AIDSNEWS%RUTVM1.BITNET@oac.ucla.edu (AIDS/HIV News) (11/21/89)
AIDS TREATMENT NEWS Issue # 89, October 20, 1989 CONTENTS Mobilizing for Earthquake Relief: The Contrast with AIDS DDI Correction and Update: Phone Number for Physicians San Francisco, San Diego: Oral Ganciclovir Study Dextran Sulfate Not Absorbed, Study Finds San Francisco: AIDS Issues On November Ballot AmFAR Will Fund AIDS Projects in Developing Countries; Deadline November 30 Hemophilia Groups May Boycott or Move U. S. Conference DDC: The Low-Cost Antiviral MOBILIZING FOR EARTHQUAKE RELIEF: THE CONTRAST WITH AIDS Editorial by John S. James The October 17 earthquake killed 10 people in the city of San Francisco; the AIDS epidemic has killed over 200 times as many here. Yet in two days, national institutions mobilized as they have never done in eight years of AIDS. For example: * No one imagines that when an earthquake or hurricane strikes one part of the United States, other parts would turn their backs and say it isn't their problem. Yet with AIDS, impacted cities like San Francisco and New York are left to cope on their own, largely without Federal help. * When a mile-long section of Interstate 880 collapsed in Oakland during the earthquake, killing dozens of people, no one dreamed of delaying rescue efforts until someone could make money off them. Yet when a life-threatening virus has infected hun- dreds of thousands or more in the U. S., and millions in the world, practically nothing moves in AIDS research until corpora- tions smell profits, or academics get grants. Not five years ago, not last year, not today. We do not object to people being paid for their work, or making reasonable profits. We do object to the nearly universal practice of delaying critical research a year, two years, or more, for the sake of financial arrangements -- and to the lack of leadership which allows this practice to continue. For over three years, AIDS TREATMENT NEWS has pointed to obvious, inexpensive, and critical steps needed to save lives. Usually we knew that nothing would be done. Therefore we have had to focus on what people could do for themselves, with or without institutional support. The city official who called the earthquake the worst disas- ter to strike San Francisco since 1906 -- overlooking the epi- demic which has killed 200 times as many -- inadvertently illuminated the crucial but overlooked fact that AIDS has not been treated as a disaster. Outside of the immediately affected communities, there isn't even a pale shadow of the mobilization that the far less deadly earthquake has called forth. How can we address the fundamental lack of national will to save lives? Clarifying and explaining what should be done can help. Protest and political action can help. But ultimately the AIDS community cannot create mobilization which is not there, so we will have to wait for people to become ready. We can only continue to do our work as best we can, for as long as necessary. DDI CORRECTION AND UPDATE: PHONE NUMBER FOR PHYSICIANS The last issue of AIDS TREATMENT NEWS gave an erroneous phone number for physicians to call to register themselves to obtain DDI for their patients. The correct number for physicians only is 800/662-7999. Anyone can obtain information about clinical trials of DDI and other AIDS drugs by calling 800/TRIALS-A. Our last issue correctly stated the three different doses of DDI that will be used in the Treatment IND and the Open Safety (compassionate use) programs, but we did not explain how the doses will depend on body weight. The starting dose of DDI is 375 mg twice a day if patient weight is greater than or equal to 75 kg, 250 mg if 50-74 kg, and 167 mg if 35-49 kg. These doses do not apply to children, as no one under 12 can receive DDI through these programs. For more information, see "DDI Trials, Access Announced," in our last issue. SAN FRANCISCO, SAN DIEGO: ORAL GANCICLOVIR STUDY An oral form of the anti-CMV drug ganciclovir (DHPG) will be tested in patients in a phase I clinical trial. The trial will take place in San Francisco and San Diego, and is now recruiting volunteers. Until now, ganciclovir has only been given intravenously -- a serious drawback since use of the drug must be continued indefinitely. One arm of the study will recruit 12 people with stable CMV retinitis, to see if they remain stable when switched from IV to oral ganciclovir. However, this part of the study may be filled by patients already at the institutions running the trial. The other arm needs 36 volunteers who are HIV positive, are not now taking AZT, and do not have any symptoms of CMV infec- tion. They will be tested for CMV in the urine, which they must have in order to enter the trial. Then they will be given one of three different doses of oral ganciclovir for 28 days, to see if the drug can eliminate or reduce the virus in the urine. (The 12 patients with stable retinitis will only be given the highest dose, to minimize the danger that the retinitis might progress. For those who have no sign of infection except CMV in the urine, however, it is safe to test lower doses.) Volunteers may have used AZT before, but not during the last 28 days; they should not go off AZT in order to enter this study. The reason for excluding AZT is that it usually cannot be com- bined with ganciclovir, because both can cause bone- marrow toxi- city. Volunteers must not now have active PCP, cryptococcal men- ingitis, severe diarrhea, or certain other conditions. They must have over 1000 neutrophils and over 50,000 platelets, and must be between 18 and 60 years old. There may also be other conditions. The study will last 28 days. Volunteers will spend the first two days in the hospital for tests, then come in for daily visits for one week. There will be one whole day of hospitaliza- tion after 2 weeks, and 24 hours at the end of the trial. There is no cost to participate in this study. In San Francisco, patients can volunteer at any of three different medical centers depending on their preference. At San Francisco General, call Chris Kimbrell, 821-5089. At Davies, call Brian Christenson, 565-6153. At Mt. Zion, call Karen Tay- lor, 885-7432. In San Diego, the oral ganciclovir study is not yet open to enroll volunteers. When it is ready, people will probably call the University of California San Diego, Treatment Center, 619/298- 7021. Historical Note Oral ganciclovir has existed for years, but has not been developed, apparently because of the confusion over the official status of the intravenous form of the drug (see "CMV Retinitis -- Ganciclovir, Foscarnet, and Other Treatments: Background, His- tory, and Emerging Controversy," AIDS TREATMENT NEWS #71, December 16, 1988). Intravenous ganciclovir was officially approved for marketing as a treatment for CMV retinitis on June 26. Before then, it had been given free to thousands of patients under compassionate use. A study published over two years ago showed that the drug could be given orally and produce a high enough blood level to inhibit CMV (Jacobson, M. A. and others, "Human Pharmacokinetics and Tolerance of Oral Ganciclovir," Antimicrobial Agents and Chemotherapy, August 1987, pages 1251-1254). However, only about three percent of the drug is absorbed, and it is not clear that oral use will be feasible; that is the question the current study seeks to answer. At least two other oral drugs to treat CMV -- FIAC, and HPMPC- -are being developed. (For background on HPMPC, see AIDS Treatment News #76, March 24, 1989.) Oral ganciclovir could have been developed any time during at least the last two years, and probably much longer. Approval of the intravenous drug, plus the development of potential com- petitors, provided a motive for it to be developed now. As in almost all such cases, no one represented the patients' interest in the matter, as both AIDS organizations and practicing physi- cians chose not to involve themselves in treatment research and development issues. DEXTRAN SULFATE NOT ABSORBED, STUDY FINDS A small trial at Johns Hopkins University found that less than one percent of dextran sulfate taken orally by healthy volunteers was absorbed into the bloodstream -- suggesting that taking the drug orally is unlikely to be useful. This informa- tion, published October 1 in the Annals of Internal Medicine, is not new, but was announced in February by Frank Young, M. D., Commissioner of the Food and Drug Administration. It took until now to be formally published. The research team used three different tests to measure the level of dextran sulfate in the blood. Only one of the methods detected any of the substance after oral use, and the amount was small. By contrast, all three methods showed large amounts of dextran sulfate after intravenous administration. The researchers suggested that future studies administer the drug that way. They themselves are doing so in a small study (see AIDS TREATMENT NEWS #86, August 25, 1989). Incidentally, this study still needs volunteers; persons interested can call Linda Nerhood at 301/955-7703, or Charles Flexner, M. D., at 301/955-9712. After the early an|]wncement by the FDA that oral dextran sulfate was probably not absorbed, sales fell greatly. One buyers' club reported a drop in total sales of 80 percent. Some people have continued to use dextran sulfate, however, and some of them are convinced that it is helping. Comment To us, the history of dextran sulfate shows that the AIDS community can respond appropriately and very rapidly to new information when it is made available in a useful way -- in this case, by an authoritative announcement from the FDA. Persons who were interested in the drug learned immediately that serious doubt had been raised about its value. But some people have chosen to continue using dextran sul- fate, even though they know about the absorption results, because they believe that the drug is helping them. This action seems sensible, too. Much is still unknown; for example, it is con- ceivable that the drug might help some people even if it does not get into the bloodstream, by coming into direct contact with HIV infection in the gastrointestinal tract. Theories are only guides, which may be more or less helpful; ultimately what is important is what works. Unfortunately a very different conclusion was drawn by one of the researchers who did the absorption study. Paul S. Liet- man, M. D., Ph.D., criticized the FDA for allowing patients to obtain unapproved drugs for persons use -- both in an Associated Press story October 2, and in a Johns Hopkins University press release issued a few days later. He called such access "a step backward," saying that "it is wrong to provide drugs of unproven value to patients with devastating diseases." The AIDS community first learned about dextran sulfate over two years ago, when laboratory results suggested that it was one of the best anti-HIV substances yet found. Patients knew that millions of people had used it orally in Japan, where it had been found safe enough to have been sold for 20 years without a prescription. There were doubts about absorption, but it seemed unlikely that millions of Japanese had fooled themselves for 20 years and taken a useless drug. Patients also knew that if the drug did work, it would probably take years to be approved in the United States (in fact it did take two years just for a test for absorption, and for an intravenous trial to start). And with the drug's extensive safety record, the AIDS treatment community knew that the consequences of using it and being wrong would probably be small -- whereas not using it and being wrong could easily have cost tens of thousands of lives. Based on what was known at the time, the decision to obtain dextran sulfate from Japan and use it seems clearly to be the rational one. Conversely, the decision to wait for approval might have been suicidal. We now know that dextran sulfate when taken by mouth is not promising. But decisions must be made on what was known at the time, not what is known two years later. By this standard, we think that the AIDS community has handled dextran sulfate well -- and that calling for police power to prevent people from making rational and compelling decisions about their health care is not helpful. SAN FRANCISCO: AIDS ISSUES ON NOVEMBER BALLOT by John S. James At least two ballot initiatives in San Francisco are relevant to AIDS. It is urgent to get out the vote, because off-year elections are generally weighted toward conservative voters who are least sympathetic toward AIDS. Community-Based Research and Service -- Proposition U This initiative, organized by Mobilization Against AIDS, declares that it is the policy of San Francisco to support com- munity organizations conducting medical research and AIDS ser- vices. There is no legally binding effect. Supporters signing the official ballot argument include the executive directors or comparable officials of Mobilization Against AIDS, San Francisco AIDS Foundation, AIDS Activities at San Francisco General Hospi- tal, Black Coalition on AIDS, American Indian AIDS Institute, Latino Coalition on AIDS/SIDA, and Project Inform. There is no organized opposition. Paul Boneberg of Mobilization Against AIDS said that the reason for the initiative was to put a pro-active measure on the ballot -- to give the public a chance to vote for a positive AIDS measure. If it gains solid support, more substantive initiatives can be developed in the future. While passage is probably assured, the size of the vote will be important. And Proposition U is hampered by lack of public familiarity with community-based research, lack of publicity about the ballot measure, and the fact that many AIDS organiza- tions refused to sign the voter handbook arguments for fear of being "political." Domestic Partners -- Proposition S This measure is not supposed to concern AIDS, but in fact it does. A domestic partners ordinance, passed unanimously by the San Francisco Board of Supervisors and signed by the Mayor, would already be law except for a campaign by conservative religious leaders, who obtained signatures of over ten percent of the voters, requiring the law to be submitted to voters in an elec- tion. The measure would allow unmarried couples to formally register their relationship; they would agree to be jointly responsible for their living expenses, and they would be given the same hospital visitation rights (and bereavement leave, for City employees) as married couples. While supposedly unrelated to AIDS, this measure has in effect become a referendum on the gay community, as a reading of the ballot arguments opposed to it will show. (In one of the official arguments, the word "unnatural" is used three times in two short paragraphs -- and "morally reprehensible" once -- to apply to gay relationships.) Since San Francisco's model AIDS program would not exist without the strength of the gay community here, we are concerned loss of this vote would undermine the City's commitment to AIDS services. Polls show that most San Francisco voters support domestic partners, but a majority of the conservative voters who vote in off-year elections do not. Therefore, getting out the vote is the key to success of this measure. Voters who cannot get to the polls can vote by mail, but the application must be received by the Registrar of Voters no later than October 31. For more information, call the Registrar of Voters, 554-4375, or call the Yes on S campaign, 864-0860. Volunteers are urgently needed, especially starting Friday, November 3. For information call Yes on S, at the number above. Note: Yes on S suspended campaigning for one week to sup- port the Red Cross in earthquake relief. The campaign mobilized over 110 volunteers and raised over $20,000 for the earthquake effort. AMFAR WILL FUND AIDS PROJECTS IN DEVELOPING COUNTRIES; DEADLINE NOVEMBER 30 The American Foundation for AIDS Research (AmFAR) announced a new program to fund AIDS projects carried out in the developing world by non-governmental organizations. Areas of interest include educational projects for professional or lay audiences carried out by local service providers, and small-scale projects to facilitate communications and information exchanges on AIDS. The deadline for letters of interest (not longer than two pages) is November 30, 1989. Letters may be sent by fax to (U. S.) 212/719-0712. For a copy of the September 26 announcement of this program, or for other information, contact Mervyn F. Silverman, M. D., M. P. H., Chairman, International Committee, at the above fax number. Or phone AmFAR at 212/719-0033. HEMOPHILIA GROUPS MAY BOYCOTT OR MOVE U. S. CONFERENCE by John S. James On September 15, the UK Hemophilia Society wrote all member organizations of the World Federation of Hemophilia that it could not participate in the biannual hemophilia conference planned for August 1990 in Washington, DC, because of the exclusion of per- sons who are HIV positive from entry to the United States. Most persons with hemophilia are HIV positive, because they were infected by blood products years in the past before blood was screened for HIV. In May of 1989 the U. S. Immigration and Naturalization Ser- vice (INS) instituted a 30-day waiver to allow HIV-positive per- sons to visit the United States for purposes including attending conferences, obtaining medical treatment, and visiting family members (not for tourism). The UK Hemophilia Society is con- cerned that to obtain this waiver, persons must declare their HIV status and can then be singled out for discrimination. And "peo- ple with hemophilia are immediately identifiable as potential targets" because they are carrying supplies of blood products. The letter urged that the conference be moved out of the U. S. unless the law was changed. It is generally believed that there is no chance that Congress will repeal the provision in the foreseeable future. For HIV-positive persons visiting the United States, the National Gay Rights Advocates in San Francisco has published a 62-page guide on how to obtain the waiver. The INS wants appli- cations 30 to 60 days in advance, but may accept an application after an attempt to enter the United States if the applicant can establish that he or she did not know about the need to apply. There is no routine testing at the border, but the INS can require testing for entry if it has reason to suspect that a per- son is HIV positive -- for example, if AZT or medical records suggesting HIV are found in a search of the luggage. Obtaining the waiver is burdensome. Applicants must show that they are not a danger to public health and can pay for any medical care they may need in the United States, so that there will be no cost to any government here. Extensive documentation is suggested for supporting the application, and anything not in English must be translated and properly certified by the transla- tor. The National Gay Rights Advocates urges anyone to obtain legal advice before submitting an application, because applying can affect all future entry into the United States, whether the waiver is granted or not. For more information, see Visiting the USA: A Legal Guide for Persons with HIV, available for $10. from the National Gay Rights Advocates, 540 Castro St., San Francisco, CA 94110, or call 415/863-3624. History The law excluding persons with HIV was passed in 1987. It was introduced by Senator Jesse Helms (Republican, South Caro- lina) as an amendment to the bill to pay temporarily for AZT for persons with AIDS who had no other way to afford it. The exclu- sion law was passed almost unanimously by Congress, in part as a political trade to obtain the funds for AZT. In April 1989, Dutch AIDS educator Hans Verhoef was jailed for several days in St. Paul, Minnesota when he tried to enter the United States to attend a medical conference in San Fran- cisco. The local INS granted a waiver, but the Washington DC office overruled the local and denied it. An immigration judge then overruled the national office and granted the waiver, and Mr. Verhoef arrived at the conference as it was ending. Before the Verhoef case, the law had not attracted attention in the United States. But in a bizarre incident several months earlier, at least one Canadian had been turned back when trying to enter the United States to obtain medical treatment. This case was front-page, mainstream television news in Canada, but completely blacked out in the United States; as far we can deter- mine, no U. S. news organization reported the story, despite the fact that it very much concerned this country. The Verhoef case led to widespread concern that the interna- tional AIDS conference scheduled for June 1990 in San Francisco would be disrupted by detention of persons trying to attend. Conference organizers pressured Washington for some way to keep that from happening. The result was a May 25, 1989 INS memo intended to codify a waiver policy. This is where the matter has stayed since. Very few people have yet applied for the waiver, so there is little precedent to indicate what documentation the INS will and will not accept as sufficient, or how much the decision will depend on individual officials. Comment Foreigners are justifiably outraged by the U. S. exclusion policy because the U. S. is a net exporter of HIV -- and also is violating World Health Organization principles which the United States itself agreed to. Perhaps the greatest harm from the exclusion of HIV-positive visitors is that it creates an incentive all over the world for people not to step forward for testing within their own countries if they suspect that they might be HIV-positive. Because of the potential economic, personal, and medical importance of being able to enter the United States, and the difficulty and uncer- tainty of the waiver process, many people will find a clear advantage in not knowing their status and ignoring the issue as long as possible. Therefore many people will not know to obtain early treatment if they need it, and not interact with public- health authorities on how to avoid further transmission. The June 1988 report of the Presidential Commission on the Human Immunodeficiency Virus Epidemic -- the famous "Watkins Com- mission" report, probably the most authoritative recommendation on U. S. AIDS ever written -- made nondiscrimination protection a cornerstone of efforts to control the epidemic, so that citizens would come forward and cooperate with public health programs. But now the United States itself is threatening citizens of all other countries with potentially serious consequences for doing just that. Its discriminatory policy creates a hidden disruption in the public health program of every country on Earth whose citizens are free to visit the United States. DDC: THE LOW-COST ANTIVIRAL DDC is an antiviral closely related to DDI, which is widely considered to be one of the most promising new AIDS treatment. DDC may be as effective as DDI, and is currently undergoing large-scale clinical trials sponsored by Hoffmann-La Roche (see two articles in AIDS TREATMENT NEWS #81, June 16, 1989). And DDC costs hundreds of times less than DDI to manufacture, meaning that its potential cost, pennies a day, is within reach of every person in the United States, and of every government in the world. About two years ago, DDC was found to cause serious peri- pheral neuropathy in some patients, and therefore many people gave up on the drug. But now it appears that DDC may be effec- tive in doses much lower than were previously used, and that at these low doses, the toxicity may be rare, and easily manageable when it does occur. We may not have an ultimate answer until the current large-scale trials are completed; these trials are expected to take two years (see "Why No Antivirals: A Case His- tory of Failed Trial Design," in AIDS TREATMENT NEWS #81, cited above). But at least 300 people have so far taken DDC in clini- cal studies -- and others have used "underground" DDC -- and there appears to be enough information available now to make practical decisions. Since most of the world's people with HIV have no access to treatment because of economic obstacles, a drug which eliminates these obstacles deserves careful attention. The true cost of a drug must include not only the cost of manufacture, but also any other costs of appropriate use, includ- ing detection and management of side effects. For example, the cost of using AZT must include the cost of blood tests for hema- tological toxicity, of transfusions when needed, and of the Western medical infrastructure which makes this technology avail- able. But with DDC, the management of toxicity consists largely in not exceeding the proper dose, and stopping the drug immedi- ately if neuropathy does develop (treatment may be resumed later at lower doses). The management of toxicity, therefore, has lit- tle or no economic cost. And this drug does not require the expensive infrastructure of Western medicine; instead, it might be delivered through the traditional healers which are already in place in most cultures. In the United States, the government has claimed exclusive worldwide rights to DDC as an AIDS treatment, and licensed these rights to Hoffmann-La Roche. We checked with a patent attorney, and learned that patent rights are in fact highly geographical, and that it would probably be entirely legal to manufacture DDC for medical use in many countries. In addition, DDC can only be covered by a "use patent" (the weakest of all patents), since the chemical has been commercially available and has been known for over 20 years. A use patent for a drug is violated only at the time of ingestion. In the United States, DDC was available as an "underground" drug over a year ago, but few people used it because of fear of its toxicity. The most serious side effect is peripheral neuro- pathy, often noticed first as pain in the feet. However, the new clinical trial is using a very low dose, .01 milligram per kilo- gram of body weight three times a day. This dose is less than a quarter of what the U. S. "underground" has been using even recently, which itself is much less than the doses which caused serious side effects in the first clinical trials, before it was known how little of the chemical was effective. This .01 dose -- which has enough preliminary evidence for efficacy that a major corporation is willing to test it in hundreds of people -- is so low that for persons of average weight, a single gram of DDC will last for well over a year. In the U. S., both DDC and DDI have sold for about the same price, about $30,000 per kilogram. For DDI, this price translates to hundreds of dollars a month. But DDC is used in such small doses that it will usually cost under 10 cents a day. (Note: the DDC which has been on peoples' shelves for the last year or more may have deteriorated, and must be tested before use.) The official trials of DDC will probably take at least two years to complete. Meanwhile, the AIDS community may want to develop DDC as a treatment for those who have no other option. The whole continent of Africa has been written off, ignored in drug-development decisions because it cannot pay what U. S. com- panies want to charge for their drugs. Within the U. S., minor- ity groups are also likely to be written off -- and many people from all social classes who cannot use AZT will fall through the cracks of the DDI trials and parallel-access system. DDC might be as good a treatment as any that exists today; and it is readily available and there are no economic barriers to its use. But it is also dangerous, and successful ways of using it will not happen automatically; they must be systematically developed. In different countries, for example, the drug would need to be integrated differently into existing health systems. We published this article to point out these possibilities. We call on development experts, AIDS organizations, and others to examine new systems for providing state-of-the-art treatment now, without waiting for bureaucracies to move, for corporations to find profit, or for the time required for national health care to be established, or for a Western medical infrastructure to be created where it does not now exist. STATEMENT OF PURPOSE AIDS TREATMENT NEWS reports on experimental and complementary treatments, especially those available now. It collects informa- tion from medical journals, and from interviews with scientists, physicians, and other health practitioners, and persons with AIDS or ARC. 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. HOW TO SUBSCRIBE TO AIDS TREATMENT NEWS Send $100.00 per year for 26 issues ($150.00 for businesses and organizations), or $30.00 reduced rate for persons with AIDS or ARC who cannot afford the regular rate, to: ATN Publications, P. O. Box 411256, San Francisco, CA 94141. A six-month subscription (13 issues) is $55.00 ($80.00 for businesses or organizations), or $16.00 reduced rate. For subscription information and a sam- ple issue, call 415/255-0588. For the complete set of over 80 back issues, call AIDS TREATMENT NEWS for information. The back issues include articles on DDI, compound Q, fluconazole, AZT, aerosol pentamidine, ganciclovir (DHPG), diclazuril, DHEA, lentinan, peptide T, passive immunoth- erapy, and many other treatments. To protect your privacy, we mail first class without mentioning AIDS on the envelope, and we keep our subscriber list confiden- tial. Outside North America, add $20.00 per year for airmail postage, and $18.00 airmail for back issues. Outside U. S. A., send U. S. funds by International Postal Money Order, or by travelers checks, or by drafts or checks on U. S. banks. Copyright 1989 by John S. James. Permission granted for non- commercial reproduction.