote speaker will be U. S. Surgeon General Antonia C. Novello, M. D., M. P. H. Dr. Novello is a pediatrician, and brought to her position personal experience with treating HIV- infected children. The Conference's advance programming appears to focus primarily on epidemiology, social programs, and the developing network of family and community care-givers. For information about registration forms for the Conference, which should be mailed by January 8 to qualify for a reduced registration fee, interested persons should call Amy Mattingly or Elena Widder at 301/718-0581. Their fax number is 301/986-4553. ***** AIDS TREATMENT NEWS Selected Index compiled by Denny Smith Readers of AIDS TREATMENT NEWS often write to ask us if we ever reported on a particular treatment or diagnosis. The first 75 issues of the newsletter are thoroughly indexed in our book, AIDS TREATMENT NEWS, published by Celestial Arts, of Berkeley, California. But no such index has been available for issues #76 through the present. The following selective index is maintained and used in our office to answer inquiries. It does not include every possible reference from our back issues, only those which still seem substantial or relevant. For information concerning topics not addressed by AIDS TREATMENT NEWS, we recommend the following other publications to our readers: *AmFAR's AIDS/HIV Experimental Treatment Directory: 212/719-0033. *Bulletin of Experimental Treatments for AIDS (BETA): 863-2437 in San Francisco, 800/327-9893 rest of U. S. *Directory of Antiviral and Immunomodulatory Therapies for AIDS (DAITA): 205/991-6920. *PI Perspectives and Project Inform fact sheets: 558-9051 in San Francisco, 800/334-7422 rest of California, 800/822-7422 rest of U. S. ; 415/558-9051 from other countries. *Treatment and Data Digest of ACT UP/New York: 155 E. 31st Street, Suite #20-L, New York, NY 10016. *Treatment Issues, published by Gay Men's Health Crisis: 212/337-1950. Article Issue Numbers ACT UP 82, 101, 103, 106, 108, 111, 112,117 acyclovir (Zovirax) 83, 94, 108, 115 aerosol pentamidine 88, 90, 114 AL 721 (egg lecithin/lipids) 42, 43, 44, 55 alpha interferon 75, 87, 101 amikacin 109 amphotericin 41, 58 Ampligen 34, 67 Antabuse (disulfiram) 29, 70 anemia 82 anti-idiotype antibody therapy 93, 110 Asacol 109 ascorbate 111 aspirin 109 AzdU (azidouridine, CS-87) 72 azithromycin 75, 79, 108, 109, 111, 113 AZT (zidovudine, Retrovir) 83, 86, 90, 95, 100, 107, 110, 113, 115 Bactrim (co-trimoxazole, TMP-SMX) 108, 114 benefits 74, 76, 105 BHT 10, 71 BI-RG-587 117 bleomycin 73 blue-green algae (sulfolipids) 87, 99 buyers' clubs 117 candidiasis (thrush) 37, 96 castanospermine 35 CDA (chlorodeoxyadenosine) 93, 110 CD4 (recombinant soluble) 62 chemotherapy 73, 75, 93, 110 children/infants 90, 114, 117 Chinese medicine 61, 68, 75, 93, 107 Chronic Fatigue Syndrome (CFIDS) 93 cimetidine (Tagamet) 80 clarithromycin 109, 113 clindamycin 79, 104, 108, 111 clofazimine (Lamprene) 79, 109 CMV 71, 76, 83, 89, 94, 96, 108, 110 coccidioidomycosis (valley fever) 41, 96 cofactors 83, 108 coenzyme Q (ubiquinone) 26 combination therapies 107, 115 community research 65, 66, 83, 85 compound Q (GLQ 223, trichosanthin) 82, 88, 99, 104 computerized information 83, 102, 114, 116 CPFs 108 cryptococcal meningitis 41, 58, 96, 99 cryptosporidiosis 49, 58, 75, 80, 95, 107, 111, 113 cytarabine (ARA-C) 79, 93 d4T 72 dapsone 79, 114 ddC 89, 103, 104, 112, 113, 115 ddI 83, 88, 99, 103, 110, 112 dementia 97, 101 dextran sulfate 50, 76, 89 dexamethasone (Decadron) 79, 88, 93 DHEA (EL 10) 48, 49, 84 diagnosis accuracy 100, 111 diclazuril (Clinicox) 80, 95, 107, 111 DNCB 14, 116 doctor/patient relations 100, 111 doxorubicin (Adriamycin) 73 doxycycline 95, 104, 108 D-penicillamine 35 DTC (Imuthiol) 29, 70, 114 eflornithine (DFMO) 94, 95 encephalitis 79, 97 epidemiology 97, 99 EPO (erythropoietin) 82 Epstein-Barr Virus (EBV) 93, 94 etoposide 73 Fansidar 42, 108, 114 FIAC 94 566C80 108, 109, 114 FLT (fluorodeoxythymidine) 72 fluconazole (Diflucan) 41, 58, 80, 96, 103 Foscarnet 71, 83, 94, 108, 110 funding/lobbying 97, 99, 111 fusidic acid (Fusidin) 42, 79 gamma interferon 108 ganciclovir (DHPG, Cytovene) 71, 89, 94, 96, 108 gentamicin 109 germanium 90 glycyrrhizin 17, 103, 115 GM-CSF 87, 93, 94, 105, 108, 110 health care politics 99, 102, 103, 111, 112 hemophilia 89, 102, 103 heparin 100 herpes/shingles 80, 83, 94, 100, 115 histoplasmosis 41, 96 HOE/BAY 964 59 HPMPC 76, 96 Humatin (paromomycin) 107, 111 hybridons (anti-sense) 58 hydrogen peroxide 49 hypericin 80, 86, 88, 91, 96 hyperimmune milk (colostrum) 49, 95, 107 hyperthermia 104 ibuprofen (Advil) 109 immigration 89, 98, 114 Imuthiol (DTC) 29, 70, 114 indomethacin 109 infection prevention 79, 90 insurance 74, 76 interferons 75, 87, 101, 114 Iscador (mistletoe compound) 92 isoprinosine 106 ITP 48 itraconazole (Sporanox) 80, 96 Kaposi's sarcoma (KS) 73, 75, 87, 99, 100 Kemron 97, 101, 114 laser treatments 75, 96 lentinan 19, 73 leucovorin 49, 52, 79 liposomes 109 L671,329 114 lymphoma 93, 110 MAI/MAC 79, 109, 113 mebeciclol 95 Megace (megestrol acetate) 76, 77 MEK 99 melanins 107 mitoxantrone 93 mycoplasma 95, 108 NAC 88, 92, 93 naltrexone 16, 52 neopterin 86, 100 neutropenia 94, 100 neuropsychiatric effects 97, 101 nonsteroidal anti-inflammatory drugs 109 nutrition 73 ozone 80 parallel track 82, 84, 85, 104 paromomycin (Humatin) 107, 111 passive immunotherapy 67, 92 patient/doctor relations 100, 111 PCR 62 pediatric AIDS 90, 117 people of color 86, 99 Peptide T 84 Persantine (dipyridamole) 79 pharmacies 64, 86 physician interviews 47, 54, 56, 62, 100, 106 PML 79, 88, 100, 115 Pneumocystis pneumonia (PCP) 58, 83, 90, 106, 114, 115 polio vaccine 45 pregnancy 90 primaquine 113 prisoners 106 prophylaxis/prevention 79, 94, 100, 106, 108, 114 propolis 37 Prosorba column 75 PWA coalitions 117 pyrimethamine (Daraprim) 79, 104, 108, 114 radiation therapy 73, 93, 110 research priorities & policy 60, 62, 67, 77, 78, 81, 85, 104, 105, 110, 112, 116 R-HEV test 85 rifabutin (Ansamycin) 53, 79, 109 rifampin 79, 102 roxithromycin 75, 81, 95 Salk vaccine (HIV) 98 scabies 98 SCH 39304 99 Septra (co-trimoxazole, TMP-SMX) 79, 108, 114 shiitake 19 somatostatin (Sandostatin) 58, 95 spiramycin 49, 79, 95, 107 steroids 114, 115 sulfadiazine 79, 93, 104, 108 sulfolipids (blue-green algae) 87, 99 sunlight 58 Tagamet (cimetidine) 80 thrush (candidiasis) 37, 96 TIBO derivatives 97 TI-23 108 TLC G-65 109 toltrazuril (Baycox) 111 toxoplasmosis 79, 104, 108, 109, 113 transfer factor 47 treatment access 83, 84, 85, 115, 116 treatment strategy 83, 100, 111 trifluridine (Viroptic) 115 trimethoprim/sulfamethoxazole 79, 108, 114 trimetrexate/leucovorin 49, 52, 108 tuberculosis 106 tumor necrosis factor 87, 88 valley fever (coccidioidomycosis) 41, 96 vidarabine (Vira-A) 79, 94 vinblastine, vincristine 73 vitamin C 111 wasting syndrome 76, 77, 88 women 65, 90, 111, 112, 115 ***** Statement of Purpose AIDS TREATMENT NEWS reports on experimental and complementary treatments, especially those available now. It collects information from medical journals, and from interviews with scientists, physicians, and other health practitioners, and persons with AIDS or HIV. 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. We also examine the ethical and public-policy issues around AIDS treatment research and treatment access. [Obsolete subscription information has been removed. See the latest issues for up-to-date information. -- sysop] &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display