Date: 22 Apr 1999 13:30:59 From: aidsnews@igc.org Subject: AIDS Treatment News #317 AIDS TREATMENT NEWS Issue #317, April 16, 1999 phone 800-TREAT-1-2, or 415-255-0588 CONTENTS: Poppers: Large Cancer Increase and Immune Suppression in Animal Tests New Frontier of AIDS Activism: International Trade Rules and Global Access to Medicines. Interview with Eric Sawyer, HIV/AIDS Human Rights Project Clinton/Gore Top Staffs: Pharmaceutical Background Federal Guidelines for the Treatment of HIV: Free Telephone Conference May 10 Online Chat with Expert Physician, April 28 T-Cell Activation Predictive of Poor Survival in Advanced Disease Fish Oil Reduced Heart Disease in Controlled Trial San Francisco General Outpatient Pharmacy Problems ***** Poppers: Large Cancer Increase and Immune Suppression in Animal Tests by John S. James A new study found that mice injected with cancer cells were more than three times as likely to develop tumors if they inhaled isobutyl nitrite--"poppers"--and that when tumors did develop, they grew four times as rapidly in the inhalant- treated animals.(1) 75% of the mice receiving nitrite developed the tumors in this test, vs. 21% of the control mice (which received the same cancer cells but breathed only air instead). The amount of inhalant used--900 parts per million for 45 minutes a day--was selected to approximate social use of the drug. Other laboratory tests found that isobutyl nitrite did not increase growth of the tumor cells; instead it suppressed certain immune functions, including cytotoxic T lymphocyte (CTL) activity, and the killing of tumor cells by macrophages--which was reduced 86% by 5 days exposure to the inhalation. Previously published work by the same team(2) found that immunity in the mice recovered within 14 days of stopping the inhalant. (The current paper suggested that permanent damage might still be done if immune suppression allowed cancer, KS, or HIV itself, to become established.) This is the first study showing directly that nitrite inhalant can promote tumor growth. Previously, epidemiological studies had found that use of poppers is associated with KS, and also is an independent risk factor for infection with HIV (suggesting that poppers may increase the risk that exposure to HIV will lead to infection). KS is believed to be caused by a different virus, HHV-8, that presents little risk unless the immune system is suppressed by other factors. (The tumor cells used in this research were not KS, but they were a well-known cell line used in animal tests to measure immune suppression.) Comment Malignancies are a major and increasing problem in AIDS, and it will be important to find out if use of poppers is contributing to their higher incidence. One way to research this question would be to ask whether or not patients with lymphoma or other malignancies are more likely than others to have used these drugs. References 1. Soderberg LSF. Increased tumor growth in mice exposed to inhaled isobutyl nitrite. TOXICOLOGY LETTERS, 1999; volume 104, pages 35-41. ***** New Frontier of AIDS Activism: International Trade Rules and Global Access to Medicines Interview with Eric Sawyer, HIV/AIDS Human Rights Project by John S. James Eric Sawyer is a co-founder of ACT UP/New York, and director of the HIV/AIDS and Human Rights Project, a new 501(c)(3) organization. He was one of five U.S. AIDS activists at the March 25-27 meeting in Geneva, Switzerland on compulsory licensing of essential medical technologies--the first time U.S. AIDS activists have attended an international meeting on trade and intellectual-property policies which affect access to lifesaving drugs. About 90% of people with HIV live in developing countries and have no access to modern medicines even when necessary to save their lives--in part because new drugs are usually patented for 20 years and priced for the developed world. When generic copies are available, they often sell for a small fraction of the price; some essential medicines could be sold at a profit for a tenth of their current prices, and be available to millions of people now denied them. The patent holders are multinational pharmaceutical companies, who have little interest anyway in marketing their drugs in poor countries--but the industry is intensely interested in preventing any precedents which might threaten major markets in the U.S., Europe, or elsewhere. Until recently the U.S. government has heard only from industry on this issue, and therefore it has sided completely with the large pharmaceutical companies, and used its economic powers and diplomatic influence to coerce countries around the world to prohibit even the limited relief allowed by international treaties--sacrificing the health and lives of their citizens for the interests of U.S. and multinational companies. As a result, the great majority of the world's people have been written off; if they need a modern drug to save their life, they are out of luck. In the last few weeks there has been explosive growth of efforts to bring this issue to the attention of opinion leaders and the public, so that U.S. and other officials will at least be required to weigh opposing views, and modify the grossly unbalanced policies which today sacrifice essential health needs of millions of people for the most nebulous, symbolic, or ideological wishes of the world's richest companies. Since persons denied medicines do not contribute any money toward corporate profits or research funding--as no sale occurs--it might be possible to develop trade policies and rules which would allow those persons to buy the drugs they need at prices they or their governments could pay, with no loss at all to the patent holders, or even a modest gain through additional royalties. Creativity in designing systems which could work for everyone may be more important than taking away current profits. What is intolerable today is that up to 90% of the people who need modern medicines for HIV, drug-resistant tuberculosis, and other conditions are denied them--partly through poverty, which will be hard to remedy, but also partly through unconscionable trade rules, which sacrifice many of the world's people to maintain high prices for the minority who live in countries rich enough to constitute a viable market. A growing international consensus holds that the current situation is intolerable--that in the future, critical health consequences must be on the table when trade rules and intellectual-property policies would deny access to essential medical care. On March 25-27, in Geneva, Switzerland, about 130 physicians, government officials, industry executives, academic experts, and representatives from dozens of non-governmental health organizations met to discuss these issues. Although this meeting has already been reported accurately (in the FINANCIAL TIMES of London, REUTERS news wire, THE LANCET, and the Web site of the JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION among others), AIDS TREATMENT NEWS interviewed AIDS activist Eric Sawyer for an in-depth look at what is happening now, and how people can help. The interview took place on April 10, 1999. * * * Interview with Eric Sawyer, HIV/AIDS Human Rights Project AIDS TREATMENT NEWS: How was the Geneva meeting important? Eric Sawyer: It was highly educational--an opportunity for everyone involved to learn the perspectives of other stakeholders on this issue, what is happening in various countries, and what the different groups are doing. There were representatives from non governmental AIDS and health groups working on a national level in African countries, Thailand, India, Pakistan and elsewhere; trade representatives from the U.S., South Africa, and Thailand; pharmaceutical industry trade associations, and companies including Glaxo Wellcome, Merck, and Hoescht-Roussel; and generic drug companies from both developed and developing countries [the generic companies have very different interests from the larger and richer companies which sell patented drugs, because they want as much freedom as possible to manufacture and sell low-cost products]. There were also presentations by leading academic scholars in areas including treatment access and patent law. Some of the key concepts are compulsory licensing (a government's ability to issue a license to produce a patented product for an important public purpose, without the permission of the patent holder, under royalty and other terms set by the government), and parallel importing (allowing the importation of a patented drug without the permission of the patent holder--often the identical drug sold more cheaply elsewhere by the same patent holder-- allowing the importing country to get the best price). Compulsory licensing is not the only way a patented drug can be legally produced off-patent. For example, India has not had pharmaceutical patents in the past, but now those laws have to be implemented during a 10-year period under the terms of the TRIPS agreement (Trade Related Aspects of Intellectual Property Rights), part of the GATT international-trade treaty. Some drugs including AZT were manufactured in India before there were any applicable patent laws, and are manufactured there today before India has to comply with GATT/TRIPS. ATN: What was the most important outcome of the meeting? Sawyer: An amazing coalition of like-minded individuals formed there; many people working on patent and trade issues joined in a strong coalition with healthcare and AIDS activists in building a strategic plan to increase access to essential medicines, especially in the developing world. Plans were made for communication mechanisms--fax, mail, and telephone lists, and probably more importantly a number of email list servers--and an overall advocacy strategy to take us through the next couple of years. This strategy includes organizing around certain upcoming events (see "Action Calendar," below). Hopefully the combined efforts of doctors, organizers, generic drug manufacturers who want to protect their ability to produce essential products, and especially government representatives from the developing world, who want to maintain their ability to issue compulsory licenses and do parallel importing, will allow us to protect these provisions of global trade treaties and national laws--one of several necessary components for increased access to medicines in the developing world. ATN: Did pharmaceutical industry representatives say they would try to change the international treaties, to take away the possibility of compulsory licensing and parallel importing of pharmaceuticals? Sawyer: Yes, they did. ** Shut Up or Die ATN: What was most controversial at the meeting? Sawyer: Some industry representatives, after saying that the corporations that hold the patents "paid for" most of the research and development on new drugs for AIDS, tuberculosis, and many other infections diseases, basically threatened that aggressive pursuit of these legal options by health advocates threatened future research and development, especially in areas from which activist pressure was coming. They very pointedly stated that if we in the AIDS community aggressively pursued the protection and defense of compulsory licensing and parallel importing of AIDS drugs, that might directly result in a withdrawal of research and development of treatments for AIDS. Later, I said that as someone living with symptoms of HIV since 1981, I was thankful to the drug industry for still being alive, and that I owed my long-term survival to having access to the latest drugs as soon as they became available. But I was angry with the pharmaceutical industry for not making those drugs available to people in the developing world, because I had to watch my friends who were just as deserving to live die premature deaths, because price gouging by the industry put these drugs out of reach for the majority of people living with AIDS, especially in the developing world--as well as refusal by the drug companies to market their drugs in the developing world. An industry representative said I should indeed by thankful to the drug industry for saving my life, and that I should realize that if it wasn't for its ability to have the levels of profits I was criticizing, research and development could not happen-- and that if I continued with this tactic, very likely research and development on new drugs would dry up--meaning shut up, or we're not going to develop new drugs and we'll let you die. Many in the audience were outraged by his audacity. ** U.S. Policy, South Africa, and Vice President Gore Sawyer: There was also controversy around the presentation of Lois Boland of the U.S. Patent and Trademark Office, who said that the U.S. opposed compulsory licensing and parallel importing, and did not feel these were viable provisions of international trade law. Academic experts, and trade representatives from developing countries, asked if it wasn't hypocritical of the U.S. government to say this is not an option, when the U.S. itself had issued over 100 compulsory licenses in recent years. In several of these cases involving computer technology, the compulsory license provided no royalty at all to the patent holder--a more drastic remedy than what healthcare advocates are seeking for essential medications. Just last week, after the Geneva meeting, we obtained a U.S. State Department document which shows how aggressively the pharmaceutical industry has infiltrated the highest levels of the U.S. government ("U.S. Government Efforts to Negotiate the Repeal, Termination or Withdrawal of Article 15(c) of the South African Medicines and Related Substances Act of 1965," February 5, 1999). This 10-page document, written for three Congressional committees, provides a date-by-date, meeting- by-meeting history of pressure by the U.S. government on the South African government, to get South Africa to repeal a 1997 amendment which allowed for the parallel importing and compulsory licensing of essential medicines in South Africa. It says the State Department understands the desire to make essential medicines available, but then says the U.S. government will defend the profits and patents of its multinational pharmaceutical companies. It's there in detail, including trade sanctions imposed, and ongoing involvement of Vice President Gore, who made pharmaceutical patents in particular a central issue in his discussions with South African Deputy President Mbeki during their meeting in Washington in August, 1998. Ralph Nader and James Love of the Consumer Project on Technology, in an April 8, 1999 letter to Gore, described the document as "chapter and verse of a two year campaign to use the weight of U.S. power, short of military warfare, on South Africa to prevent that country from implementing policies to obtain cheaper sources of essential medicines"--at a time when "public health officials estimate that one in five pregnant women in South Africa are HIV positive, and that more than 45% of the South African military personnel are infected." Some of the top officials on Clinton's staff and on Gore's staff came out of the pharmaceutical industry, either as executives of the companies, or lobbyists in law firms that work for them (see "Clinton/Gore Top Staffs: Pharmaceutical Background," below). And we learned in Geneva that this industry is also putting people into key positions in international organizations as well, where they continue to represent the interests of the industry, not for the larger public interests they were ostensibly hired to serve. ATN: What about the issue of pharmaceutical companies not wanting to market drugs in the developing world anyway? Sawyer: Data from both the pharmaceutical industry and independent academic experts agreed that the developing world accounted for a very small part of the global market in pharmaceuticals, 10% or less. Industry representatives basically said that making drugs available in the developing world through generic mechanisms, or a lower-cost segmented market, would not impact industry profits to any great extent. But they were concerned that if lower-cost equivalent drugs were introduced, that would help erode the huge markets in the developed world, hundreds of billions of dollars per year. Their real concern is that if governments like the U.S., which actually pays for much of the research and development of these drugs anyway, realized how cheaply they can be manufactured and sold, and still at a profit, governments would no longer be willing to pay current prices, and would force price reductions, eroding the profitability of the industry. So this dispute is really about industry continuing the price gouging it does in developed countries. ATN: What is the role of the World Trade Organization (WTO)? Sawyer: The WTO representative gave an honest account of what its authority is, and backed up all the presentations by trade experts and academics about how and why compulsory licensing and parallel importing are legal. But he explained that the WTO was set up to adjudicate disputes, and the secretariat has little real power; ultimately it must rely on the good will of powerful states. [For example, the WTO acknowledges that Article 31 of TRIPS permits compulsory licensing, and it provides information about Article 31 to countries. But bilateral pressure from the U.S. and domestic pressure from industry cause problems for countries. That is why South Africa and Thailand have not yet issued a compulsory license.] ATN: What can people do now? Sawyer: Contact your Congressional Representative and Senators and let them know you are concerned about this issue. Write to President Clinton, and especially to Vice President Gore, and to Health and Human Services Secretary Donna Shalala, and to U.S. Trade Representative Charlene Barshefsky, and let them know you think it is outrageous for the U.S. government to pressure India, Thailand, South Africa, and other governments at the behest of the pharmaceutical industry, to try to prevent them from exercising their right to manufacture or import patented essential medicines for the protection of the public health of their people. Our government should not abuse its power to protect the profits of industry above the human rights of life and health of people in the developing world. Inform yourself about this issue, and about the African trade bills now before Congress, and why activists are supporting the HOPE for Africa Act, and opposing the African Growth and Opportunity Act. Make it clear that the U.S. government must use its position as the world economic superpower to protect human rights and advance access to essential medicines. Because in the global village we have today, the public health of sub-Saharan Africa, India, Thailand, and elsewhere is the public health of the United States. As there is now one global economy, there is also one global public health. We need to start acting accordingly. ** Action Calendar Here are some of the events which will be a focus for organizing around this issue: * April 21 demonstration in Washington D.C., on the Africa trade bills now in Congress (for information, call ACT UP/Philadelphia, 215-731-1844); * The international AIDS Candlelight Vigil, May 16 in hundreds of cities around the world, is organized this year by the Global Health Council (http://www.globalhealthcouncil.org) and Mobilization Against AIDS (http://www.hooked.net/~candle). This year the event will highlight access to treatment; see the Mobilization Against AIDS site for more information, including regional coordinators; * The World Health Assembly, starting mid May, in Geneva; at this meeting the World Health Organization will propose its Revised Drug Strategy, to give WHO a clear mandate to address the public healthy implications of trade agreements, as well as quality assurance and other access issues; * Actions to encourage governments to support the Revised Drugs Strategy; * Ongoing advocacy around the meeting of the international trade ministers, November 26 - December 2, in Seattle, Washington; * World AIDS Day, December 1, which happens to occur during the Seattle meeting of the trade ministers. * And the Health GAP Coalition will continue activism on these issues through the World AIDS Conference in Durban, South Africa, July 9-14, 2000. ** For More Information * Eric Sawyer and the HIV/AIDS and Human Rights Project can be reached at esawyer@igc.org, or by fax at 212-316-0020. * For news and background on the issues discussed in this interview, see the treatment-access forum, www.hivnet.ch:8000/treatment-access; click on 'list of messages'. This electronic discussion includes many issues of treatment access in developing countries; and starting in late March, 1999, there are many reports, documents, and personal messages as well on compulsory licensing and related issues of trade policy and access to essential medical technology. If you have email access only, you can still participate; write to aids98.community@hivnet.ch. * For extensive background and documents, see the Web pages on intellectual property and health care maintained by James Love of the Consumer Project on Technology; start with http://www.cptech.org/ip/health/. This well-designed site includes sections on the recent Geneva meeting, South Africa disputes, compulsory licensing, parallel imports, data exclusivity, and other issues of intellectual property and access to essential medicines. ***** Clinton/Gore Top Staffs: Pharmaceutical Background by James Love, Consumer Project on Technology John Podesta is the Chief of Staff for the President of the United States. He and his brother once ran Podesta and Associates together. Today it is run by his brother Anthony Podesta, and renamed Podesta.com. According to lobbying disclosure reports, Podesta.com represents PhRMA (the U.S trade association that represents the large pharmaceutical companies), as well as individual firms like Genentech, Genzyme (the firm that sells Ceredase, a U.S. National Institutes of Health invention, for as much as half a million dollars for a year of treatment), Serono Laboratories, and other companies. According to 1997 lobbying disclosure reports, Podesta had ten lobbyists working on the Genentech account, six on the Genzyme account, and 11 persons working on the PhRMA account. To illustrate what a small town this is, consider that the VP for government relations at Genentech who hired Podesta was David Beier. Last April David Beier was hired by Vice President Gore to be his chief domestic policy advisor. [Originally published online, titled "Washington, D.C. As a Small Town: podesta.com."] ***** Federal Guidelines for Treatment of HIV: Free Telephone Conference May 10 Leading experts will discuss the Federal guidelines for HIV treatment in a nationwide telephone teleconference on May 10. Participants can ask questions, or just listen. The panel will be John Bartlett, M.D., of Johns Hopkins University, Paul Volberding, M.D., of the University of California San Francisco School of Medicine, Cornelius Baker of the National Association of People with AIDS, and moderator Ron Baker of HIVandHepatitis.com. The teleconference is free, but participants must register in advance. To register--first names only--call 800-880-5121. The teleconference will take place Monday, May 10, at 1 p.m. Pacific time, 4 p.m. Eastern time. For More Information The guidelines themselves are at http://www.hivatis.org. If you miss the teleconference, you can hear a recording later by calling 880-207-2647, 24 hours a day. Also, a transcript will be available at http://www.HIVTreatmentLive.com within about two weeks of the call. If you want to email questions to the panelists in advance, send them to HIVTxLive@aol.com. ***** Online Chat with Expert Physician, April 28 Joel Gallant, M.D., M.P.H., will conduct an online chat for people living with AIDS and their friends and families on Wednesday, April 28, 12:30-2:00 p.m. Pacific time, 3:30-5:00 p.m. Eastern time. To participate, go to http://www.hopkins-aids.edu/chat at that time. Dr. Gallant runs two expert question-and-answer forums on the Johns Hopkins AIDS site, http://www.hopkins-aids.edu, which handles hundreds of questions a month. The chat will allow patients to ask questions that they have not or may not want to discuss with their physicians. ***** T-Cell Activation Predictive of Poor Survival in Advanced Disease A new research paper suggests that abnormal T-cell activation may be more predictive of risk of death than viral load, in patients with advanced HIV disease (CD4 cell count under 50)(1); an earlier report on the same study was presented at the Retroviruses conference over a year ago.(2) This study analyzed stored blood samples collected between 1986 and 1994, deliberately choosing older samples so that the results would not be confounded by the effects of modern, highly active antiretroviral therapies. From 684 HIV-infected men in the Multicenter AIDS Cohort Study (MACS), 37 were selected as meeting the entry criteria for this study. The researchers then looked for differences between the 11 who survived less than six months, and the 26 who survived more than 18 months. They also selected a random sample of HIV-negative men from the same study, to use as a separate comparison group. Immune activation (as measured by expression of CD38 antigen) of both CD4 and CD8 cells was strongly associated with earlier death. Naive cells were low in both those who survived and those who did not. Higher viral load was correlated with CD8 activation, but surprisingly not with CD4 activation--and after adjusting for other factors, viral load was not associated with lower survival. Also, whether or not the viruses used the CXCR4 receptor (meaning that they were SI, or syncytia-inducing viruses) did not predict survival difference in this study. Comment This research is important as progress toward understanding the immune-system pathogenesis of AIDS. But it may not have immediate clinical use, since the CD38 test for immune activation is not readily available. And even if the test were available, it is not clear today how doctors would use it in making treatment decisions. References 1. Giorgi JV, Hultin LE, McKeating JA, and others. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. THE JOURNAL OF INFECTIOUS DISEASES 1999; volume 179, pages 859-870. 2. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998 [abstract 110]. ***** Fish Oil Reduced Heart Disease in Controlled Trial A low dose of fish oil (comparable to eating fish twice weekly) modestly improved the course of coronary atherosclerosis, and appeared to be associated with fewer coronary events, in a major European study. Volunteers were given either a specific fish oil concentrate, or a placebo "with a fatty acid composition resembling that of the average European diet"; the dose was 6 grams per day for three months, followed by 3 grams a day for the rest of the two- year study. 223 patients diagnosed with coronary artery atherosclerosis participated in this study. Hundreds of epidemiological, laboratory, and animal studies had suggested a role for dietary omega-3 fatty acids in reducing atherosclerosis, but there have been few controlled studies, and their results have sometimes been inconsistent. Much is unknown about the mechanism of action of this potential treatment. For example, fish oil has paradoxically been found to increase LDL cholesterol (the "bad cholesterol), especially in patients with elevated triglycerides. Comment This was not an AIDS study; as far as we know all the volunteers were HIV-negative. We noted the article because fish oil might (or might not) be appropriate in treating some patients with lipid abnormalities caused by antiretrovirals or by HIV disease. As information develops, expert panels can prepare nutritional guidelines. References 1. von Schacky C, Angerer P, Kothny W, Theisen K, and Mudra H. The effect of dietary omega-3 fatty acids on coronary atherosclerosis: A randomized, double-blind, placebo- controlled trial. ANNALS OF INTERNAL MEDICINE April 6, 1999; volume 130, pages 554-562. ***** San Francisco General Outpatient Pharmacy Problems By Alex MacDonald Since the closing of a satellite pharmacy at San Francisco General Hospital, long lines and longer waits at the Outpatient Pharmacy of San Francisco General Hospital have alarmed staff, who fear that seriously ill patients will be too ill or become too frustrated to persevere for the hours it takes to pick up a medicine. Since the consolidation of the pharmacies, at least one patient collapsed while waiting and had to be admitted to the emergency room, which is also operating far beyond its design capacity. The crowding and delays in the outpatient lobby result from budget shuffling in response to a projected $30 million shortfall in the Department of Public Health's $802 million budget. Hospital administrators hope to save $1,000,000 by consolidating the hospital's outpatient pharmacies. Waits of four hours are now common, nor is it unusual for patients to leave and try again on another day. When this writer, hoping to avoid a long wait, arrived at the outpatient lobby shortly before the pharmacy opened on Easter Sunday, he found that all the chairs were taken and a small line of elderly and infirm outpatients had already formed. Several complained that this was their second attempt, and one woman said it was her third in as many days. Officials are trying to inform Medi-Cal (Medicaid) patients that they can use any pharmacy they choose. Department of Public Health Director Mitch Katz, in his March 6th report to the Health Commission, said that half of the Medi-Cal patients now use neighborhood pharmacies. In addition, officials hope to persuade people in high places that more money is needed. To that end, they are urging staff to document all patients who have suffered injury or required hospitalization because of the new pharmacy policy. This information, they hope, will convince budget officers that the cuts cost more money than they save. In the meantime, the hospital hopes to raise some money from the patients themselves by requiring a "co-payment" of two dollars for each prescription. The policy, to judge by the Easter Sunday crowd, has frightened many patients, especially those with little income who must take life-saving medications. None seemed aware that the payments can be waived in some instances. Several feared that even at $2 per script, they could no longer manage. On the first day that the new policy was in effect, the pharmacy filled 1,200 prescriptions, according to director Katz, and took in $1,117.75. On an average day, the Pharmacy fills approximately 1,500 prescriptions. Patients can help staff document the human and health effects of the new policies by calling (415) 206-4600. ***** AIDS TREATMENT NEWS Published twice monthly Subscription and Editorial Office: P.O. Box 411256 San Francisco, CA 94141 800/TREAT-1-2 toll-free U.S. and Canada 415/255-0588 regular office number fax: 415/255-4659 email: aidsnews@aidsnews.org useful links: http://www.aidsnews.org Editor and Publisher: John S. James Associate Editor: Tadd T. Tobias Reader Services: Tom Fontaine Operations Manager: Danalan Richard Copeland Statement of Purpose: AIDS TREATMENT NEWS reports on experimental and standard treatments, especially those available now. 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