Date: Mar 17 2000 (712 lines) 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: email@example.com 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 firstname.lastname@example.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 email@example.com http://www.aidsnews.org
by Anthony Brink
To overturn orthodoxy is no easier in science than in philosophy, religion, economics, or any of the other disciplines through which we try to comprehend the world and the society in which we live.
– Ruth Hubbard US biologist b.1924
Considering how AIDS saturates our public discourse, galvanises our politicians, thrills our gee-whiz journalists, inspires our musicians, worries our clergy, agitates our AIDS-activist lawyers, perturbs the judges of even our highest court, engages the South African Law Commission’s energies in cooking up imaginative new bills, dominates our medical research effort, infuses exciting new relevance into tired careers in virology departments, and siphons off our tax rands into the pockets of our condom missionaries and ‘AIDS counselors’ proselytizing indefatigably to a stubborn public, your regular guy might be excused for believing that our country and the world were in the throes of a dire public health crisis, a new Black Death, and for thinking that the fact of it was as certain as any in science about which there obtains a universal consensus.
In fact, hundreds of scientists of the highest rank disagree with the HIV-AIDS causation hypothesis. They think ‘AIDS’ as a medical construct is a passing fad, a fashionable new name for age-old ills, and that boiled down, AIDS is just money spinning political kitsch. In their most assiduous dissents they emphasize that ‘HIV’ has never been isolated under the well-settled rules for viral isolation, assert that ‘HIV’ has never been shown to exist as an infectious entity of exogenous origin, and demonstrate that every protein claimed uniquely to be constituent of ‘HIV’ is actually cellular, not viral – in other words, that all HIV-positive test results are false positives. In short, they consider the HIV-AIDS paradigm a scientific blunder of biblical proportions, and its experts foolish quacks. These AIDS dissidents include professors emeriti at the pinnacle of their specialities in cell-biology, virology and related fields. They also include leading mathematicians, actuaries, and law and history professors. Among them are two exceptionally distinguished Nobel laureates in our time, Walter Gilbert (Chemistry 1980), and the Einstein of modern biology, Kary Mullis (Chemistry 1993).
Dr Peter Duesberg, professor of cell-biology, University of California at Berkeley, member of The National Academy of Sciences: Before Duesberg’s wrecking-ball challenge to Gallo’s HIV-AIDS theory was published as an invited paper in the prestigious journal Cancer Research in 1988, Gallo had observed, “No one knows more about retroviruses than Peter Duesberg.” Once acclaimed as a widely published and extensively cited Nobel candidate, but now ‘delegitimated’ as a scientist, Duesberg was the recipient of the largest annual research grant in biology for years – awarded for the pursuit of whatever avenue of scientific enquiry took his fancy. Stripped of his grant and his post-graduate classes, practically barred from researching and publishing, and reduced to chairmanship of his faculty’s annual picnic committee, he continues to point out the fundamental anomalies, deficiencies and paradoxes of the 15 year old theory that the 29 old diseases renamed AIDS in the presence of HIV antibodies could have any causal link to a retrovirus. However, Duesberg finds himself increasingly alone in the AIDS dissident camp too, eclipsed by Eleni Papadopulos-Eleopulos et al (below) whose more fundamental tack in impeaching the HIV-AIDS theory is winning over its best heterodox scientists, most recently, Kary Mullis (below), pathology and epidemiology specialist Gordon Stewart (below), and Etienne de Haarven, pathology professor emeritus at Toronto, renowned for his published work in the electron photomicrography of viruses.
Eleni Papadopulos-Eleopulos, bio-physicist, department of medical physics, Royal Perth Hospital, Australia: Collaborating with, among others, John Papadimitriou, a practicing pathologist and professor at University of Western Australia’s medical school, David Causer, senior physicist, head of the department of medical physics and professor at Royal Perth Hospital, and Valendar Turner, consultant emergency physician at the Royal Perth Hospital, Papadopulos-Eleopulos has raised the most radical and dramatic challenges to the HIV-AIDS theory, by highlighting the lack of a proper gold standard for the HIV antibody tests, in that unlike other known viruses, HIV has never been isolated according to the classical procedure for the isolation of viruses, often referred to as the Pasteur Rules.
Dr Walter Gilbert, formerly molecular-biology professor at Harvard: One of contemporary science’s most outstanding and accomplished scientists, Gilbert won his Nobel for inventing the now foundational modern technique for DNA sequencing. He considers Duesberg to be “absolutely correct in saying that no one has proven that AIDS is caused by the AIDS virus. There is no animal model for AIDS, and without an animal model, you cannot establish Koch’s postulates (to prove the role of the suspected pathogen).” He observes, “The community as a whole doesn’t listen patiently to critics who adopt alternative viewpoints. Although the great lesson of history is that knowledge develops through the conflict of viewpoints.”
Dr Kary Mullis, molecular biologist: Nobel winner Mullis’ watershed invention of the Polymerase Chain Reaction technology for amplifying minute DNA fragments for identification has so revolutionised biology that one might fairly speak of two epochs, the dark ages before and the enlightenment after it. He deplores the misapplication of his invention to measure “HIV viral load.” He predicts that, “Years from now, people will find our acceptance of the HIV theory of AIDS as silly as we find those who excommunicated Galileo.” Endorsing Duesberg’s rejection of the orthodox model of infectious AIDS, he says, “As applied, the HIV theory is unfalsifiable, and useless as a medical hypothesis I can’t find a single virologist who will give me references which show HIV is the probable cause of AIDS. If you ask…you don’t get an answer, you get fury.” The HIV-AIDS hypothesis, he thinks, is “one hell of a mistake.”
Dr Harry Rubin, retrovirologist, professor of molecular biology, University of California at Berkeley, member of National Academy of Sciences: “I don’t think the cause of AIDS has been found. I think (that in) a disease as complex as AIDS there are likely to be multiple causes. In fact, to call it a single disease when there are so many multiple manifestations seems to me to be an oversimplification.”
Dr Richard Strohman, emeritus professor of cell-biology, University of California at Berkeley: The HIV-AIDS hypothesis is “bankrupt.”
Dr Beverly Griffin, director and professor of virology, Royal Postgraduate Medical School in London: “I do not believe HIV, in and of itself, can cause AIDS.”
Dr Gordon Stewart, emeritus professor of epidemiology, University of Glasgow, and former AIDS advisor to the World Health Organisation: “AIDS is a behavioural disease. It is multifactorial, brought on by several simultaneous strains on the immune system – drugs, pharmaceutical and recreational, sexually transmitted diseases, multiple viral infections… there is no specific etiologic agent of AIDS… the disease arises as a result of a cumulative process following a period of exposure to multiple environmental factors… Nobody wants to look at the facts about this disease. It’s the most extraordinary thing I’ve ever seen. I’ve sent countless letters to medical journals pointing out the epidemiological discrepancies and they simply ignore them. The fact is, this whole heterosexual AIDS thing is a hoax.”
Dr Albert Sabin, discoverer of live-virus polio vaccine, National Institutes of Health: “The basis of present action and education is that everybody who tests positive for the virus must be regarded as a transmitter and there is no evidence for that.”
Dr Bernard Forscher, former managing editor of the journal, Proceedings of the National Academy of Sciences: “The HIV hypothesis ranks with the ‘bad air’ theory for malaria and the ‘bacterial infection’ theory of beriberi and pellagra (caused by nutritional deficiencies). It is a hoax that became a scam.”
Dr Simon Wain-Hobson, immunologist, Institut Pasteur, France: “… an intrinsic cytopathic effect of the virus (HIV) is no longer credible…”
Dr Alfred Hassig, immunologist, former emeritus professor of immunology, University of Bern, and former director of a Swiss blood transfusion laboratory: “The sentences of death accompanying the medical diagnosis of AIDS should be abolished.”
Sir John Maddox, editor, Nature Magazine: “(Luc) Montagnier said clearly what he meant. HIV (alone) is… not… a sufficient cause of AIDS.”
Dr Fabio Franchi, specialist in infectious diseases and preventive medicine, Trieste, Italy: “I am not an agnostic. I am well convinced HIV is harmless.”
Dr Charles Thomas, former professor of molecular biology at Harvard and Johns Hopkins universities: “It is widely believed by the general public that a retrovirus called HIV causes the group of diseases called AIDS. Many biomedical scientists now question this hypothesis. We propose that a thorough reappraisal of the existing evidence for and against this hypothesis be conducted by a suitable independent group.” He himself has no doubts. He rejects the HIV-AIDS hypothesis as a “fraud”.
Dr Phillip Johnson, senior professor of law, University of California at Berkeley: “The establishment continues to doctor statistics and misrepresent the situation to keep the public convinced that a major viral pandemic is under way when the facts are otherwise.”
Dr Serge Lang, professor of mathematics, Yale University and member of the National Academy of Sciences: “There does not even exist a single proper definition of AIDS on which discourse or statistics can reliably be based… the CDC calls these diseases AIDS only when antibodies against HIV are confirmed or presumed to be present. If a person tests HIV negative, then the diseases are given another name I do not regard the causal relationship between HIV and any disease as settled. I have seen considerable evidence that highly improper statistics concerning HIV and AIDS have been passed off as science, and that top members of the scientific establishment have carelessly, if not irresponsibly, joined the media in spreading misinformation about the nature of AIDS.”
Dr Joseph Sonnabend, South African born New York physician: “The marketing of HIV, through press releases and statements, as a killer virus causing AIDS without the need for any other factors, has so distorted research and treatment that it may have caused thousands of people to suffer and die.”
Dr Harvey Bialy, editor of the science journal Nature Bio/Technology: “From both my literature review and my personal experience over most of the AIDS – so called AIDS centres in Africa, I can find absolutely no believable persuasive evidence that Africa is in the midst of a new epidemic of infectious immunodeficiency.”
Dr Charles L. Geshekter, professor of African History, California State University: … From “Cameroon to California, sex education must no longer be distorted by terrifying, dubious misinformation that equates sex with death… African poverty, not some extraordinary sexual behavior, is the best predictor of AIDS-defining diseases… A 1994 report in the Journal of Infectious Diseases concluded that HIV tests were useless in central Africa, where the microbes responsible for tuberculosis, malaria, and leprosy were so prevalent that they registered over 70% false positive results…in people whose immune systems are compromised for a wide variety of reasons other than HIV…”
Dr Hiram Caton, ethicist, head of the School of Applied Ethics at Griffith University, Brisbane, Australia: “The AIDS epidemic was a mirage manufactured by scientists who believed that integrity could be maintained amidst the diverting influences of big money, prestige and politics.”
Dr Ralph Moss: author of The Cancer Industry: “The paradigm that was laid down for how to milk the cancer problem is basically the same paradigm which is being followed in milking the AIDS problem.”
Dr Frank Buianouckas: professor of mathematics, Bronx New York: “I suspect everything involved in this AIDS epidemic. If HIV causes anything, it certainly causes fund-raisers. It sells stocks. It supports dances. It sells condoms. And it keeps the AIDS establishment going.”
Questions of safety and utility.
Adv Anthony Brink of the Pietermaritzburg Bar discusses AZT with Dr Desmond Martin, Deputy Director of the National Institute for Virology in Johannesburg and Director of its AIDS Unit, and President of The Southern African HIV-AIDS Clinicians Society. Dr Martin serves as virology consultant on the editorial board of the AIDS journal AIDS Bulletin, published by the South African Medical Research Council, and is Co-Chair of the Scientific Programme (Basic Sciences) for the XIIIth International AIDS Conference to be held in Durban in July 2000.
On 17 March 1999, my critical essay AZT: A Medicine from Hell was published in The Citizen, a daily newspaper distributed nationally in South Africa. Its sardonic tone and polemical style were contrived to stimulate a public debate of hitherto unexamined issues in the current controversy in South Africa concerning the provision of AZT to rape victims and HIV-positive pregnant women, for which AIDS activists, journalists, opposition politicians, doctors and health workers have been agitating strenuously.
South Africa’s leading AIDS authority, Dr Desmond Martin rose to the piece and mounted a rebuttal on 31 March entitled AZT: A Medicine from Heaven.
My rejoinder AZT and Heavenly Remedies was printed the following day. It has since been substantially revised, extended and updated, and includes mention of several papers appearing in the journalsClinical Infectious Diseases, New England Journal of Medicine, Nature Medicine, AIDS, the Journal of Medical Virology, The Lancet, Mutation Research, the Journal of the American Medical Association and Current Medical Research and Opinion between April and September 1999.
Dr Martin’s off-topic contentions are addressed in an appendix to my reply, available on request.
At my instance, NOSEWEEK – edited and published by South Africa’s most accomplished and respected investigative journalist, Martin Welz – will be covering AZT in a forthcoming edition, according to notices appearing in both its November 1998 and May 1999 issues.
Updated to 18 October 1999
AZT: A Medicine from Hell
The more ignorant, reckless and thoughtless a doctor is, the higher his reputation soars, even amongst powerful princes.
Desiderius Erasmus (c. 1466-1536), Dutch humanist.
Praise of Folly, ch. 33 (1509).
National Health Minister Nkosazana Zuma has been condemned by just about everyone recently for her heartless decision not to make a drug called AZT available at state expense to HIV-positive pregnant women. It reduces the risk, so its said, of the transmission of HIV from mother to child. Politicians and journalists from left to right have joined moist-eyed, hand-wringing doctors pleading for the free provision of AZT to these women, their babies cruelly deprived and doomed to die, they say.
In all the fuss about the ministers decision on AZT, no-one seems to have stopped to ask, “So what the hell is this stuff anyway?”
In 1964, a chemist, Jerome Horwitz, synthesized a sophisticated cell poison for the treatment for leukaemia*. He called it Compound S. Its formal title is 3-Azido-3-deoxythymidine, or Azidothymidine for short, but everyone knows it by its nickname, AZT.
It works like this. Thymidine is one of the four nucleotides (building blocks) of DNA, the basic molecule of life. AZT is an artificial fake, a dead ringer for thymidine. As a cell synthesizes new DNA while preparing to divide in order to spawn another, AZT either steals in to take the place of the real thing, or else disrupts the delicate process by interfering with the cells regulation of the relative concentrations of nucleotide pools present during DNA synthesis. Thats the end of the cell line. Cell division and replication, wrecked by the presence of the plastic imposter, comes to a halt. Chemotherapeutic drugs such as AZT are described as DNA chain terminators accordingly. Their effect is wholesale cell death of every type, particularly the rapidly dividing cells of the immune system and those lining our guts. Horwitz found that the sick immune cells went, but with so many others that his poison was plainly useless as a medicine. It was akin to napalm-bombing a school to kill some roof-rats. AZT was abandoned. It wasnt even patented. For two decades it collected dust forgotten – until the advent of the AIDS era.
As soon as Dr Robert Gallo made his famous press-conference announcement on 23 April 1984 that his virus was the probable cause of AIDS, the race was on to find a pharmaceutical weapon against it. The stratospheric profit potential (since borne out) of the first to the post was on everybodys mind. Obviously, if an already synthesized drug could be applied to the malady, it would short-cut most of the road-race there. AZT was fished off the shelf, along with numerous other abandoned brews, and put to some in vitro tests. It demonstrated a bright alchemical sparkle. On the basis of a reassuring but fallacious assertion that AZT was specifically antagonistic to HIV, and a thousand times more toxic to the latter than human cells generally, the drug went to clinical trials. The chaos that the trials degenerated into is a tale too long to tell here. It wouldnt be extravagant to call them fraudulent. At best, they were so incompetently staged that the data gathered under them were useless, save to note that many of its subjects taking AZT needed repeated blood transfusions to keep going. Small surprise, since AZT was designed specifically to kill blood cells; the label (bearing skull and cross-bones) on laboratory supplies cautions, “Toxic by inhalation, in contact with skin and if swallowed. Target organ(s): Blood, bone marrow Wear suitable protective clothing.”
Four months after the trial started, it was prematurely called off, on an interpretation of the provisional results deemed positive for the drug by the trial overseer. Next, it went before the FDA, to be approved in record time under huge pressure from gay lobbyists. Strong reservations were expressed at the hearing about its dreadful toxicity. The chairmans vote against was defeated. As the most poisonous drug ever licensed by the FDA for indefinite use, and with the conviction apparently that the terrible new disease needed a terrible medicine, AZT was approved for use in extreme AIDS cases only – for which you might want to read, in cases of people very ill with their presenting AIDS indicator disease, fungal pneumonia or what have you. It wasnt a year later, in the orgy of stupidity that characterises the AIDS age, that AZT was officially recommended for administration to entirely healthy people unfortunate to ring positive to an HIV antibody test. Since the drug destroys the very immune cells allegedly attacked by HIV, the introduction of AZT as a treatment regimen for asymptomatic HIV positive people saw the AIDS mortality rate among the previously well take off like a rocket. Five years and countless deaths later, and only after the disastrous results of the Concorde trials in Europe and St Mary trials in the US had come in, was this murderous treatment recommendation reversed. AZT, it was found, did no good. Of course not. On any intelligent consideration of its pharmacological action, AZT could never in a million years be anti-viral, any more than arsenic could have cured the scurvy for which it was administered to sailors, and later, to troops in the trenches in the First World War.
In Europe and the US, HIV-positive long term survivors quietly gather to form groups, having sloughed off the terror of the death sentences passed on them by their doctors. Heres the strangest thing. Without exception, what they find they all have in common is that they all eschewed (or quickly gave up) AZT, related nucleoside analogues like 3TC, and protease inhibitors. Some have pondered the unthinkable: that nearly all medically managed AIDS cases, always terminal, represent that balefully familiar phenomenon in the history of medicine, iatrogenicide – to be killed by the cure. Their reasoning looks less obscure when one reads the AZT package insert. To do so might tempt one to wonder impertinently whether AZT wasnt AIDS by prescription. Indeed, such perverse conjecture is actually confirmed in capitals: AZT use “MAY BE ASSOCIATED WITH HEMATOLOGIC TOXICITY INCLUDING GRANULOCYTOPENIA AND SEVERE ANEMIA” (destruction of white and red blood cells respectively), and “PROLONGED USE OF RETROVIR HAS BEEN ASSOCIATED WITH SYMPTOMATIC MYOPATHY (gross atrophy of muscle tissue) SIMILAR TO THAT PRODUCED BY HUMAN IMMUNODEFICIENCY VIRUS”. As to the latter alibi, history will judge whether the thousands of healthy HIV-positive people who embarked on their metabolic poison treatment and wasted away (as the AZT insert predicted) would have died had they ignored doctors orders and thrown their pills away. Here the syphilis story is instructive.
Before the introduction of mercury and arsenic salts as a treatment for this clap, the organic brain damage and dementia that signaled tertiary- or neuro-syphilis was quite unknown to medicine, and then disappeared when penicillin replaced the older decoctions. The moral is hard to miss.
One sane notion in that otherwise mad dance with death that chemotherapy for cancer involves is that you stop before you drop. Since healthy cells are always killed in the crossfire, the idea is to rescue the patient from going over the cliff along with the target bad cells, by taking him off the drug in the nick of time. That iron rule is broken in AIDS treatment. Youre going to die, youre told, so better take the bitter medicine to the bitter end, to stave off the evil day. But as AZT heads like a heat-seeking missile for ones immune and energy transporting cells (“target organs: blood, bone marrow”, remember?) dying of AIDS on AZT is a racing certainty. No one has ever been cured by AZT, but it sells like hot cakes all the same, still the most widely prescribed AIDS drug, and it reaps profits counted in billions of pounds.
Ever irrepressible as a medicine following one failure after another, in 1994 AZT was proposed as a treatment for pregnant women to prevent the transmission of HIV from mother to child, or so it was touted. Until then, it had been staunchly contraindicated during pregnancy. Generously underwritten by the drugs manufacturer, the study, ACTG 076, in which this startlingly novel use of AZT was tried, epitomises the junk-science that characterises so much AIDS research. Of 477 babies born to HIV-positive mothers in the trial, 13 in the AZT-treated group were born antibody-positive, against 40 in the placebo group. Apart from the lunacy of basing a decision on such feeble numbers to dose HIV-positive mothers with a cell-toxin as lethal as AZT, the underlying assumption that an HIV-positive test result predicts inevitable illness and death is a canard of modern medicine which, surprisingly, wants for evidence. Most babies seroconvert to HIV-negative in any event, medicated or not. The other overarching myth is that the mere presence of antibodies in ones bloodstream signifies an active infection. Isnt it elementary that we carry antibodies to all sorts of pathogens that we have met and defeated? Isnt this first-year stuff? AZT advocates confess to being completely in the dark to account for the vaunted HIV blocking effect they claim. The reason why vitamin A administered instead works precisely the same magic might be a pointer to something less interesting: stressed health, thanks to chronic poor nourishment and living conditions. As for the positive immune signals a short course of AZT can generate, poison ingestion provokes an immune reaction as the body rises to the insult. This is old hat.
Thrown to the wind have been all the safeguards set up to ensure that the Diethylstilbestrol and Thalidomide tragedies would never happen again. Before the hysteria of the AIDS age, women were enjoined even to avoid drinking beer whilst pregnant. A recently reconfirmed active carcinogen, and teratogen too – cells not killed outright are nastily maimed – AZT freely crosses the placental barrier, so the package insert tells us cheerfully. Has anyone here paused to question whether a growing foetus comprising rapidly dividing cells should be exposed to a random terminator of DNA chain synthesis? Apparently not. Certainly not the recipients of Glaxo-Wellcomes largesse from its slush fund of millions for those who make AIDS their business in this country. Nor our doctors carrying out bold medical experiments on the foetuses of pregnant black women – whose unlucky dice gives them a positive registration to the irredeemably and hopelessly non-specific HIV antibody test. Of course anyone in the game crying foul, and drawing attention to the reams of literature in the medical journals about the harm AZT causes – especially to the young, is going to find himself sent off and defunded, for keeps. (Were it not for the amazing collapse of critical intelligence in the AIDS age, Glaxo-Wellcomes heart-warming contributions to the fight against AIDS, with its research grants and cut-prices – described by the Mail and Guardian as a “bouquet of assistance” – might have been seen less as philanthropy than commerce, pure and simple. As it has achieved so successfully abroad, what better way to fix its local market than by buying off our medical establishment and AIDS activist crowd with lolly aplenty to fund their risible projects? And by baiting our government with current discounts for its rancid wares, in order to hook longer-term contractual commitments.)
The AIDS Law Project at Wits currently busies itself with plans to sue the minister in the High Court for an order compelling her to respect pregnant womens rights to AZT, and dole it out on the house. Then again, its AIDS activist lawyers gratefully take junkets to AIDS conferences in holiday cities overseas at Glaxo-Wellcomes expense. The human rights they pursue might be better served were these legal crusaders to call off their foolish case and think of ways best to bite the hand that feeds them: several actions for loss of support have been launched against Glaxo-Wellcome in England and the USA, arising out of the deaths of family members killed by their doctors prescriptions of AZT.
Although she has explained her perplexing decision on AZT on the basis of financial considerations exclusively, saying she would rather spend her money on AIDS education, one day Health Minister Nkosazana Zuma will be praised for her great prescient wisdom in keeping AZT away from pregnant women and their foetuses. A bit like much-lauded Dr Francis Kelsey, whom Kennedy honoured for her wise perspicacity in sparing the USA the European Thalidomide calamity, when in truth her only notable trait was her fortuitously inefficient foot-dragging in obstructing the start of the FDA approval process.
Its high time that all involved in this nightmarish mess go off and do some basic homework in the subject in which they have so much to say for themselves.
To a colleague, his widow and his son.
*Horwitz, J.P., Chua, J. and Noel, M: Nucleosides. V. The monomesylates of 1-(2-Deoxy-beta-D-lyxofuranosyl)thymine, Journal of Organic Chemistry 29: 2076-2078 (1964). An American biochemistry professor with whom I have corresponded privately and who prefers both to remain anonymous and not to upset the settled history – based on the first to publish – makes a documented prior claim to the first synthesis of AZT in the autumn of 1961.
Back to the top of this page now.
AZT: A Medicine from Heaven
Desmond J Martin
THE Southern African HIV/AIDS Clinicians’ Society responds to an article AZT: A Medicine from Hell, by Anthony Brink, published in The Citizen on March 17.
Human Immunodeficiency Virus (HIV) disease is a major global health problem and is associated with a significant morbidity and mortality.
The number of people infected with HIV is rapidly increasing; recent estimates indicate more than 30 million adults and 1,1 million children are infected worldwide. In South Africa it is estimated that in excess of three million people are infected. It has been predicted that 40 million persons, including four to five million children, will have acquired the infection by the year 2000. Mother-to-child transmission, the major cause of HIV infection in infants, has led to a 30 percent increase in the mortality rate of infants and children in recent years.
The introduction of highly active anti-retroviral therapy (HAART) has been good news. In the US the age-adjusted death rate among people with HIV in 1997 was less than 40 percent of what it was in 1995. This experienced was mirrored in other Western nations where dramatic declines in morbidity and mortality as a result of the increasing use of combination anti-retroviral therapy has occurred; many of these regimens contain AZT.
When AZT and other nucleoside analogues were first introduced they were used as monotherapy (a single drug was used). Clinical experience quickly showed that the effect of a single drug was short-lived, as resistance to the drug developed. It was then shown that by using a combination of drugs, a more lasting effect was obtained.
An added advantage of combination therapy was that the drugs acted at different stages of the replication cycle of the virus. This option therefore made sense; the risk of drug resistance was drastically reduced and long-lasting beneficial effects have been recorded. AZT together with 3TC and a protease inhibitor is a combination that has been found to be highly effective.
Impaired quality of life associated with the progression of HIV disease has a profound effect on the patient and leads to an increase in the direct medical and non-medical costs of illness. Published studies have shown that patients on combination therapy with AZT and 3TC have been able to maintain or more importantly improve their quality of life.
So effective are combination anti-retroviral regimens in reducing the complications of the disease that there are anecdotal reports emanating from the US that Aids wards are being emptied of their patients and in some instances wards have been closed. Clinicians are now treating patients in out-patient settings and the status of the disease has changed to that of a chronic manageable disease.
It is however, in the arena of prevention of HIV infection that AZT has produced dramatic results.
Worldwide, approximately 500 000 infants become infected each year as a result of mother-to-child transmission. In some African countries 25 percent of pregnant women are infected with HIV. Without preventative therapy up to a third of their babies may become infected; many of these children will die in their early years.
In 1994 a clinical trial conducted in the US and France (ACTG 076) demonstrated that AZT given to mothers during their pregnancies, intravenously during labour and orally to their babies for six weeks reduced the risk of mother-to-child transmission by 67 percent. This regimen has been adopted as the “standard of care” in the US.
However, it is unsuitable for developing countries because of its complexity and cost.
To address the problem the Ministry of Health in Thailand introduced a trial of simpler and less expensive regimens of AZT to prevent mother-to-child transmission. This trial showed that a simpler regimen of AZT given orally to mothers in the last weeks of pregnancy reduced the risk of transmission by 50 percent. This short course AZT regimen (so-called Thailand regimen) is much more suitable for developing countries than the US-protocol because it is much easier to administer and less costly ($50 v $800).
Preliminary data from United Nation Aids Programme (UNAids)- sponsored studies have also demonstrated that even more abbreviated, affordable, AZT-containing regimens may be equally effective.
Another instance where preventative AZT therapy is commonly used is in the event of a health-care worker (HCW) sustaining an occupational exposure to blood or body fluids from an HIV infected person (eg. needle-stick injury).
These occurrences are usually charged with much emotion and HCW’s are, quite justifiably, entitled to appropriate post-exposure prophylaxis to be commenced as soon as possible after the injury. A multinational study conducted among occupationally exposed HCW’s demonstrated a 79 percent reduction in the risk of acquiring HIV infection when AZT was used as post-exposure prophylaxis.
The toxicity of AZT is a very real issue however, the toxicity (particularly bone marrow toxicity) is usually noted in patients with advanced HIV disease whose bone marrow function may already be impaired by HIV disease. Toxicity does not appear to be a problem during short-term use (post exposure prophylaxis or mother-to-child transmission prevention).
Nevertheless vigilance and monitoring on the part of the clinician is necessary. If toxicity occurs the drug should be stopped and other drugs substituted and any appropriate management should occur. Toxicity in most cases is reversible. In addition, careful monitoring of babies whose mothers took AZT during pregnancy has failed to show any significant abnormal findings.
Thus AZT in combination with other drugs has proved to be invaluable for the treatment of those already infected with HIV and has also proved to be a potent preventative agent in the mother-to-child setting and for occupational exposures. For these very reasons the drug AZT deserves the accolade : AZT: a medicine from heaven.
Desmond J Martin is President of the South African HIV/Aids Clinicians Society.
Note: Dr Martin has no conflict of interest and has not received financial sponsorship from Glaxo-Wellcome.
AZT and Heavenly Remedies
What can you do against the lunatic…who gives your arguments a fair hearing and then simply persists in his lunacy?
Winston Smith, in Nineteen Eighty-Four
AZT – pure poison? Nonsense, retorts Dr Martin, with the avuncular bedside reassurance of Doctor who knows best. AZT, he proclaims, is God’s own medicine.
In his letter covering his response to my essay AZT: A Medicine from Hell, Martin rebukes the editor of The Citizen for his “gross irresponsibility” in publishing my piece without first having obtained the views of “the established experts.” In this reply, we’ll have a look at what experts from the top drawer of the AIDS research establishment have to say about AZT, the kind of guys who get to publish in the world’s most splendid medical and scientific journals.
True believer that he is, Martin sonorously praises “Highly Active Anti-retroviral Therapy” (HAART – cocktails of AZT and other metabolic poisons) as “good news” and “highly effective”, and even reports mass Lazarus cures with entire hospital wards closing down. Really? Not according to big-time AIDS clinician Dr Michael Saag of the University of Alabama, coeditor of ‘cutting-edge’ tomeAIDS Therapy just published in January. No dissident, he’s a paid consultant for AZT manufacturer Glaxo-Wellcome and other pharmaceutical corporations. In an interview in Esquire in April, he confesses that the HAART “‘dam’ is already leaking; there’s high danger of it collapsing altogether. Failures are occurring right and left.” He states plainly that doctors “should expect failure with whatever (HAART cocktail they) first use. We should plan on it. We should prepare for it. Clinicians should expect failure.” And failure they get.
Carr and Cooper wrote in The Lancet in December last year: “As the evanescent blush of success with so-called highly active antiretroviral therapy regimens begins to recede into the darkness…post-1996 AIDS conference hype (about) combination therapy including a protease inhibitor…(has come) back to haunt us.”
In April in the journal AIDS, Dr Steven Deeks and his colleagues at San Francisco General Hospital and the University of California, reported treatment failure for more than half their AIDS patients given HAART ‘triple-therapy’. Similarly, Medical Professor Dr Julio Montaner, head of AIDS Research at St Paul’s Hospital/University of British Columbia, Vancouver, and co-director of the Canadian HIV Trials Network tells us in the May issue of the Journal of the American Medical Association that, “Given the complexities and the increasingly recognized potential for long-term adverse effects of many of the currently available treatments, it is hardly surprising that (for) an alarmingly high proportion of patients…the failure (rate) has been in the order of 30% to 50% of patients at 1 year…”
Several other research papers published about AZT-based HAART in May and June all point a thumbs-down:
In May, in the New England Journal of Medicine, Zhang et al at the Aaron Diamond AIDS Research Center in New York report that following combination antiretroviral therapy “replication-competent virus can still be recovered from latently infected resting memory CD4 lymphocytes; this finding raises serious doubts about whether antiviral treatment can eradicate HIV-1… Six of the eight patients had no significant variations in proviral sequences during treatment…(and) it may require many years of effective antiretroviral treatment to eliminate HIV-1.” The researchers fret: “We are unable…to explain why drug-sensitive HIV-1 is capable of replicating at low levels during treatment with three or four drugs. But it is essential to the therapeutic effort that the answer, be it pharmacokinetic or cellular in nature, be obtained promptly.” Furtado and colleagues of the Northwestern University School of Medicine in Chicago and Los Alamos National Laboratory in New Mexico, reporting their research findings in the same issue, don’t beat about the bush so much: “HIV-1 infection cannot be eradicated with current treatments.” And Harrigan et al at St. Paul’s Hospital in Vancouver, British Columbia report in AIDS in May that in six patients with undetectable viral loads who gave up HAART “because of lipodystrophy, narcotic overdose, insomnia, and/or high blood pressure,” all experienced “HIV rebound…within 6 to 15 days…and approached or exceeded pretherapy (plasma HIV RNA) levels…within 21 days of stopping therapy.”
Commenting on these dismal findings, AIDS boss Anthony Fauci, Director of the National Institute of Allergies and Infectious Diseases in the US concedes with his characteristic up-beat gloss on yet another broken therapeutic promise, “What all these studies underscore is the pressing need to develop more effective, less toxic medications that can be used over the long term to suppress HIV, as well as novel strategies to then purge residual virus from the body and boost the immune system.” In plain English, this translates to an urgent need to find alternatives to AZT-cocktails because they are too poisonous and too ineffective to justify continued use.
In Nature Medicine in May, two other papers document how useless and harmful AZT-based ‘triple-therapy’ is. The first by Finzi et al at Johns Hopkins University Medical School tells the “depressing news” that “resting T-cells” said to be infected by HIV are impervious to HAART and appear to need a lifetime’s uninterrupted treatment – a regimen which the researchers point out is not feasible due to its toxicity. The second paper by Picker et al of the University of Texas Southwestern Medical Center suggests that patients on HAART need to take “vacations” from such medicine periodically, in view of their finding that HAART itself causes a reduction in their patients’ T-cell counts, and that patients suffer a significantly weakened immune capacity after such treatment. And in the May issue of AIDS, Ibanez et al at the Fundació irsiCaixa, Retrovirology Laboratory, Hospital Universitari Germans Trias i Pujol, in Barcelona, Spain report their findings “that 48 weeks of HAART does not significantly reduce the integrated HIV-1 proviral DNA load in the latently infected CD4 T cell reservoir.” In July, an article in The Lancet mentions a disappointing study just reported in Annals of Internal Medicine by Lucas et al at Johns Hopkins University School of Medicine. Of 273 patients given HAART over a two year period, only “23% of the cohort had fewer than 500 copies/mL HIV1 RNA in all three time intervals” during the trial.
Commenting ruefully on the Finzi and Zhang studies in the June issue of Nature Medicine, Saag and his colleague Michael Kilby at the AIDS Clinical Trials Unit, University of Alabama rub in the rude fact that HAART doesn’t work: “As (Zhang et al have) suggested, immediate attention should focus on the reasons why three- and four-drug potent anti-retroviral therapy does not completely suppress virus replication…even in the presence of undetectable HIV plasma RNA levels.”
In July The Lancet mentions a disappointing study just reported in Annals of Internal Medicine by Lucas et al at Johns Hopkins University School of Medicine. Of 273 patients given HAART over a two year period, only “23% of the cohort had fewer than 500 copies/mL HIV1 RNA in all three time intervals” during the trial.
AZT-based HAART has been said to prevent new rounds of infection by stopping HIV DNA from producing HIV RNA and thence the proteins and particles which AIDS experts identify as HIV. Since these latest research findings reveal that during HAART, the HIV viral burden – the amount of DNA provirus – does not alter, the “established experts” are confronted with small choice in rotten apples: either HAART isn’t anti-retroviral, or there is no relationship between HIV DNA and HIV RNA (which runs counter to a fundamental notion in the HIV theory of AIDS), or all that these cyto-toxic drugs do is hinder cells making RNA of any kind, or perhaps they just interfere in the measurement of whatever RNAs there are. Or all of the above. Take your lucky pick.
Current HAART research reports are reminiscent of the Pellagra plague in the US South over the first four decades of this century, for which Fowler’s Solution (arsenic) was the drug of choice. Heaps of impressive research articles were published in the medical journals regarding treatments for the germs causing this terrible disease, which affected millions and caused people to die in droves. It turned out the experts were all barking up the wrong tree. Everyone now knows that Pellagra is a disease of nutritional deficiency, and has nothing to do with germs. Pity about the quarantined patients in dozens of specially built pellagrin-hospitals who died of arsenic poisoning before the experts eventually changed their minds.
Writing in AIDS in 1997, Kelleher et al noted, “Lack of strong evidence exists for sustained immune reconstitution by current therapies (comprising AZT and other drugs, and AZT may) unmask silent opportunistic infections.” Like PCP. Pneumocystitis carinii pneumonia is a scarce disease, very difficult to diagnose accurately. It is caused by a ubiquitous fungal germ in just about all of our lungs. As a rule it only takes over, often together with esophageal candidiasis (a related fungal infestation), when harmful chemicals create the opportunity. Tracts of tissue in these moist regions, poisoned by heavy antibiotic use, poppers (amyl nitrite) inhalation, cancer chemotherapy, or AZT (about which more below), become the seedbeds for these fungi to thrive, like green mould on damp bread. Doubters might wonder why in South Africa, only the rich who can afford AZT – alone, or as the basis of triple-therapy cocktails – develop PCP. Not penurious blacks, the overwhelming majority of HIV-positives here, both proportionately and in gross numerical terms. Their ‘AIDS indicator diseases’, if they ever develop, are the dull sicknesses that the poor in Africa have always endured. Nothing exotic like PCP.
Not only can AZT “unmask silent opportunistic infections”, it can exacerbate clinically conspicuous ones. Havlir and Barnes reported in February in the New England Journal of Medicine that HIV-positive Tuberculosis patients treated with (AZT-based) ‘antiretroviral therapy’ developed “paradoxical worsening of disease…in up to 36 percent of (them), characterized by fever, worsening chest infiltrates on radiograph, and peripheral and mediastinal lymphadenopathy…(whereas) only 7 percent of patients who received antituberculosis therapy but not antiretroviral therapy had paradoxical reactions.”
In the Esquire article, Saag complains that the death rate of his patients on combinations of AZT, its chemical cousins like 3TC and ddI, and protease inhibitors is on the rise: “They aren’t dying of a traditionally defined AIDS illness,” he says. “I don’t know what they’re dying of, but they are dying. They’re just wasting and dying.” Could it be that cell-poisons poison cells? But such myopia is par for AIDS doctors who learn their trade by rote. And from drug advertisements. Of course the thought that Saag is killing his patients with his sponsors’ drugs is probably too awful to entertain. “It is sobering;” Saag continues, “while we are making good guesses, they are just guesses. We don’t know what we are doing.” It’s hard to disagree. How good the treatment guesses are was revealed during an interview by Ted Koppel on Nightline on 19 May. Saag admitted that “unfortunately, right now, the roller coaster is headed back downhill. And it’s not really clear how far down it’s going to go, but the momentum right now is certainly in the wrong direction.”
US AIDS treatment specialist Dr Joseph Jemsek is more forthright. On 8 January, he was interviewed on the ABC television news show 20/20:
Q: And…in addition, the drugs themselves could kill her by damaging her heart, liver, her pancreas.
JJ: The drugs aren’t perfect. They cause side effects, which are cumulative and inexorable. Now I’m starting to see people die again.
Q: So people are actually dying of the side effects of these…
JJ: Yes, you’re…
Q: …anti-viral drugs?
JJ: Yes, you’re starting to see that.
Martin’s happy claim that AZT cocktails afford “long-lasting beneficial effects” was refuted in November 1997, when Lemp et al reported in the Journal of Acquired Immune Deficiency Syndrome and Human Retrovirology that with HAART, “the treatment benefit is temporary and confers no long-term survival advantages.” Obviously. How could it possibly? Would you nurse your wilting pot-plant with weed-killer? In the clever age, whatever happened to common sense? At last some lay folk are waking up; Steven Gendin wrote an article in the January issue of AIDS-drugs-promoting rag POZ, candidly entitled, “If the virus doesn’t get you, the drugs you take will.” He’s seen enough of his friends fade away on AZT to know.
That AZT, the mainstay of HAART, is entirely ineffective as a therapy was borne out clearly by the large-scale Concorde trials in Europe, reported in The Lancet in April 1994. Embarrassingly for Glaxo-Wellcome, and disastrously for its share prices, the fabulous results of the chaotic American study that had preceded FDA approval of AZT couldn’t be reproduced. Glaxo-Wellcome’s representatives on the trial’s coordinating committee refused to sign the report. Understandably – they could hardly endorse a finding that their flagship money-spinner didn’t live up to its billing. (Its demonstrated therapeutic irrelevance led to AZT’s employment as a drug combined with others – all equally ineffective on their own, as if to mix three toxic duds would be to conjure them miraculously into a medicinal marvel.) In fact not only was AZT found to be useless at the end of the Concorde trials, it was found to be positively harmful: Phillips et al reported in a letter to the New England Journal of Medicine in March 1997 that, “Extended follow-up of patients in one (AZT) trial, the Concorde study, has shown a significantly increased risk of death among the patients treated early.” (Another important finding by the trial’s overseers was that CD4 cell counting was a waste of time, and bore no relation to clinical health. Emphasizing the worthlessness of the practice in Annals of Internal Medicine in 1996, Fleming and DeMets described it as being “as uninformative (an indication of immune status) as a toss of a coin.” Not that anyone took any notice. Today, patients terrified by their doctors’ mournful announcements of their low cell counts – still taken as a signal of collapsing health and imminent demise – are inspired to start with ‘antiretrovirals’, following which the prophesy will be faithfully fulfilled.)
Martin’s silly statement that AZT and 3TC “improves quality of life” is just stale advertising propaganda quoted mindlessly from some glossy ad. The trouble that doctors have with patient ‘non-compliance’ is notorious, due to the intolerable, excruciating ‘side-effects’ of these drugs. Numerous papers have detailed these problems, most recently for example, Nicholson: Managing side-effects: practical advice on dealing with side-effects of antiretroviral therapies in AIDS Treatment Update, October 1998. In 1994, Lenderking et al of the Harvard School of Public Health, reporting their Evaluation of the Quality of Life Associated With Zidovudine Treatment in Asymptomatic Human Immunodeficiency Virus Infection in the New England Journal of Medicine, found “a reduction in the quality of life due to severe side effects of therapy” and the “severe adverse events” it caused, which were “life-threatening in some cases.” Martin’s claim to “quality of life” on AZT sounds reminiscent of the promise of Arbeit Macht Frei.
Here are some of AZT’s ‘side-effects’ listed by its manufacturer: Body as a Whole: abdominal pain, back pain, body odor, chest pain, chills, edema of the lip, fever, flu syndrome, hyperalgesia; Cardiovascular: syncope, vasodilation; Gastrointestinal: bleeding gums, constipation, diarrhea, dysphagia, edema of the tongue, eructation, flatulence, mouth ulcer, rectal hemorrhage; Haemic and Lymphatic: lymphadenopathy; Musculoskeletal: arthralgia, muscle spasm, tremor, twitch; Nervous: anxiety, confusion, depression, dizziness, emotional lability, loss of mental acuity, nervousness, paresthesia, somnolence, vertigo; Respiratory: cough, dyspnea, epistaxis, hoarseness, pharyngitis, rhinitis, sinusitis; Skin: acne, changes in skin and nail pigmentation, pruritus, rash, sweat, urticaria; Special senses: amblyopia, hearing loss, photophobia, taste perversion; Urogenital: dysuria, polyuria, urinary frequency, urinary hesitancy.
In truth, AZT makes you feel like you’re dying. That’s because on AZT you are. How can a deadly cell-toxin conceivably make you feel better as it finishes you, by stopping your cells from dividing, by ending the vital process that distinguishes living things from dead things? Not for nothing does AZT come with a skull and cross-bones label when packaged for laboratory use. Here’s a typical experience of AZT; last year in September, several newspapers in the US and Canada ran a story KIDS WITH AIDS by Gayle Melvin: “Robert Swanson’s medicines came with horrible side-effects: nausea, diarrhea and blinding headaches… Robert would secretly skip a dose of medicine. ‘I’d find his pills all over the place, in his room, in the dirty clothes’, Britten says… ‘When you think of medicine, you think of something that makes you better, but I don’t feel better when I take it,’ Robert says. ‘I’d rather feel good and let the virus take over than feel bad and take the medicine.’ …Tina (takes) AZT,…ddC and Viracept, a protease inhibitor…three times a day. Then she waits to get sick. ‘My head will start to hurt all over, like a pounding. I get dizzy. Sometimes I throw up,’ she says in her sweet, girlish voice. She gets sick every time? ‘Every time’, says Tina… As they go through their teens, these children face (the) challenges (of) taking responsibility for their…often debilitating medical regimen.”
For an early clinical report of AZT poisoning: Dr Laura Bessen and her colleagues wrote a letter to the New England Journal of Medicine in March 1988 headed, Severe Polymyositis-like Syndrome Associated With Zidovudine Therapy of AIDS and ARC. They reported, “All patients had an insidious onset of myalgias, muscle tenderness, weakness, and severe muscle atrophy favouring the proximal muscle groups. Physical examinations revealed varying degrees of muscle weakness and grossly apparent atrophy. Weight loss due to muscle loss was uniformly noted; in one patient, the loss was a striking 18kg.” (A colleague of mine treated with AZT went this way. After just two months of AZT treatment, he lost most of his muscle mass, and died weighing 40kg.) Besson et al noted, “We did not observe this illness before zidovudine was available…” It sure wasn’t the HIV, because the doctors found that “the syndrome was ameliorated after the drug was stopped.”
Besson and her colleagues’ clinical observations were investigated and reported by Dalakas et al in 1990 in the New England Journal of Medicine. Comparing the myopathy (muscle wasting) caused by AZT with that presumed to be caused by HIV, they concluded that “long-term therapy with zidovudine can cause a toxic mitochondrial myopathy, which…is indistinguishable from the myopathy associated with primary HIV infection… Before 1986, when zidovudine (formerly called azidothymidine) was introduced, the number of patients with HIV-associated myopathy was small, and myopathy was considered a rare complication of HIV infection. During the past two years, an increasing number of patients receiving long-term zidovudine therapy have had myopathic symptoms such as myalgia (in up to 8 percent of patients), elevated serum creatine kinase levels (in up to 15 percent), and muscle weakness. These symptoms generally improve when zidovudine is discontinued.” Whether muscle wasting ever occurs among HIV-positives who avoid AZT and related drugs is doubtful: Coker et al reported in AIDS in 1991, “A clinically significant myopathy that precedes the development of zidovudine associated mitochondrial myopathy has been a rarity in our experience.”
In 1991, in Neuromuscular Disorders, Chariot and Gherardi reported, “Long term therapy with (AZT) can induce a toxic myopathy associated with mitochondrial changes.” Looking into biochemical mechanisms to account for the toxicity of AZT for mitochondrial DNA, Hayakawa et al reported their study of mice given AZT, in the journal Biochemical and Biophysical Research Communications in 1991. They proposed “oxygen damage of mitochondrial DNA (to be) the primary cause of mitochondrial myopathy with AZT therapy (and emphasized that) it is urgently necessary to develop a remedy substituting this toxic substance, AZT.” The burden of these reports is plain: AZT rots your muscles. As it does so, the patient enjoys Martin’s “quality of life” as he inexorably slips away with the wasted appearance of an extermination-camp victim. AIDS then goes onto the death certificate, and the image of the white AIDS patient who horribly and mysteriously wastes away is reinforced in the popular consciousness, another AIDS case to chalk up to the statistical tally. (No one cared much about wasting in Africa, commonplace from time immemorial where poverty-linked tuberculosis, malaria and gut diseases are endemic, until its opportunities for research grants popped up when it was renamed ‘slim disease’ or AIDS.)
In his reply to my essay, Martin admits that AZT destroys bone marrow, but then hedges: HIV “may” be the real culprit. This is a tired old tale rehashed. Mercury and arsenic salts – doctors’ favourites for ages – poisoned the patient, whose death was then blamed on unbalanced humours or germs. That AZT destroys bone marrow is frankly declared by its manufacturer. So let’s not fudge. In 1987 Parkash reported in Annals of Internal Medicine, “Four patients with the acquired immunodeficiency syndrome, and a history of Pneumocystis carinii pneumonia developed severe pancytopenia 12 to 17 weeks after the initiation of azidothymidine therapy. Partial bone marrow recovery was documented within 4 to 5 weeks (after discontinuation of AZT) in three patients, but no marrow recovery has yet occurred in one patient during the more than 6 months since AZT treatment was discontinued.” For AIDS doctors slow to the point, Dainiak et al spell it out in their 1988 paper in the British Journal of Haematology, entitled, 3’-Azido-3’-deoxythymidine inhibits proliferation in vitro of human haematopoietic progenitor cells. They reported, “Anaemia (during AZT therapy) appears to be due to bone marrow suppression.” Consistent with this, Costello reported in the same year, in the Journal of Clinical Pathology that, “Blood transfusion is often necessary in patients with AIDS, especially in those receiving AZT, a drug which produces severe anaemia in a proportion of recipients. Forty nine (36%) of 138 patients treated with AZT required blood transfusion at least once.” Harrison’s Principles of Internal Medicine confirms: “(AZT), used for treating (HIV), often causes severe megaloblastic anemia…caused by impaired DNA synthesis.”
AZT reaches and can destroy foetal bone marrow too. In the May 1998 issue of the Pediatric Infectious Diseases Journal, Watson et al at the University of Rochester Medical Center in New York reported the grim case of an HIV-negative baby born to a positive mother who had been treated with a HAART cocktail of AZT, 3TC and a protease inhibitor, suffering “high output congestive heart failure secondary to profound anemia.” The paediatricians excluded “infection, nutritional deficiencies, congenital leukemia and congenital red blood cell aplasia in the child” and considered the “cause of the life-threatening anemia in our infant…to be in utero erythroid marrow suppression by one or more of the antiretroviral agents administered to the mother.”
Martin alleges that “toxicity in most cases is reversible.” This optimistic jive is flatly contradicted by Mir and Costello, who reported their concern in The Lancet in 1988 that “bone marrow changes in patients on zidovudine seem not to be readily reversed when the drug is withdrawn. These findings have serious implications for the use of zidovudine in HIV positive but symptom-free individuals.”
As for the fabled power Martin claims for AZT to prevent pregnant women transmitting HIV to their foetuses, Bennet observed in AIDS/STD Health Promotion Exchange 1998 that, “At present, data regarding the effects of ZDV (AZT) use on vertical transmission rates are inconclusive and incomplete. In addition, the long-term effects of ZDV use during pregnancy and after birth on the woman and any resulting child are yet to be discovered. The possibility has not yet been ruled out that this ‘risk-reducing’ measure may not be effective and may prove detrimental to the health of both mother and child.”
Bennet’s caveat has moved from the hypothetical to the tragically real. In February, French researcher Stephane Blanche announced at the Sixth Conference on Retroviruses and Opportunistic Infections that two babies in an AZT trial that he and colleagues were conducting had apparently been killed by the drug. Both had fallen sick at four months and had died of mitochondrial dysfunction and neurological defects – conditions ordinarily very rare. In September, in his paper in The Lancet entitled Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues, he reported: “We analysed observations of a trial of tolerance of combined zidovudine and lamivudine and preliminary results of a continuing retrospective analysis of clinical and biological symptoms of mitochondrial dysfunction in children born to HIV-1-infected women in France…. Eight children had mitochondrial dysfunction. Five, of whom two died, presented with delayed neurological symptoms and three were symptom-free but had severe biological or neurological abnormalities. Four of these children had been exposed to combined zidovudine and lamivudine, and four to zidovudine alone. No child was infected with HIV-1… Our findings support the hypothesis of a link between mitochondrial dysfunction and the perinatal administration of prophylactic nucleoside analogues.….. Further assessment of the toxic effects of these drugs is required.” On the same theme, in the same issue of The Lancet, Dutch researchers Brinkman et al published a paper recording their view that AZT class drugs “are much more toxic than we considered previously.” Discussing the body-wasting characteristic of AZT-treated patients, they point out that, “The layer of fat-storing cells directly beneath the skin, which wastes away…is loaded with mitochondria… (O)ther common side effects of (AZT and like drugs are) nerve and muscle damage, pancreatitis and decreased production of blood cells… all resemble conditions caused by inherited mitochondrial diseases.”
American researchers (Culnane et al), who in January had claimed in the Journal of the American Medical Association that AZT appeared to be safe for babies, were incredulous when Blanche made his conference announcement. Which is odd, because a month earlier a paper in AIDS by Lorenzi et al at Hopital Cantonal Universitaire in Geneva reported that, “Following combination antiretroviral therapy administered during pregnancy, most HIV-positive mothers and about half of their children developed one or more adverse events.” Of thirty babies, “the most common adverse event was prematurity (ten infants), followed by anaemia (eight). The investigators also noted two cases of cutaneous angioma, two cases of cryptorchidism, and one case of transient hepatitis. Two infants…developed… intracerebral hemorrhage…(and one,)…extrahepatic biliary atresia.”
None of this is really surprising since as early as 1990, Gillet et al had reported in the Journal of Gynecology, Obstetrics, and Biological Reproduction that “concentrations of (AZT) in the liquor and in the fetal blood (of six aborted human foetuses) were higher or equaled those found in the maternal blood.” They reiterated accordingly, “The drug remains contra-indicated in pregnancy.” Not least because the FDA categorises AZT as a ‘C’-class drug for safety in pregnancy. With such drugs, it warns, “Safety in human pregnancy has not been determined, animal studies are either positive for fetal risk or have not been conducted, and the drug should not be used unless the potential benefit outweighs the potential risk to the fetus.”
In a paper published in Mutation Research in 1997, Argawal and Olivero reported, “AZT induces significant toxic effects in humans exposed to therapeutic doses… Cytogenetic observations on H9-AZT cells showed an increase in chromosomal aberrations and nuclear fragmentation when compared with unexposed H9 cells (and) the mechanisms of AZT induced cytotoxicity in bone marrow of the patients chronically exposed to the drug in vivo may involve both chromosomal and mitochondrial DNA damage.” This might explain Kumar et al’s 1994 report in the Journal of Acquired Immune Deficiency Syndrome and Human Retrovirology of a shocking number of therapeutic and spontaneous abortions, and, of the live births, a ten per cent abnormality rate among one hundred and four cases of pregnant women treated with AZT in a hospital in India. The grotesque birth defects included holes in the chest, abnormal indentations at the base of the spine, misplaced ears, mis-shapen faces, heart defects, extra digits and albinism. Doesn’t the doctor’s Hippocratic promise not to administer poison apply anymore?
The danger for developing foetuses posed by the administration of AZT to pregnant mothers was highlighted in 1997 by Ha et al in the Journal of Acquired Immune Deficiency Syndrome and Human Retrovirology in a paper entitled, Fetal, infant, and maternal toxicity of zidovudine (AZT) administered throughout pregnancy in Macaca nemestrina. The researchers reported, “The AZT animals (Macaque monkeys given AZT during pregnancy) developed an asymptomatic macrocytic anemia, but hematologic parameters returned to normal when AZT was discontinued. Total leukocyte count decreased during pregnancy and was further affected by AZT administration. AZT-exposed infants were mildly anemic at birth. AZT caused deficits in growth, rooting and snouting reflexes, and the ability to fixate and follow near stimuli visually.” The latter indications of neurological damage were anticipated in their 1994 paper in the same journal, Fetal toxicity of zidovudine in Macaca nemestrina: preliminary observations. They found that, “AZT-exposed infants took three times as many sessions (6) as controls (2) to meet criterion on Black-White Learning, a simple discrimination task (and were)…significantly (worse in locating) the reward…” That’s not all they found either: “Postnatal weight increase was significantly lower in AZT-exposed infants… Hemoglobin dropped significantly in the AZT-treated animals after treatment began and remained low until the end of the study… Platelet counts increased significantly in AZT-treated animals during the treatment period but returned to control levels before the end of the study… The mechanism for the elevation of platelet count in AZT-treated animals is unknown… The hematological toxicities reported here are consistent with those seen in 500 mg/day AZT-treated humans.” Incredibly, Connor et al in their piece (discussed in my first essay) Reduction of Maternal-Infant Transmission of Human Immunodeficiency Virus Type 1 with Zidovudine Treatment, the pitiful if hugely popular paper in the New England Journal of Medicine in 1994 propounding the administration of AZT to pregnant women, rely on Ha et al‘s just-mentioned 1994 monkey research report for the comforting conclusion, “Based on these findings, we predict that there would be no significant toxic effects of prenatal AZT exposure (100 mg/dose; 500 mg/day) in humans.” In the light of all that was already known about the acute toxicity of AZT, and it would be reinforced by later studies, what better illustration of Erasmus’ foresight in the 16thcentury that the dullest, most ignorant and incautious doctors would become the superstars of the AIDS age, and that for their experiments on pregnant women with cell-poisons they’d be not abjured but celebrated. On trial, no doubt, they would defend their science in radical ideological terms like the doctors at Nuremberg. The evil they perceived called for ruthless measures to root out, and in such struggles conventional civilised restraints on medical experiments on humans fall by the way.
As an advocate of AZT for HIV-positive children, Martin might like to venture an explanation for this: In a study in the US, designed by Dr. Janet Englwood, and sponsored by both the National Institute of Allergies and Infectious Diseases and the National Institute of Child Health and Human Development, eight hundred and thirty nine HIV-positive children were divided into three groups and treated with AZT, ddI and a combination of both respectively. The ‘AZT alone’ wing of the study had to be abruptly called off in February 1995 due to the “more rapid rates of…bleeding and biochemical abnormalities” exhibited by the children in this group. For the answer, here’s a clue. In 1997, Benbrick et al reported a study by researchers at several French institutions in the Journal of Neurological Science; comparing AZT with other similar nucleoside analogue drugs used in AIDS treatment, they found that although “all (such drugs) exert cytotoxic effects on human muscle cells and induce functional alterations of mitochondria…AZT seemed to be the most potent inhibitor of cell proliferation.”
Consonant with this finding, in 1997 in the journal Clinical Infectious Diseases, Heresi et al reported fungal infestations (PCP) which developed in the lungs of two HIV-negative babies, born healthy, whose mothers had been treated with AZT followed by the babies themselves for six weeks. No mystery about it. Under the entry ‘Retrovir’ (AZT’s trade name), The Physician’s Desk Reference hints delicately, “It was often difficult (in AZT clinical trials) to distinguish adverse events possibly associated with administration of Retrovir from underlying signs of HIV disease or intercurrent illnesses.” In similar terms, the 16th edition of the manual USP DI: Drug Information for the Health Care Professional published in 1996 by the United States Pharmacopeial Convention states that “it is often difficult to differentiate between the manifestations of HIV infection (again presumed) and the manifestations of zidovudine. In addition, very little placebo controlled data is available to assess this difference.” To put a point on it, AZT itself can cause AIDS-defining illnesses. Its critics have been saying so for years. What else is one to make of Buchbinder et al’s finding reported in AIDS in 1994 that, “Only 38% of the HLP (healthy long-term (>10 years) positives) had ever used zidovudine or other nucleoside analogues, compared with 94% of the progressors”? Or Washington University’s Assistant Professor of Medicine Dr Carl Fichtenbaum’s observation about Mycobacterium avium complex disease in his article I Hear You Knockin’ in the magazine Research Initiative Treatment Action: “Mycobacterium avium complex disease is one of the most common OI’s in persons with advanced HIV disease. It has been observed in 15 to 40% of persons with HIV infection. The incidence of MAC began with AIDS reported to the CDC had MAC disease. Of note, the incidence increased from 5.7% in 1985-86 to 23.3% in 1989-90. Thus, MAC disease has become one of the most frequent OI events occurring in individuals with CD4+ lymphocyte counts <50 cells/mm3.” Funny how the disease incidence suddenly ballooned coincidentally with the introduction of AZT as an AIDS drug in 1986-7.
In the June issue of the New England Journal of Medicine, Learmont et al report the interesting case of eight “transfusion recipients…infected with…HIV-1…from a single donor before 1985… Since then, two subjects died of causes unrelated to HIV-1 infection. The (cause of) death of one other subject, in 1987 (is indeterminate, and the five other) recipients are still asymptomatic 14 to 18 years after infection and have not received antiretroviral therapy.” Wonder of wonders. Likewise, in the July issue of the Journal of Medical Virology, Candotti et al‘s study of sixty eight ‘long term non-progressors mentions coincidentally that none were on “antiretroviral therapy”. This tallies with the observation of prominent AIDS researcher Dr Jay Levy, Professor of Medicine at the University of California at San Francisco, in The Lancet last year that “long-term survivors of HIV” have all avoided ‘antiretrovirals’. Similarly Dr Donald Abrams, Professor of Medicine and Director of the AIDS program at San Francisco General Hospital, noted in 1996: “I have a large population of people who have chosen not to take any antiretrovirals… I’ve been following them since the very beginning… They’ve watched all of their friends go on the antiviral bandwagon and die.”
In 1997, The Canadian Pharmaceutical Association noted, “The long-term consequences of in-utero and infant exposure to zidovudine are unknown. The long-term effects of early or short-term use of zidovudine in pregnant women are also unknown.” Likewise the US Centers for Disease Control’s April 1998 Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection cautioned, “Data from clinical trials that address the effectiveness of antiretroviral therapy in asymptomatic infants and children with normal immune function are not available… The theoretical problems with early therapy include the potential for short- and long-term adverse effects, particularly for drugs being administered to infants aged <6 months, for whom information on pharmacokinetics, drug dosing, and safety is limited…(and) clinical trial data documenting therapeutic benefit from (antiretroviral therapy) are not available.”
However, in his paper in AIDS in May, Rapid disease progression in HIV-1 perinatally infected children born to mothers receiving zidovudine monotherapy during pregnancy, Professor de Martino, Coordinator of the Italian Register of HIV Infected Children at the Department of Paediatrics, University of Florence in Italy reports that, “Comparison of HIV-1-infected children whose mothers were treated with ZDV with children whose mothers were not treated showed that the former (AZT treated) group had a higher probability of developing severe disease [57.3%…versus 37.2%]…or severe immune suppression [53.9%…versus 37.5%…] and a lower survival (rate) [72.2%…versus 81.0%…].” How does this square up with Martin’s urging that AZT be given to pregnant women for the benefit of their children? In similar vein, in her jolly piece in the San Francisco Examiner on 31 May, Thailand wins a round against HIV, Karen Emmons reports, “Of the children who were born HIV-positive in Bangkok in the past four years and received the combination drug treatment (AZT and ddI)…one-fourth died in their first year, about 33 percent by their second year, 40 percent by age 3, and then the mortality tapered off.” This is a medical victory? On these data, a critical journalist might have reported an iatrogenic drug disaster.
That’s just what some observers think AIDS in the US largely to have been, and if one looks at the CDC’s AIDS mortality figures read against the frequency of AZT use there, it’s not hard to see why. AIDS deaths trebled between 1988 and 1989 with the recommendation that AZT be given to asymptomatic HIV-positives; they rose steadily by 1994/5 to fifteen times what they had been prior to the introduction of AZT as an AIDS drug in 1986/7, and then fell precipitously – by 1997 to less than half of the 1994/5 death rate following the abandonment of AZT-monotherapy in favour of ‘combination therapy’, still toxic but not as immediately so. The peculiar part of it is that having been found to be too poisonous and ineffective as a monotherapy for adults by 1994, AZT should thereafter be commended for babies in utero.
One would think that all this would give pause to doctors plying this drug on pregnant women, but not in the debased scientific atmosphere of the AIDS era. One wonders whether the First Precept of the Nuremberg Code – informed consent – formulated after the Nazi medical experience, is ever observed with such dangerous experimental treatment. Any bets on whether these women are told, for instance, of Olivero et al’s report in 1997 in the Journal of Acquired Immune Deficiency Syndrome and Human Retrovirology bluntly headed, AZT is a Genotoxic Transplacental Carcinogen in Animal Models? The researchers reported that, “In newborn monkeys and mice, AZT was incorporated into DNA of many fetal tissues… AZT appears to be a moderately-strong transplacental carcinogen… (and in) adult mice, lifetime AZT administration induces vaginal tumors at a 10-20% incidence.” Or of the same researchers’ other paper in 1997 in the Journal of the National Cancer Institute entitledTransplacental effects of 3’-azido-2’,3’-dideoxythymidine: tumorigenicity in mice and genotoxicity in mice and monkeys? In the light of earlier rodent studies which found AZT “to be carcinogenic in adult mice after lifetime oral administration”, the research team, all scientists with the US National Cancer Institute, were concerned to assess “the transplacental tumorigenic and genotoxic effects of AZT in the offspring of…mice and…monkeys given AZT orally during pregnancy.” Pregnant mice and monkeys were given AZT in the second halves of their gestational terms. After exposure to AZT in the womb, the offspring of these animals were not further treated. By one year of age, the mice exposed to AZT in utero “exhibited statistically significant, dose-dependent increases in tumor incidence and tumor multiplicity in the lungs, liver, and female reproductive organs. AZT incorporation into nuclear and mitochondrial DNA was detected in multiple organs of transplacentally exposed mice and monkeys. Shorter chromosomal telomeres were detected in liver and brain tissues from most AZT-exposed newborn mice but not in tissues from fetal monkeys.” The researchers concluded, “AZT is genotoxic in fetal mice and monkeys and is a moderately strong transplacental carcinogen in mice examined at 1 year of age. Careful long-term follow-up of AZT-exposed children would seem to be appropriate.” Since, “AZT is unequivocally a transplacental genotoxin and carcinogen (and) given transplacentally to mice, benzopyrene produced lung and liver tumour multiplicities similar to those observed (with AZT)”, the researchers recorded their concern that “the current practice of treating HIV-positive women and their infants with high doses of AZT could increase cancer risk in the drug-exposed children when they reach young adulthood or middle age.”
Nor does it seem very likely that HIV-positive pregnant women will be told of Olivero et al’s paper in AIDS in May, reporting the research of a major collaborative investigation by several institutions in the US, overseen by The National Cancer Institute: In view of the just-mentioned 1997 animal research findings, the researchers were concerned to establish whether their observations applied to humans, that is, whether AZT administered to HIV positive pregnant women was incorporated into their DNA and that of their babies. It was found that it was. The ramifications of this for the potential human carcinogenicity of AZT were conveyed in the researchers’ recommendation that “the biologic significance of ZDV-DNA damage and potential subsequent events, such as mutagenicity, should be further investigated in large cohorts of HIV-positive individuals (because)…these data raise the possibility that the presence of extensive ZDV incorporation into human DNA may be cumulative, with potential long-term consequences such as mutagenicity and tumorigenicity.”
And it sure would be surprising were these women – advised to go on a bracing ‘short course’ of AZT treatment – to be told about Olivero’s paper in Mutation Research in July: 3’-azido-3’-deoxythymidine transplacental perfusion kinetics and DNA incorporation in normal human placentas in similar terms perfused with AZT: Olivero and Poirier of the Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, USA, and Parikka and Vahakangas of the Department of Pharmacology and Toxicology, University of Oulu, Finland. Concerned because “transplacental exposure studies demonstrated that AZT is a moderate to strong transplacental carcinogen in mice (and) the consequences of transplacental AZT exposure to the fetus remain unknown”, the researchers investigated “the extent and kinetics of AZT transfer across the human placenta.” They reported, “Since AZT crosses the human placenta and becomes rapidly incorporated (within 2 hours of AZT perfusion) into DNA of placental tissue in a dose-dependent fashion, (this suggests) that even short exposures to this drug might induce fetal genotoxicity… In previous studies AZT has been shown to produce both large-scale DNA damage and point mutations. Skin tumors induced in mice by transplacental AZT initiation and subsequent topical promotion had mutations in Ha-ras Exon I codons 12 and 13, but these mutations were not observed in liver and lung tumors from mice given the same exposure. The fact that the recommended treatment involves AZT use for the last 6 months of pregnancy, suggest that human fetuses may also sustain AZT-DNA damage… (T)he consequences of any fetal exposure to a nucleoside analog, in utero, remain unknown and a long-term follow up of children prenatally exposed seems to be appropriate.”
Reporting to the US Surgeon General in 1970, the Ad Hoc Committee on the Evaluation of Low Levels of Environmental Chemical Carcinogens recommended, “Any substance which is shown conclusively to cause tumors in animals should be considered carcinogenic and therefore a potential cancer hazard for man… No level of exposure to a chemical carcinogen should be considered toxicologically insignificant for man. For carcinogenic agents a ‘safe level for man’ cannot be established by application of our present knowledge…” Have the rules changed? Is AZT too big to ban (under the Delaney Amendment outlawing potentially carcinogenic drugs in the US)? Or are the rules about exposing patients to likely carcinogens just relaxed a bit when they are female and pregnant? Or black or gay?
In fact the likely carcinogenicity of AZT, demonstrated by these recent studies, is no news at all. Way back in December 1986, a review of numerous AZT studies entitled Review & Evaluation of Pharmacology & Toxicology Data was submitted to the US Food and Drug Administration by its in-house toxicology analyst Dr Harvey Chernov. He reported – apart from the observation that AZT was toxic to bone marrow and caused anaemia in all species (of experimental animal) including man – that AZT “was found weakly mutagenic in vitro in the mouse lymphoma cell system. Dose-related chromosome damage was observed in an in vitro cytogenetic assay using human lymphocytes”, and AZT was found to be active in the Cell Transformation Assay, a stock test for carcinogenic potential. He emphasized, “This BALB/c-3T3 neoplastic transformation assay was performed according to standard operating procedure. Concentrations of AZT as low as 0.1 mcg/ml reduced the number of cells in culture after a 3-day exposure. A statistically significant increase in the number of aberrant ‘foci’ was noted at concentration of 0.5 mcg/ml. This behaviour is characteristic of tumor cells and suggests that AZT may be a potential carcinogen. It appears to be at least as active as the positive control material, methylcholanthrene.” As Chernov explains it, “A test chemical which induces a positive response in the Cell Transformation Assay is presumed to be a potential carcinogen.” Naturally he advised the FDA against approving AZT, but his report was buried. Indeed, it had to be flushed out of the FDA’s files by resort to the machinery of the federal Freedom of Information Act, some years later.
Chernov’s bleak predictions have since been realised. But you’d never know it reading the tortured spin of AZT promoters Broder et al in their piece, Clinical Pharmacology of 3′-Dideoxythymidine and Related Dideoxynucleosides, published in the New England Journal of Medicine in 1989. Conceding that “it is of particular concern that the drug may be carcinogenic or mutagenic” and “its long term effects are unknown”, the authors state, “zidovudine may be associated with a higher incidence of cancers in patients whose immunosurveillance mechanisms are disturbed simply because it increases their longevity.” Just muse on that as a vignette illustrating the quality of reasoning exhibited by AIDS scientists, and then before you dry your eyes, dig this – from the same illustrious peer-reviewed journal: In 1988, Pizzo et al claimed that AZT boosted the IQ points of twenty one HIV-positive children by fifteen points. In declaiming these AZT-boosted “neurodevelopmental” improvements, the excited researchers relegated the deaths of five of the children on AZT to a passing mention. But not even that for the dead children when Glaxo-Wellcome seized on and punted this garbage as a selling hook when advertising AZT in The Lancet.
Actually, AZT doesn’t make you clever, it makes you stupid. You may have heard of ‘AIDS-dementia’. It’s like ‘neuro-syphilis’ – which no one gets anymore, now that penicillin has taken over from arsenic and mercury salts to kill syphilis spirochaetes. To be told by a doctor that you’re about to die would knock the best of us off the psychological rails. Certainly I’ve seen this in two AIDS-based cases I’m conducting. (At the least of it, the diagnosis per se can precipitate a health collapse, as a glance at Ader, Felten and Cohen’s text, Psychoneuroimmunology will confirm.) Bacellar et al reported in the journal Neurology in 1994 that “the risk of developing HIV dementia among those reporting any antiretroviral use (AZT, ddI, ddC, or d4T) was 97% higher than among those not using this antiretroviral therapy… In addition, the findings of our analysis seem to confirm previous observation of a neurotoxic effect of antiretroviral agents…linked…to the development of toxic sensory neuropathies, usually in a dose-response fashion.” Remember the sensory and mental disturbances mentioned above on the package blurb as being among AZT’s ‘side-effects’? You know, the ones caused by the poisoning of your nerves and brain? Heald et al mentioned some of them in their paper in AIDS in 1998, Taste and smell complaints in HIV-infected patients. In a discussion of mitochondrial myopathy, Robbin’s Pathologic Basis of Disease mentions mitochondrial encephalomyopathy. The Concise Oxford Medical Dictionary tells us that encephalomyopathy is “extensive destruction of nerve cells throughout the nervous system (causing) widespread disease of brain and spinal cord.”
In the May issue of Clinical Infectious Diseases, Fichtenbaum et al at the Washington University School of Medicine describe the cases of three patients who developed progressive multifocal leukoencephalopathy after four to eleven months of HAART. Despite a change in their treatment, the research team “observed no improvement (in two of the cases)… Neurologic deterioration continued, and (the) patients died within 2 months.” They concluded that the condition can “develop while using HAART” notwithstanding test results suggesting “a good virologic response to antiretroviral therapy.” That the drugs themselves caused the brain and neurological damage, they didn’t consider. Apparently Fichtenbaum and his portly pals found the logical leap too wide to hazard. But not Research Initiative Treatment Action in their piece headed Just Sweat it Out: Physical therapy’s role in the HIV pandemic under the chapter, The Nervous System and Physical Therapy: “Peripheral neuropathy pain, which occurs in 40 to 60% of people with AIDS, is one of the most common causes for referral to physical therapy and is often one of the most neglected. Symptoms of peripheral neuropathy include burning, numbness, and/or a tingling sensation of the extremities. Lower extremity involvement is more common than upper extremity involvement. Problems with ambulation, balance, and compensatory low back pain are also commonly associated with peripheral neuropathy.” Since there isn’t a jot of evidence that HIV attacks nerve cells, but ample evidence that nucleoside analogues like AZT, 3TC, d4T, ddI and ddC do, the article concedes that “peripheral neuropathy may be directly related to (such) pharmacological agents…”
If it’s not good for your head, AZT’s not great for your heart either. Lipshultz pointed out in the New England Journal of Medicine in 1998 that “possible mechanisms (for heart muscle disease among HIV-positive patients) include cardiotoxicity as a result of antiretroviral therapy…” And in their paper in Nature Medicine in 1995, Mitochondrial toxicity of antiviral drugs, Lewis and Dalakas mention heart disease among the many manifestations of drug toxicity caused by ‘antiviral’ nucleoside analogues (ANAs) like AZT: “(T)he prevalent and at times serious ANA mitochondrial toxic side-effects are particularly broad ranging with respect to their tissue target and mechanisms of toxicity: Haematalogical; Myopathy; Cardiotoxicity; Hepatic toxicity; Peripheral neuropathy.”
It would appear that AZT and chemically related drugs can blind you too. In the Journal of Infectious Diseases in March, Karavellas and Plumm reported their investigation of “the likelihood of the development of a new ocular inflammatory syndrome (immune recovery vitritis, IRV), which causes vision loss in AIDS patients with cytomegalovirus (CMV) retinitis, who respond to HAART. We followed 30 HAART-responders with CD4 cell counts of >/=3D60 cells/mm3. Patients were diagnosed with IRV if they developed symptomatic vitritis of >/=3D1+ severity associated with inactive CMV retinitis. Symptomatic IRV developed in 19 (63%) of 30 patients…over a median follow-up from HAART response of 13.5 months… These data suggest that IRV develops in a significant number of HAART-responders with CMV retinitis…” It’s amazing. Some ‘successfully’ treated AIDS patients go blind. A brand-new disease construct comes into being: ‘Immune Recovery Vitritis’. Roche hawks its ‘anti-CMV medication’, with advertising directed specifically at gay men whose sight has been wrecked by drug damage to their ocular nerves. In an echo of the Japanese Clioquinol disaster, cytomegalovirus is blamed for the blindness, not the HAART drugs, notwithstanding their well-established neuro-toxicity.
During a polio-like epidemic in the sixties and early seventies in Japan, Subacute Myelo-Optico-Neuropathy or S.M.O.N. caused blindness, paralysis and death in thousands of cases. The Japanese medical research establishment approached the crisis on the footing that some new unknown infectious agent was responsible. Echo-, Coxsackie- and lenti-viruses were put in the dock in turn. Professor Shigeyuki Inoue at Kyoto University’s Institute for Virus Research claimed that a virus he had identified (coincidentally in the same herpes-class as the common-place and generally harmless cytomegalovirus) was the cause of S.M.O.N., and it was accepted as such in the 1974 edition of the American textbook, Review of Medical Microbiology. With modern medicine’s bias to germs as the causes of disease, entirely overlooked was the possibility that the epidemic was caused not by a contagion but by a toxin – until the epidemiological anomalies became uncontainable for the viral culprit theory. Finally, an anti-diarrhoereal drug Clioquinol was found to be the cause. Inadequately tested, it turned out to be neuro-toxic. When it was banned, the plague ceased, and in the litigation that followed its manufacturer Ceiba-Geigy was taken to the cleaners.
But back to cancer. Pluda and colleagues, all researchers with the US National Cancer Institute, no less, reported in 1990 in Annals of Internal Medicine that on AZT, your chances of developing lymphoma relative to the rest of the population went up 50 fold: “The estimated probability of developing (Non-Hodgkin) lymphoma (in patients taking AZT alone, or in combination) by 30 months of therapy was 28.6% and by 36 months, 46.4%.” The authors considered “a direct role of therapy itself” for the development of the disease, and warned, “Zidovudine can act as a mutagen.”
In the light of these reports, is it truthful for AZT manufacturer Glaxo-Wellcome to persist with the assertion, as it does in its AZT package insert that, “It is not known how predictive the results of rodent carcinogenicity studies may be for humans”? After all, “At doses that produced tumors in mice and rats, the estimated drug exposure (for mice) …was (only about) 3 times…the estimated human exposure at the recommended therapeutic dose of 100 mg every 4 hours.” And how frank is Glaxo-Wellcome in disposing of Chernov’s positive Cell Transformation Assay findings with the bald unelaborated statement in the same package insert, “In an in vitro mammalian cell transformation assay, zidovudine was positive at concentrations of 0.5 µg/ml and higher”? How many doctors, let alone patients, appreciate from this that as little as half a millionth of a gram per millilitre of AZT came up positive in a standard drug-industry screening-test for potential drug carcinogenicity? And what risks for patients this portends?
In AIDS in May, Grulich et al report a 16 year study of cancer incidence among people given an AIDS diagnosis in New South Wales, Australia. The researchers noted that among more than 3600 AIDS diagnoses, fully one quarter of the patients had developed cancers including those of lung, skin and lip, leukaemia and Hodgkins Disease – none of which are ‘AIDS indicator diseases’. “There was an increased incidence of several other forms of cancer, some of which are known to occur at increased rates in transplant recipients who have received immunosuppressive therapy.” Presumably these patients had been dosed according to the standard ‘antiretroviral’ treatment protocol – AZT alone or in combination with related drugs. All of which, like ‘immunosuppressive therapy’, are destructive of the cells of the immune system. They report, “The incidence of Hodgkin’s Disease increased significantly at the time of AIDS diagnosis.” Since the disease sets in after the diagnosis is made and the treatment begins, the sensible doctor might wonder about the medicine. Such enquiry might be stimulated by Zietz et al‘s paper in June in the New England Journal of Medicine reporting An unusual cluster of cases of Castleman’s disease during highly active antiretroviral therapy for AIDS. Most patients with this “rare… lymphatic hyperplasia…disease” typically present with “multicentric lymphadenopathy… an interfollicular predominance of plasma cells… and progressive systemic symptoms or with a more localized, indolent disease that can often be cured by local excision.” In the four cases reported, the patients suffered “(f)ever, weakness, generalized enlargement of lymph nodes, and marked polyclonal gammopathy… (and three) died within a week after the diagnosis.” Speculating about the possible causes – the virus HHV-8 is tentatively mooted – the authors note that in all cases “symptoms of multicentric Castleman’s disease started after the initiation of highly active antiretroviral therapy…” Sure they did.
Debunking Martin’s claims as to the efficacy of AZT for “post-exposure prophylaxis” would take more space than the joke warrants. Put it this way. There are no smart-bomb drugs for viruses. Probably never will be. If there were, we wouldn’t have to put up with colds and ‘flu any more. Geddit?! As Nobel Laureate retrovirologist and Director of the US National Institutes of Health, Dr. Harold Varmus summed it up in June last year, “Trying to rid the body of a virus whose genome is incorporated into the host genome may be impossible.” Any honest, competent GP will tell you that viruses are beyond Medicine’s reach. With viral diseases you take it easy and hope for the best. Presuming of course you have the disease you’ve been told you do, but just what HIV antibody test results really tell is another story, and what an unbelievable scientific shambles it is.
Schmitz et al’s paper Side effects of AZT prophylaxis after occupational exposure to HIV-infected blood in Annals of Hematology in 1994 might dampen the ardour of AZT ‘post exposure prophylaxis’ proponents: AZT was supplied to fourteen health care workers “exposed to HIV contaminated blood through needle sticks and similar accidents.” Three abandoned the treatment early because of its unendurable toxicity. Eleven held the course for a month. Four of them developed severe neutropenia. One developed a lung infection. The study itself was called off early before more harm was done. Robbins’ pathology text explains: “The symptoms and signs of neutropenias are those of bacterial infections (and) the most severe forms of neutropenias are produced by drugs.” Hello?
Following the rape recently of prominent South African AIDS journalist Charlene Smith, an intense debate currently rages in the media here about a related issue: whether the State ought to provide AZT and related drugs to rape victims. However the US Centers for Disease Control, the font et origo of most conventional wisdom about AIDS, is not on the side of its protagonists. In CDC Update, dated 29 Sept 1998, it warned, “Potential benefits must be weighed against the risks of drug toxicity (and) the difficulty of compliance with the regimen… Because post-exposure is an experimental therapy of unproven efficacy, it should only be prescribed with the informed consent of the patient, after explanation of the potential benefits and risks. Antiretroviral therapy should never be used routinely…” This advice was based on the conclusions of a conference of experts convened to examine the matter on 24-25 July 1997 in Atlanta. The report of this External Consultants’ Meeting on Antiretroviral Therapy for Potential Nonoccupational Exposures to HIV recorded that “no data currently exist about the effectiveness of such therapy for these types of exposures… There are no human studies of antiretroviral drug therapy for sexual, drug use, or other non-occupational exposures to HIV… Potential benefits have to be weighed against the significant health risks and costs associated with this therapy for nonoccupational exposures. First, these medications can have severe side effects… Second, efficacy is unknown… This therapy should never be routine. It is… complicated…(and) is NOT a ‘morning-after pill’.”
Charlene Smith recently reported Amy Brown’s experience of ‘antiretroviral therapy’ in the Mail and Guardian (15 October). Five months after being raped she came up positive to an HIV antibody test. “I was eleven weeks pregnant and the doctor said Retrovir (AZT) and 3TC are not approved for pregnancy but you have to take it. I lost the baby a week later.” Any wonder?
Finally, for AZT, a ringing epitaph. In June, in a special supplement to the journal Current Medical Research and Opinion, Papadopulos-Eleopulos et al publish an extensive critical analysis of the pharmacology of AZT*. It’s a monumental document (30 000 words) and it explodes all pretensions that AZT has ever had to having any therapeutic value. Reviewing all the principal medical literature on AZT, both early and current, the authors demonstrate that there is “no…evidence” to support early claims that AZT disrupts the “HIV replication cycle by a selective inhibition of viral reverse transcriptase thereby preventing the formation of new pro-viral DNA in permissive, uninfected cells”, that AZT is not triphosphorylated to any significant extent in vivo when administered to patients – a process all HIV experts agree is essential to prevent the formation of pro-viral HIV DNA – and that AZT is incapable of exerting an anti-HIV effect accordingly. On the other hand, the paper mentions “a number of bio-chemical mechanisms (elucidated in the scientific literature) which predicate the likelihood of widespread, serious toxicity for the use of this drug.” The authors wonder, “Based on all these data it is difficult if not impossible to explain why AZT was introduced and still remains the most widely recommended and used anti-HIV drug.” They conclude that the continued administration of AZT “either alone or in combination…to HIV sero-positive or AIDS patients warrants urgent revision.” This indictment of AZT ought to be its death knell in clinical practice. No doctor whose adult or infant patient sickens or dies on AZT will be safe from damages actions founded on medical negligence after this.
It took four centuries before Medicine finally recognised that Calomel (mercurous chloride) couldn’t cure, only kill, and dumped it from its pharmacopoeia. Until then, notwithstanding its manifest poisonousness, doctors had advocated it, some with poetic fervour, as a panacea for gout, headache, menstrual pain, syphilis, and no end of other ailments. No modern doctor, especially any who has seen that ghastly clip of Japanese families crippled by mercury poisoning in Minamata Bay in the fifties, or our own recent victims – former workers at the Thor mercury-waste ‘reprocessing’ plant in KwaZulu-Natal – would dream of ladling mercury salts down their patients’ throats nowadays. When is the penny going to drop with AZT?
The repackaging of lethal cell-poisons like AZT as ‘anti-retrovirals’ is a vast and vicious pharmaceutical fraud. But as a Greek Cynic noted appositely a couple of millennia ago, the law has always been a web in which small flies get caught; the great ones burst through.
So much for Doc Martin’s Celestial Elixir.
Thanks and credit to David Crowe, Peter Duesberg, Bryan Ellison, Celia Farber, Charles Geshekter, Billi Goldberg, Mathew Irwin, James Jerome, John Lauritsen, Todd Miller, Eleni Papadopulos-Eleopulos and Val Turner.
by Anthony Brink
When a doctor does go wrong he is the first of criminals. He has nerve and he has knowledge.
Sir Arthur Conan Doyle (1859-1930), English, author of The Adventures of Sherlock Holmes, “The Speckled Band” (1892), speaking of Dr. Grimesby Roylott.
For any number of obvious reasons it would probably be disquieting to folk at large to discover that Mother Theresa – to employ a fanciful illustration – had kept a Swiss bank account. One would imagine that the honesty of men working at the frontiers of science in that hazy twilight terrain between the known and the unknown, the certain and the speculative, would count for quite a bit as well. Particularly where their pontifications, theories, and advices have the potential both to reap magnificent honours and riches, and very directly affect us dumb fucks out in the laity who sit at the feet of these guys and crave as much of their wisdom as we can get. And especially in a time of a perceived medical emergency, or during the rise of an hysterical epidemic, fuelled by a medieval fear of tainted blood and poisoned semen – and now evil mothers’ milk – in which we look up with frightened eyes to these secular sages for deliverance from tiny invisible enemies which we are told beset us. Mostly when enjoying our favourite recreation.
Science at its outer limits is populated by no end of ambitious cowboys of modest acumen hungry for fame, glory and the Ferraris in which some of their lucky chums in bio-tech cruise out of their labs’ parking lots in the direction of their Cessna hangars. They live so to speak in remote Wild West towns with lamentably few marshals to keep an eye on things. These are the left-overs too mediocre to cut it in university environments who wind up in homes for scientific dullards like the politically powerful health bureaucracies of the National Institutes of Health and The Centres for Disease Control in the USA. As we’ve all seen, when these oracles mumble, press trumpets blare and the entire world eagerly gobbles up every word, without demur. Notwithstanding how many fake health crises they have delivered still-born into the popular consciousness, like the idle Herpes scare in the 70’s, the phantom Syphilis epidemic in the 30’s and 40’s, the great Swine Flu fiasco in the 60’s, and that shining emblem of medical idiocy, the Pellagra plague in the first four decades of this century, treated inter alia with arsenic and ruthless quarantine, which turned out to be plain malnutrition among the politically awkward droves of poor white crackers in deep south industrial towns.
We need contagious epidemics to fight. Even imagined ones. They’re tremendously psychologically useful. Germ theory so dominates contemporary medicine that it seeks germs everywhere, the more virulent the better, and especially if they can be linked to our culture’s great taboos, sex and death. Anything to avoid facing up to unappealing political realities like widespread chronic undernourishment among a shameful number of our countrymen as the time-honoured and common-sense cause of broken health. Or, at the other pole, for those of us felicitously occupying the higher orders, factors inextricably tied to the excesses of our culture of affluence.
Of course, the loftier the degree of scientific specialisation, the sharper the point of the pyramid, the smaller and remoter the frontier town, and the fewer the guys with badges. As in a funny little corner of theoretical (some say virtual) virology called retrovirology – served at the commencement of the AIDS era by only a handful of labs run by the same guys who’d lost the “war on cancer” declared by Nixon in 1971, by putting all their money, and 40 billion of their country’s, on the perfectly ridiculous theory that cancer was an infectious condition caused by viruses.
Folk inclined to the view that a reasonable degree of personal integrity is essential to serve as a brake on the perennial temptation tickling largely unpoliced scientists at the frontiers of their specialisations to make extravagant claims with fabulous commercial potential beyond those which their data really support might be put out to learn that the pope of AIDS is a complete scum-bag.
This is Robert Gallo, who told the worried world at a US Health Department-convened press conference on 23 April 1984, before the publication of any paper for his fellows to assess, that he’d discovered the cause, a virus he said, of the poor health that a narrow subset of gay men with ruinous lifestyles were experiencing, later christened, in a flourish of conceptual surplusage, the Acquired Immune Deficiency Syndrome. Having sneaked through a patent application on the blood test he’d devised for his claimed viral culprit ahead of the previously lodged French one, thus guaranteeing him a fortune in royalties, Gallo went on to publish four papers in the prestigious if dowdy journal Science two weeks later. Then the trouble started: an exuberant international disputation over who stole the fake diamonds. For Gallo this was the Paula trouble that led to Monica.
Luc Montagnier of the Pasteur Institute in France complained that the samples containing what he believed to be his newly spotted virus and which he’d trustingly sent Gallo had been flagrantly ripped off. He sued across the sea. Gallo brazenly counter-charged his accuser. It was embarrassing for the US administration to have its premier AIDS scientist accused of theft and fraud, but with the help of a gang of lawyers hired to fudge the facts and conceal boxes of crucial discoverable documents, Gallo got off – by dint of a neat political compromise agreeing a history, cosigned by no less than the presidents of the respective republics, Reagan and Chirac, in terms of which these two giants of modern biology were henceforth to be deemed co-discoverers of the AIDS virus.
The sham began unraveling almost immediately. A trouble-making investigative journalist on the Chicago Tribune, John Crewdson, began sticking his nose in. He went to print with a comprehensively researched expose spilling the beans on Gallo’s theft of Luc Montagnier’s samples, even his photographs of them. Hardly able to do otherwise, Gallo’s bosses in the National Institutes of Health instigated an enquiry with Yale biochemist Frederic Richards as overseer. Reviewing the four seminal research papers upon which the entire HIV-AIDS causation paradigm is founded – if feebly – the inquiry found fraud, a discrepancy between what had been reported and what had been done. The NIH watered it down, finding Gallo to his relief and the irritation of Richards, guilty merely of “creating and fostering conditions that gave rise to falsified/fabricated data and falsified reports”. This loyal whitewash was promptly criticized by Richards and by Senator John Dingle, who had got wind of the corruption in Gallo’s laboratory, and had begun his own investigation under the aegis of his Sub-Committee on Oversights and Investigations of the House Energy and Commerce Committee. The Department of Health’s Office of Research Integrity reviewed the NIH report and disagreed with the cop-out. It had no trouble finding Gallo guilty of scientific misconduct, the gravest possible verdict, and a capital offence in career terms. So did the Dingle Committee in its draft report. Facing criminal prosecution for the perjury adorning his patent application, Gallo was forced to leave the National Institutes of Health in disgrace. On the scandal festered, until 1993, when happily for Gallo, it all went away. The government dropped the patent charges, and of fraudulently making a misstatement in a scientific journal and failing to credit the work of other researchers in claiming it as his own. Why? Because, a review board, comprising lawyers naturally, not scientists, had raised the bar in asserting a brand-new revised definition of scientific misconduct, which Gallo’s prosecutors in the Office of Research Integrity doubted they could clear. Unlike Sol Kerzner who kept his head down when the bribery case against him was dropped, Gallo boasted complete vindication.
Before making becoming famous for HIV, Gallo’s laboratory had been found by a panel of university scientists appointed in 1974 to be one of the worst offenders in the scandalous abuse of federal funds received during the Cancer War. Two co-researchers were later gaoled for embezzlement.
*** (missing text) the founding papers of the most powerful, all-pervasive and terrifying medical model of our time, the HIV-AIDS-causation hypothesis. No wonder the Nobel committee has set its face against the whole stinking shambles. Yet its integrity is assumed as an indisputable fact of contemporary science in the almost one hundred thousand papers in the subject that have been published since. Those critics making a living in the scientific establishment who point a finger at the emperor’s pink arse do so at immense professional and personal risk, and for some, at terrible cost. But there’s another story.
Curiously, the Office of Research Integrity found that the fraud tainting Gallo’s claim-to-fame papers did not affect the validity of the papers’ main conclusions, even though some of the key research work was described as “of dubious scientific merit”, and “really crazy”. Suffice it to say that others who have meticulously scrutinized Gallo’s original HIV research claims – allowing for the purpose of reviewing them that the dubious research data is sound – have found them to be, well, shall we say troubling. The adventurous leap between the papers’ contents and their headings for starters. But that’s another yarn still.
Gallo’s disgraceful behaviour in relation to his AIDS research was no first. Had he not ascended to such power and influence within the federal health bureaucracy, it is likely that his claims to have found a single infectious cause for the disparate diseases grouped together as AIDS in the early 1980’s would have been laughed out of court. After all, this was the bright spark who, with almost as much fanfare as that at his flash-bulb popping HIV press announcement, had loudly touted his discovery of what he claimed to be the first identified human retrovirus, HL23V, in the mid 70’s. After another look, this exciting find turned out to be nothing of the kind, just an accidental laboratory artefact. His laboratory hadn’t done the most basic controls. To his great embarrassment, Gallo had to retract his fancy claims, and HL23V then modestly retired as a virus from the scientific lexicon.
As the last misfired shots were going off in the failed cancer war – staged largely around the viral-cancer hypothesis – and it had become irresistibly plain to everyone that cancer had nothing to do with germs, and the whole thing had been a monumental waste of money, Gallo and his mates (known in-house as the Bob Club) sought new funding opportunities for their imminently redundant laboratories. Ever eager to position himself where the action was, he began punting another retrovirus which he claimed to have discovered, HTLV1, as the possible cause of the odd diseases like Kaposi’s Sarcoma and Pneumocystitis Carinii Pneumonia suddenly appearing to ail urban fast-track life-style gay men in San Francisco and New York. The virus had in fact been identified by biologists in Gallo’s lab, principally Poiesz and Ruscetti, not Gallo, but true to form he appropriated the discovery and took the accolades. Wanting the virus to be all things, the theory that HTLV1 could be responsible for AIDS was ludicrous. He had previously claimed this virus, again on absurd grounds, to be the cause of a rare form of Leukaemia, which amounts to disorderly immune cell replication, not premature cell death. “One of the most exciting stories of twentieth century biology” he gushed. Nobel laureate Kary Mullis thinks it “a joke”. The virus had first been posited to be a cell division stimulant, not a killer. Obviously, Gallo’s new converse role for HTLV1 went up like a lead balloon, but it didn’t matter, because it wasn’t long afterwards that Montagnier sent Gallo his samples, and we know the rest. In cravenly seeking the imprimatur of Big American Science, by seeking the endorsement for his work of an abject rogue, Montagnier naively left his keys in the ignition, and the next thing it was gone. Gallo resprayed Montagnier’s LAV as HTLVIII. It was later renamed HIV, the Human Immunodeficiency Virus, on the basis of Gallo’s claims, without proof to warrant its fearsome title. (Unless one thinks that correlations disclose proofs of causation. As if sparrows sometimes seen on telephone cables cause crossed lines.)
Whether HIV (or rather the minute biological traces said to evidence its presence) actually lives up to its frightening billing, is something Gallo can’t seem to make up his mind about. This ought to come as some comfort to those who live in wait for the clatter of the hangman’s key. Once insisting that HIV “kills like a truck”, and “would kill Clark Kent”, he now concedes, “We don’t know that 100 percent of people infected with HIV will die with AIDS. We don’t know that. We shouldn’t be predicting that, and it could even precipitate suicide. They shouldn’t have put that on the front page (of the Washington Post), even if it were true. But the fact is that we just don’t know”. In 1995, The Pasteur Institute’s Simon Wain-Hobson confessed, “An intrinsic cytopathic effect of the virus is no longer feasible”. The biggest medical research effort in history has found HIV to be biologically inactive. Gallo has tried weaseling out of the difficulty created by this humbling observation by suggesting “cofactors” might be involved in AIDS, since HIV can’t do any mischief on its own. (David Ho’s opposite assertions in 1996 have imploded on his childish mathematical errors.) Gallo had lots to say about a virus called HHV8 for a while, implicated as a “co-factor” in the development of that signal AIDS condition Kaposi’s Sarcoma, but like all other exciting breakthroughs in AIDS research, it has proved to be just another flash in the pan. Worse still, it is now generally accepted, and by Gallo too, that those horrible skin blotches have nothing to do with HIV at all.
At last count, our charming charlatan was on SABC TV a few months ago, singing his own praises for his alleged breakthrough anti-HIV protein HAF, distilled from the urine of women with child. About which we have heard nothing since. Naturally, since it was just another rodeo stunt. Gallo’s new laboratory in Baltimore had produced nothing to show for the millions he had duped state and municipal authorities into giving him, and was about to have its plug pulled by the Maryland legislature accordingly. A neatly timed “very important discovery” defeated the danger.
Since the case for Gallo’s HIV-AIDS hypothesis is invariably pressed with calls to the authority of its famous protagonist, in the absence of scientific proof in the sense that most curious folk understand, it’s as well that we know what kind of bloke we’re relying on.
With such scintillating credentials as Gallo’s, no wonder the astute German virologist Stefan Lanka – referring to HIV-AIDS, Luc Montagnier, and Gallo – talks of “a medical theory concocted by a French mediocrity who, right from the start, doubted the validity of a virus-only theory of AIDS causation and only last week unleashed a new wave of doubt; and an American scientific gangster who had committed so many crass, self-aggrandising blunders in the previous decade, that he could not really be relied upon to tell the time correctly”. Quite.
Anthony Brink is an advocate (barrister) in Pietermaritzburg South Africa.