Subject: AIDS Treatment News #339 Date: Mar 17 2000 (712 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& Copyright 2000 by John S. James; permission granted for non-commercial use. AIDS TREATMENT NEWS #339, March 17, 2000 phone 800-TREAT-1-2, or 415-255-0588 CONTENTS: [items are separated by "*****" for this display] ** Treatment Models from India: Interview with Shashank Joshi, M. D. An HIV specialist in India describes an evolving standard of care, when only a few patients can afford the antiviral regimens common in richer countries. Dr. Joshi's approach include nutritional support for the immune system, intermittent HAART for some, herbal treatment, de-worming, and sometimes drugs to reduce intestinal inflammation and therefore possibly lower viral load. ** Testosterone Cream Available at CPS; Gel Approved by FDA A major HIV-specialist pharmacy is now carrying a compounded testosterone cream for topical application, avoiding the shots or patches otherwise used to deliver this drug. Meanwhile, the FDA has approved a testosterone gel -- but this gel will not be widely available for several months. ** Anabolics, Exercise, Nutrition, Supplements: New Book Available BUILD TO SURVIVE, by the editors of the newsletter MEDIBOLICS, discusses anabolic steroids, exercise, nutrition, and supplements for preventing or treating muscle wasting in AIDS. ** Vaccine News, March 2, 2000 Much is happening to accelerate development of vaccines, especially for AIDS, tuberculosis, and malaria. Major initiatives were announced at a meeting of the President's Millennium Vaccine Initiative, March 2 at the White House. ** Fluconazole: Pfizer Asked to Lower Africa Price Pfizer, Inc. 's fluconazole costs almost 15 times as much in South Africa, where it is patent protected, than in Thailand where it is generic. The result is that many Africans die of cryptococcal meningitis and other fungal infections because they cannot obtain the patented drug at Pfizer's price. In South Africa, a coalition of major organizations has asked Pfizer to either reduce the price to the Thailand level, or voluntarily license the patent so that the treatment could be made available. ** Dietary Supplement Regulation: FDA Public Hearing April 4, Written Comments Due May 4 Problems in how the U.S. regulates "foods" vs. "drugs" could eventually block access to low-cost and natural treatments. ** FDA Drug-Approval Background: New Web Pages An FDA Web site explains the details of how drugs are regulated. ** African Americans and AIDS: Highlights of 2nd Annual Washington Conference Treatment and prevention experts look at how to respond to the epidemic among African Americans, who are much more likely than whites to have HIV and AIDS. ***** Treatment Models from India: Interview with Shashank Joshi, M. D. by John S. James Shashank R. Joshi, M. D., president of the HOPE Foundation in Mumbai, India, is an HIV specialist in a public hospital system with more than 36,000 patients with HIV; in addition, he follows over 500 HIV patients in his private practice, and more than 180 HIV-discordant couples. We asked Dr. Joshi to share information and experiences that might be useful to physicians or patients elsewhere. An Evolving Standard of Care in India AIDS TREATMENT NEWS: How to you approach HIV care in India, where few patients have access to triple-drug combination antiretroviral treatment? Dr. Joshi: We are developing low-cost treatment models in the Indian population, because of the high cost of antiretroviral drugs. A few of my private patients can afford some triple therapy with a protease inhibitor and two nucleoside analogs, but not continuously. So for some patients, we suggested triple therapy on alternate months, one month on a HAART combination and the next month without antiretrovirals. At the end of a year we have a small cohort of 26 patients who have done very well on this treatment; all of them have undetectable viral load -- below 20 copies on the Roche Ultrasensitive test -- and their average CD4 count has improved. It is important to note that all of these patients started this regimen with a CD4 count over 300. NIH is critically looking at this cohort. We are now trying to validate these results, and are working with other researchers, including in the U.S. We are looking at other low-cost models as well. We do not have ddI in India, so often I use d4T, 3TC, and hydroxyurea, in an antiretroviral-naive population. [Note: Hydroxyurea, an inexpensive drug usually used in cancer treatment, may improve the activity of certain antiretrovirals, especially ddI -- but can also increase the toxicity of the regimen.] This combination is working very well in a small but significant number of cases, reducing viral load and inducing CTL responses. Significantly, we have had no mitochondrial toxicity in these patients -- perhaps because we are giving them appropriate immunonutrition, including multivitamins, antioxidants, and certain other micronutrients. This nutritional therapy may be particularly important in the Indian population, because wasting is a major problem. [Note: Some researchers believe that mitochondrial toxicity -- a condition recognized elsewhere in medicine -- may caused by nucleoside analog drugs -- and may be responsible for much of their toxicity, as well as some but not all of the body-shape changes often attributed to protease inhibitors.] We are planning to study the product ImmunoCal, a nutritional supplement derived from whey protein, as a source of glutathione. It is believed that mitochondrial toxicity, which the nucleoside analog drugs and hydroxyurea may have, is mediated through the glutathione pathway. If you give patients a natural source of glutathione, maybe this problem can be prevented, and you may not see the liver toxicity, lactic acidosis, or other problems which might otherwise occur. We want to see if improved nutrition can improve the catabolic cachexia [wasting], and also we want to look for any antiretroviral effect. I understand that a small but significant number of patients have dropped their viral load by a log, after treatment with nutritional regimens designed to support the immune system. So an evolving standard of care in India is that we offer patients antiretroviral therapy with two nucleoside analogs and a protease inhibitor; if they cannot afford that, they can try structured treatment interruption, one month on and one month off of the triple therapy; if they cannot afford that, we look into an option like d4T and 3TC and hydroxyurea. In any case, treatment includes multivitamins and antioxidant supplements, psychological support, and meditation and yoga. Our protocol always includes vitamin E and vitamin C. We try to get the vitamin E from natural sources; we do not use the synthetic pills because they are derived from petrochemical intermediates, and some believe that these preparations might be pro-oxidant as well as antioxidant. So we use extracts from wheat germ, usually 200 IU to 400 IU. We also include B-complex vitamins, selenium, and other minerals. Herbal Treatments for Antiretroviral or IL-2 Effects Dr. Joshi: We are also using certain herbal medications -- some of which increase the body's natural production of IL-2. We presented a poster on this approach in 1998, at the 12th World AIDS Conference in Geneva ["Effect of unique herbal formulation in Indian HIV patients: A pilot study," 12th World AIDS Conference, Geneva, June 28 - July 3, 1998, abstract #42385]. We have compiled an herbal booklet, listing each ingredient, with references to studies showing antiviral activity, or increases in the natural production of IL-2. De-Worming, and Other Treatment for Intestinal Inflammation Dr. Joshi: We are also giving a weekly dose of albendazole to patients who have intestinal parasites. We have seen that if we de-worm patients routinely, after six months to a year there is a reduction of viral load. Indian patients traditionally have higher viral set points than European patients; this might be related to the parasites. Deworming might assist mucosal immunity in the gut, and improve the CTL response against HIV. Also, in a couple of patients, I am trying mesalamine, a drug used to reduce intestinal inflammation. Side Effects of Antiretroviral Regimens Dr. Joshi: We have not had problems with mitochondrial toxicity -- perhaps because of our nutritional therapy, or perhaps because we do not have ddI in India. I also believe that immunonutrition helps to some extent with lipodystrophy. But we are seeing lipodystrophy. And we are also seeing other side effects which have been reported elsewhere, including osteoporosis, and aseptic necrosis of the femur, in people on protease-inhibitor regimens in India. So there is considerable concern about these drugs, and we are looking at PI-sparing regimens. Nevirapine is now available in India, and we will be using it for this purpose. ***** Testosterone Cream Available at CPS; Gel Approved by FDA by John S. James On March 2 the Community Prescription Service, a mail- order pharmacy associated with POZ magazine and specializing in HIV, announced that it is selling a compounded testosterone cream. This product is not generally available in pharmacies. ("Compounded" means that it is specially prepared by a pharmacist at the direction of a physician, not a packaged pharmaceutical product; compounded products do not have to pass most of the FDA requirements for approval of pharmaceuticals.) Topical testosterone has long been available (see Testosterone Cream and Gel Available; Prices Vary Greatly," AIDS TREATMENT NEWS #307, November 20, 1998), but usually only through certain pharmacies which specialize in compounding. With the CPS product, the physician specifies the starting dose per application, and the cream is made up accordingly. According to CPS, for most people, an appropriate starting dose is 12.5 mg of testosterone per application. The same controlled-substance regulations apply to topical testosterone as to the injected or patch forms of the drug. For more information about this testosterone cream, call CPS at 800-842-0502. Note: On February 29 Unimed Pharmaceuticals, Inc. announced that the FDA had approved its AndroGel(TM) 1% testosterone gel "for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone" -- the first time the FDA has approved such a product. However, AndroGel is not expected to be widely available in pharmacies until mid summer. Apparently AndroGel will deliver a somewhat higher dose of testosterone than the CPS cream. Comment: We expect that the main practical difference between the products is that the AndroGel will be much more expensive. ***** Anabolics, Exercise, Nutrition, Supplements: New Book Available by John S. James BUILD TO SURVIVE, by AIDS treatment advocates Michael Mooney and Nelson Vergel, covering anabolic steroids, exercise, nutrition, and popular supplements (especially for preventing or treating HIV-related wasting), was published February 2000. Mooney and Vergel are also editors of the MEDIBOLICS newsletter, http://www.medibolics.com The book includes sections on AIDS wasting, BIA (bioelectrical impedance analysis), testosterone replacement therapy, different kinds of anabolic steroids, legality of anabolic steroids in medicine, lipodystrophy and potential approaches for management, side effects and guidelines for anabolic steroids, human growth hormone, orthomolecular nutrition, popular food supplements, various diet plans, food safety, diarrhea, blood tests to use before starting a nutritional program, exercise programs, recommended reading, references, and testimonials. BUILT TO SURVIVE is published by PoWeR (Program for Wellness Restoration), a nonprofit organization founded by Nelson Vergel. The cover price is $24.95, but copies can be ordered from the Houston Buyers' Club, 1-800-350-2392, for $18.95 +3.95 shipping; the book is also available through http://www.amazon.com , which can ship internationally. Comment BUILT TO SURVIVE provides an accessible overview of certain important therapies, by advocates who have made themselves experts in this area. Some of the recommendations may be controversial, and we are not qualified to judge their medical appropriateness. We suggest this book as a source of ideas that you may later want to discuss with your physician -- a discussion which the authors repeatedly urge their readers to have. ***** Vaccine News, March 2, 2000 Several major vaccine announcements were made on March 2, at a conference on the President's Millennium Vaccine Initiative in the White House: * The International AIDS Vaccine Initiative (IAVI) will invest $10 million this year to help fund the development of six HIV vaccine candidates for developing countries. IAVI, funded by foundations and governments, establishes partnerships with industry using a "social venture capital" approach: in return for investment, IAVI secures rights to ensure that a successful vaccine will be available to developing countries at a reasonable price. * Pharmaceutical corporations announced donations of millions of doses of existing vaccines to developing countries; four major companies promised to speed research and development of vaccines for AIDS and malaria, which currently have no vaccines. Also, Clinton has proposed a billion-dollar tax credit over ten years to speed development of vaccines for HIV, tuberculosis, and malaria, and a $50 million contribution for a global vaccine bank. * The U.S. National Institute of Allergy and Infectious Diseases released THE JORDAN REPORT 2000, on the state of development of vaccines for many diseases; 8 pages of the 173-page report summarize the current status of several current approaches to an AIDS vaccine, but other sections are also relevant. THE JORDAN REPORT 2000 is available at www.niaid.nih.gov; more information on NIAID's role in AIDS vaccines is at http://www.niaid.nih.gov/aidsvaccine * The Global Alliance for Vaccines and Immunization (GAVI) is a major government/industry/foundation alliance to get existing and new vaccines to poor countries. According to GAVI, vaccines save about three million children's' lives every year -- but almost three million other children die each year because they were not vaccinated. For more information, see http://www.vaccinealliance.org * New vaccine bills introduced in Congress: On March 1 Senator John Kerry (D., Massachusetts) and two others introduced the Vaccines for the New Millennium Act of 2000 in the Senate, and Representative Nancy Pelosi (D., San Francisco) and nine others introduced it in the House. [Rep. Pelosi had previously introduced the Lifesaving Vaccine Technology Act of 1999 to provide a tax credit for research and development of vaccines for HIV, tuberculosis, and malaria; President Clinton had instead proposed a fund to purchase these vaccines after they were developed, which incidentally would not cost the government money now. The new Kerry/Pelosi bill combines several ideas and includes both approaches.] ***** Fluconazole: Pfizer Asked to Lower Africa Price by John S. James On March 13 the Nobel prize winning medical organization Doctors Without Borders/Medicins Sans Frontiers (MSF) demanded that Pfizer, Inc. greatly reduce the price of fluconazole in poor countries, in a communication delivered to the company in 18 countries (Pfizer is headquartered in New York). Doctors Without Borders supported South Africa's AIDS-activist Treatment Action Campaign (TAC), which on the same day organized a delegation of union leaders, church leaders, and others representing millions of South Africans asking that Pfizer either lower the price, or grant a voluntary license allowing TAC to import the drug or manufacture it locally, with a 5% royalty to Pfizer. According to MSF, fluconazole costs almost 15 times as much in South Africa, where it is patent protected, than in Thailand, where it is not (in U.S. currency, $17.84 in Africa for an adult's daily maintenance dose, which must be taken indefinitely, vs. only $1.20 at the generic price in Thailand). The African price is more than twice the average daily wage of employed South Africans. The consequence is that few Africans are treated for cryptococcal meningitis, and as a result their life expectancy is less than one month. Patients who are treated can live for years with a greatly improved quality of life. Many Africans could be treated if they could obtain the drug at the generic price. According to TAC, Pfizer in South Africa agreed to respond within one week as to how TAC's letter was being handled -- although it could not act on the issue itself within a week, as the decision would have to be made in the United States. Letter from Archbishop The Most Reverend Njongonkulu Winston Hugh Ndungane, Anglican Archbishop of Cape Town, wrote the following to the chairman and CEO of Pfizer, Inc.: "Dear Mr. Steere, "In the face of evidence to the effect that it is possible to manufacture and sell Fluconazole at a price affordable to a significant number of South Africans, we urge you, in the interest of justice, to make this a reality. "We do understand that Pfizer is neither a charitable nor a humanitarian organization and that you have a responsibility to your shareholders. We assume, however, that Pfizer's market share in our country warrants an interest in our economic and social stability -- both of which are acutely threatened by our AIDS pandemic. "Many so called "First World" institutions and corporations are busy taking out patents on every new intellectual idea and discovery in every field. The poor are continually being excluded from benefits of these discoveries and will continue to be so until some sense of global responsibility is introduced. Creativity is needed to bridge the huge gap between human need, scientific effort and market returns. "Both rich and poor need to direct their attention towards a common plan of action regarding mobilization of science and technology for poor country problems. One recent suggestion is the creation of a vaccine fund which would guarantee future markets for epidemic vaccines. "Besides the bottom line issues, we strongly urge you to consider these humanitarian and moral aspects. "Grace and Peace," ***** Dietary Supplement Regulation: FDA Public Hearing April 4, Written Comments Due May 4 by John S. James On April 4 the FDA will hold a public hearing on regulation of claims for dietary supplements. While the technical issues involved do not directly affect AIDS treatment access, they are part of a larger issue which does. Anyone wishing to speak at this hearing must register in writing by March 28. But written comments can be submitted until May 4. The hearing is to get public input on how the FDA should change its regulations in response to a court case which it lost. An appeals court held that "the First Amendment [of the U.S. Constitution] does not permit FDA to reject health claims that we [FDA] determine to be potentially misleading unless we also reasonably determine that no disclaimer would eliminate the potential deception" [FDA's summary in the FEDERAL REGISTER, March 16]. For background and more information, see "Food Labeling; Dietary Supplement Health Claims; Public Meeting Concerning Implementation of Pearson Court Decision and Whether Claims of Effects on Existing Diseases May Be Made as Health Claims," FEDERAL REGISTER, March 16, 2000 [page numbers not available as this article goes to press]. Comment The larger issue is the regulation of "dietary supplements," such as the herbal products which are widely sold in the U.S. in health-food stores, and now in mainstream drugstores as well. There is widespread agreement that more regulation is needed than exists today. The appropriate kind of regulation is unclear. The danger is that we will get the wrong kinds of regulation, just because the models are most readily available. If natural products become regulated like pharmaceutical drugs, most will be effectively banned since no company will pay for the large clinical trials which would be necessary for approval. Even worse is the war-on-drugs model, which for decades has had a major impact on medicine in denying appropriate pain relief, because doctors reasonably fear trouble even when their prescribing is entirely legitimate and legal. The drug war has also greatly hindered the appropriate use of anabolic steroids in treating wasting, which causes many AIDS deaths -- and greatly impeded the use of needle exchange, although it has been clearly shown to prevent HIV infection without increasing drug use. Fortunately there are more positive regulatory models from some European countries -- which have long allowed the sale of a large variety of natural products at reasonable prices, under effective but not prohibitive controls. The U.S. is prone to destructive "moral" crusades -- which is why we have both the drug war, and the new mass imprisonment of the last 20 years. Because of the difficulty of making anything happen, this destructive spirit may be used as an ally by persons and institutions seeking legitimate safety measures for natural health products. Anyone interested in access to inexpensive or natural treatments should be paying attention at this time. ***** FDA Drug-Approval Background: New Web Pages by John S. James The FDA recently launched an excellent Web site with detailed release: The information includes: -Drug Approval Application Process. An overview from test tube to marketing -Investigational New Drugs. Includes emergency INDs, FAQs, etc. -New Drug Applications -Generic Drug Applications -Electronic Submissions -Small Business Assistance Program. Includes funding sources and orphan drugs. -Post Drug Approval Activities. Includes advertising, medication errors, drug shortages and surveillance activities. Treatment activist Brenda Lein of Project Inform said, "The information is absolutely wonderful and I'd encourage any treatment activist who isn't clear about the FDA and their process to read through the materials and become familiar with the drug discovery and development process... [including] why companies conduct certain tests based on what the FDA requires of them, and why other tests may not be conducted." The FDA site is at http://www.fda.gov/cder/regulatory/applications/default.htm ***** African Americans and AIDS: Highlights of 2nd Annual Washington Conference by Al Cunningham African Americans have access to modern HIV treatment, but far too many have not been tested and are not receiving medical care, according to speakers at the 2000 National Conference on African-Americans and AIDS, February 24 and 25 in Washington, D. C.; racism, sexism, homophobia, stigma associated with HIV and AIDS, lack of trust in the healthcare system, and lack of access to healthcare, remain major barriers. The two-day conference, sponsored by Johns Hopkins University School of Medicine and Bristol-Myers Squibb, was the second annual meeting on African Americans and AIDS, with talks by leading researchers, public health officials, and non-government activists. Some highlights: * Long-term survivor Phill Wilson, who opened the meeting, later noted that 50% of the new AIDS cases among men who have sex with men are now men of color. "The tragedy is that this did not have to happen. Men of color were disproportionately impacted in 1989 when they were 30% of AIDS cases among men who have sex with men. The question now is what are we going to do at this time?" Wilson is a gay African American activist and founder of the African American AIDS Policy and Training Institute, http://www.AAAinstitute.org * U.S. Health and Human Services Secretary Donna Shalala described the Clinton Administration strategy as 3-fold: to put needed money into communities; to prevent the spread of HIV, and to eliminate barriers to care. "Too few African Americans are getting tested or getting access to care. The cost of treatment is high. The regimen of pills is difficult to follow. And prevention messages have not been targeted enough -- or become accepted enough -- in the African American community." * Human-rights leader Jesse L. Jackson Sr. called for visible African Americans to model the importance of testing -- followed by his own public test at a local HIV clinic for African Americans. * John G. Bartlett, M. D., from Johns Hopkins, discussed the government guidelines for HIV treatment, most recently updated January 29 (see "New Guidelines for HIV Treatment; Resistance Testing Now Recommended," AIDS TREATMENT NEWS #337, February 18, 2000). Dr. Bartlett also cited some of the long-term consequences of the HAART combinations, including elevated triglycerides and cholesterol levels, fat accumulation and fat wasting (lipodystrophy), insulin resistance or diabetes, and other disorders. He suggested that it is too soon to generalize about the benefits and risks of early HAART therapy. * Anthony S. Fauci, M. D., Director of the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health, emphasized that while the guidelines are important, they do not mean that everyone must be treated -- and patients' rights to choose not to be treated should be respected. Dr. Fauci also noted that globally, 90% to 95% of people who need antiretroviral treatment will never get it. He referred the audience to http://www.hivatis.org for the latest updated version of the treatment guidelines. * Robert C. Gallo, M. D., discussed the search for biological treatments for HIV infection, which could be nontoxic and inexpensive. His talk included beta chemokines, and also the role of tat in HIV infection and immune suppression. His group is developing a tat toxoid which might be useful in both treatment and/or vaccination against HIV. Full audio and slide presentations should be available by April at the Johns Hopkins Web site, http://www.hopkins- aids.edu ***** 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: Phillip T. Alden Statement of Purpose: AIDS TREATMENT NEWS reports on experimental and standard treatments, especially those available now. We interview physicians, scientists, other health professionals, and persons with AIDS or HIV; we also collect information from meetings and conferences, medical journals, and computer databases. Long-term survivors have usually tried many different treatments, and found combinations which work for them. 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ISSN # 1052-4207 ***** How to Subscribe Call 800-TREAT-1-2 (800-873-2812), or 415-255-0588. AIDS TREATMENT NEWS is published 24 times per year, on the first and third Friday of every month, and print copies are sent by first class mail. Email is available (see below). Annual Rates: business/professional $270; nonprofit community organization $135; individual $120 ($70 for 6 months). Email: Priority Email Delivery. Business, nonprofit and full- rate individual subscribers can receive a copy by email, in addition to their regular print copy, at no extra charge. These email copies are sent before the printed copies are mailed. Email: Free Delivery for Individuals (delayed one week). To subscribe, send email to aidsnews@aidsnews.org with "subscribe" in the title or first line. Back issues are available at http://www.aids.org/atn Copyright 2000 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used. -- John S. James, AIDS Treatment News aidsnews@aidsnews.org http://www.aidsnews.org &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display