4.1. DNA terminators licensed as a cure. In 1987 the American and European illicit drug epidemic had been joined by a new epidemic of toxic legal drugs, the DNA chain-terminators, such as AZT, that are prescribed to hundreds of thousands of HIV-positives together with a litany of other orthodox and unorthodox anti-HIV/AIDS drugs (see 4.2. and Table 7). In America AZT was licensed in record time as an antiviral drug in 1987 by the Food and Drug Administration (FDA) based on studies conducted by its sister institutions from the Department of HHS, the National Cancer Institute 147 and the NIAID 148 together with the drug's manufacturer Burroughs Wellcome.
The fast approval of AZT" despite its inherent toxicity" was a major coup of AIDS researchers 149. By going public more aggressively than any other scientists before, American AIDS researchers from the NIAID, NCI and CDC had mobilized patients, homosexual AIDS risk groups and journalists to demand protection from the predicted AIDS explosion at any cost. As a result of this pressure the FDA and AIDS researchers fast-tracked first the approval of AZT and then that of ever-more untested anti-HIV/AIDS drugs 150. Surprisingly, all of these drugs were eagerly welcomed by the medical and public press and above all by unsuspecting AIDS patients. The politics behind the approval of AZT first by the FDA and the American medical orthodoxy, and then by the rest of the world has been described in two recent books, Good intentions 151 and Inventing the AIDS Virus 11.
AZT and other DNA chain-terminators are now used both as AIDS prophylaxis and therapy in the hope that they will terminate HIV DNA synthesis without terminating cell DNA synthesis 152. However, there are several problems with this optimistic plan:
1) The licensing study conducted in 1986 by the National Cancer Institute (NCI) and Burroughs Wellcome had erroneously underestimated the toxicity of AZT for human cells a 1000-fold 147! Although at least 7 independent studies have since pointed out this 1000-fold error 153-159, the recommended prescription dose has only been reduced 3-fold, from 1.5 g of AZT per day in 1987 to 0.5 g now 160, 161.
2) The initial success of the American clinical licensing study conducted by the NIAID and Burroughs Wellcome, that claimed a 19-fold reduced AIDS-mortality 148, could not be reproduced by numerous independent studies from other countries, including the UK 162, France 163, The Netherlands 164, Australia 165, and also not by an independent American study that was not supported by the NIAID and Burroughs Wellcome 166.
3) Contrary to the manufacturers information, DNA chain-terminators, such as AZT, ddI, ddC, 3TC and d4T, were not designed to kill viruses but to kill human cells. Most of them were originally synthesized over 30 years ago, long before AIDS was known, to kill human cells as cancer chemotherapy by terminating cellular DNA synthesis 167. Thus DNA chain-terminators are inevitably cytotoxic 149.
4) Even in the light of the HIV-AIDS hypothesis, AZT treatment as anti-HIV therapy is irrational. Since only about 1 in 1000 T-cells of AIDS patients is infected with HIV25, 26, 30-32, 168-170, AZT will kill 999 uninfected T cells for every one that is infected 149, 151, 171, 172. Such a therapeutic index predicts that AZT cannot be beneficial as an anti-HIV drug. Moreover, since HIV is postulated to cause AIDS by killing T-cells, it is irrational to kill the same HIV-infected cells twice " once with HIV and again with AZT 26.
5) Although AZT and other DNA chain terminators are prescribed since 1987 to healthy and ill HIV-positives for the rest of their lives, there are as yet no animal experiments that have ever tested to what degree these inevitably toxic substances accelerate death. Moreover, animal experiments would be necessary to determine how AZT and other anti-viral prescription drugs interact with the many recreational drugs that are, or have been, consumed by most AZT recipients " a question that none of the licensing studies has even addressed. It is therefore not possible to know how HIV-positives could possibly benefit from AZT's hypothetical anti-HIV effects in view of its certain cell toxicity.
As of 1996 the DNA chain-terminators are prescribed in combination with another group of experimental anti-HIVdrugs, the protease inhibitors, under new labels, that give the impression that these "cocktails" are entirely new treatments 29, 173-176. But the morbidity and mortality of the long-term consumption of protease inhibitors alone or in combination with DNA chain terminators have neither been determined in animals nor in humans. Surprisingly, the fate of the first two groups of AIDS patients that are claimed to have benefited by protease inhibitors published in two articles and two editorials in Nature in January 1995 has not been mentioned since 33, 34, 177, 178. The absence of any follow-up of these promising claims is particularly odd since Nature has published numerous articles on AIDS and protease inhibitors.
1) AZT and other DNA chain-terminators. Every year since 1987 about 200,000 HIV-positive people are prescribed AZT and other DNA chain-terminators as anti-HIV drugs for the rest of their lives 26, 173. Because of the high cost (about $10,000 per year) most AZT recipients are Americans or Europeans 26, 29.
As of 1996 about 1.8 million (200,000 HIV-positives per year over 9 years) Americans and Europeans have been on AZT for an average of 1 year. The one-year-average on AZT is derived from the fact that within one to two years the average AZT recipient succumbs to the toxicities of AZT and of recreational drugs, and that many drop out after only a few months due to unbearable drug intoxication 26, 160, 179. In the words of the HIV/AIDS establishment, "AZT loses its effect after a year or two because the virus becomes resistant" 180. The above estimate is compatible with the total of $2.5 billion in AZT sales by Glaxo/Burroughs Wellcome 181. Since the wholesale price for a daily dose of 500 mg AZT per person for one year is $2,000 26, $2.5 billion corresponds to 1.25 million patient-years of AZT prescriptions since 1987.
Since recreational drugs are acknowledged AIDS risks 14, 28, and since AZT is prescribed as AIDS prophylaxis and therapy, the epidemiology of AZT use is in fact similar to that of recreational drug use 104, 130, 182. Although national statistics are not available, numerous studies indicate that the vast majority of AZT recipients are adult male homosexuals, and that a minority includes HIV-positive hemophiliacs, intravenous drug users 87, 91, transfusion recipients and babies 23, 24, 38, 183 (see 7.8.). Only a few cases are from the general population 11.
Even unborn American and French children and their HIV-positive mothers are now treated with AZT to prevent perinatal transmission of HIV 45. Although the risk to such children of picking up HIV from their mothers is only about 25%, all HIV-positive mothers are injected with AZT during the second and third trimesters, as well as their babies for six weeks after birth to prevent HIV transmission. In other words 75% of developing fetuses of HIV-positive mothers are treated for 6 months with DNA chain-terminators, although they will never even pick up HIV; and their mothers are treated although they will not transmit HIV. The procedure has been promoted as a milestone in the prevention of AIDS 184, 185. But the teratogenic risks of AZT do not justify this optimistic pronouncement (see 4.3., 7.8.).
The point that AZT functions like all other chemotherapies by killing all growing cells unselectively has not been lost to its manufacturer Glaxo Wellcome. Using the license earned for AIDS therapy, Glaxo Wellcome has recently also cornered the lucrative chemotherapy market for AZT. The British magazine Continuum describes the situation with some sarcasm in December 1995:
AZT, commonly described in the annals of the AIDS literature as an "antiretroviral" that "targets HIV-infected cells" looks set to carve out a new role for itself " attacking leukemia and psoriasis. Both conditions involve abnormal proliferation of cells.
A study published in the New England Journal of Medicine by researchers from the University of Southern California reports the use of AZT with interferon-alpha in 19 patients with adult T-cell leukemia-lymphoma 186. The condition is said to be caused by HTLV-I, one of Robert Gallo's discoveries/inventions, a claim to be treated with caution therefore. They reported five remissions and 11 'major responses'. There was no control group. The logic goes that since AZT kills cells, particularly rapidly growing ones such as cancerous cells, then it will be effective. AZT was also used in a study of psoriasis sufferers by Madeleine Duvic of the University of Texas, Houston. In four out of 12 sufferers most of the psoriasis was cleared up. The theory to support the finding is that since AZT stops cell replication it slows skin proliferation, which is normally rapid. Other researchers have said there are better treatments already available for psoriasis (so don't rush out and buy shares in Glaxo Wellcome just yet).
Glaxo Wellcome must be commended for creative marketing (we don't think) producing a drug that can kill any rapidly replicating cells in one lot of patients, and selectively, so we are told, kill HIV-infected cells in another lot of patients. Is it a clever drug or clever marketing? These results will have the additional benefit of rapidly replicating AZT sales 187.
In view of this, one wonders how soon AZT will also be offered as an abortion pill, like methotrexate another chemotherapeutic drug 188. According to an FDA official the prescription of AZT as an abortion pill would not require a new license, because once approved by the FDA "it can be prescibed for dandruff" 189.
2) Other anti-HIV/AIDS drugs. The consumption of AZT and other DNA chain terminators by healthy HIV-positives at risk for AIDS and AIDS patients is typically supplemented by a bewildering list of further prescription and over-the-counter drugs. A list of 23 anti-HIV/AIDS drugs taken by 2801 American HIV-positives, including 524 AIDS patients, is recorded in Table 7 41. Nearly all of these HIV-positives were male homosexuals (83%) or intravenous drug users (12%) who took those drugs because they wanted to prevent or cure AIDS.
A study entitled "Polypharmacy Among Patients Attending an AIDS Clinic: Utilization of Prescribed, Unorthodox, and Investigational Treatments" describes even higher drug use by 189 HIV-positives from San Francisco of which 94% were male homosexuals and 2% were intravenous drug users 190. In telephone interviews 96% of these people reported prescription drugs, 67% over-the-counter drugs, 31% investigational drugs, 29% recreational drugs, and 29% "alternative" drugs. An average of 2.3 medications were taken simultaneously by healthy HIV-positives and 5.6 medications were taken simultaneously by those with AIDS symptoms. The authors of the study "conclude that use of polypharmacy among some AIDS clinic patients is common, could create an increased risk for adverse drug reactions, and may affect clinical drug trials."
Larry Kramer, the HIV-positive playwright and founder of the gay activist organization Act-Up, has described his own anti-HIV/AIDS polypharmacy under the title "Checking in, my chart" 191. Following the advice of several AIDS luminaries such as Anthony Fauci, David Ho, Joseph Sonnabend, Alvin Friedman-Kien and others, Kramer composed his own polypharmacy of 19 drugs for an annual price tag of $19,000 150. This chart includes: "AZT (AIDS), acyclovir [genital herpes], Zantac, colchicine [mitosis blocker], propranolol, spironolactone, myphyston [liver cirrhosis and hepatitis], Eucerin, Moisturel, Retin-A, mycolog, flucinonide, sulfacet-r, Nizoral [fungal dermatitis], Hisminal and Humbid [bronchitis], and Shaklee vitamins, zinc, NAC" and a "turquoise stone which a fortune teller, many years ago, advised" 191. Before developing AIDS and medical drug addiction, Kramer offered a client's eye-view of homosexual life-style, including a long list of the 56 most popular recreational drugs in his novel Faggots 6, 11.
The polypharmacy of the AIDS patient and activist Peter Di Giulio from San Francisco, who suffers from weight loss, chronic diarrhea, skin ailments, and neuropathy, even exceeds that of Larry Kramer. At an annual cost of just over $41,000 "Di Giulio has no choice but to organize his life around his medications": the DNA chain terminators d4T, 3TC (for HIV), Cytovene (for cytomegalovirus) and Zovirax (for herpes), the protease inhibitor Crixivan, the antifungals Diflucan and Septra (for PCP), anti-mycobacterials Biaxin and Myambutol, the anti-diarrheal Lomotil, Valium for anxiety, and an assortment of ten vitamins and supplements 192.
The polypharmacy of adult HIV-positives even extends to children. The treatments prescribed to an American group of 20 boys and 22 girls serve as an example. These children were originally diagnosed as HIV-positive only at 7 years of age, but were HIV-positive from birth due to perinatally acquired HIV 193. At the time of HIV diagnosis, 5 of 42 (12%) were also diagnosed with some AIDS-defining diseases. Yet all but 2 of the children were treated with anti-HIV/AIDS drugs. At an average of 11 years of age the following medications were administered to the children:
Considering the toxicity and mode of action of the DNA chain terminators, it is not surprising that to date the professional literature has yet to offer the first AIDS cure with AZT or the other anti-HIV drugs 11, 25. In 1993, the British-French Concorde trial, the largest controlled study of its kind, even buried the hope that AZT might prevent AIDS 199. Instead, the final report of the trial confirmed in 1994 that AZT is not only unable to prevent AIDS, but even increases the mortality of recipients by 25% compared to the untreated controls 160.
Once the ice of absolute control on AZT by the NIAID, NCI, and Glaxo/Burroughs Wellcome was broken by the non-American Concorde trial, a series of American and European studies confirmed and extended the predictable toxicity of AZT. Although in coded language and with disclaimers that a specific detrimental outcome does not discredit the presumed merits of AZT, these results show that AZT not only fails to prevent AIDS, but actually causes AIDS diseases and accelerates death (see 7.8):
1) An American study of intravenous drug users observed in 1993 that, "The rate of CD4 lymphocyte depletion did not appear to slow after the initiation of zidovudine therapy " results suggested that zidovudine users in this sample may have experienced more rapid CD4+ cell depletion" 87.
2) An Indian-English collaboration reported in 1994 that among 104 babies of AZT-treated pregnant women 8 aborted spontaneously, 8 were aborted "therapeutically" and another 8 were born with serious birth defects, including holes in the chest, abnormal indentations at the base of the spine, misplaced ears, triangular faces, heart defects, extra digits and albinism 200. Zidovudine users in this study may have experienced more rapid CD4+ cell depletion.
3) The American MAC study of 5000 male homosexual men observed that, "HIV dementia among those reporting any antiretroviral use (AZT, ddI, ddC, or d4T) was 97% higher than among those not using this antiretroviral therapy" 117.
4) Another analysis of the of homosexual men from the MAC study revealed that AZT treatment increased the risk of pneumonia 2 to 4-fold 201.
5) And four years after introducing AZT prophylaxis against AIDS 161, Paul Volberding et al. published in 1994 "the average time with neither a progression of disease nor adverse event was 15.7, 15.6, and 14.8 months for patients receiving placebo, 500 mg zidovudine, and 1500 mg zidovudine, respectively." 202. Thus even Volberding now confirms the Concorde study's conclusion that AZT does not prolong life or prevent AIDS, but instead accelerates AIDS.
6) An independent British study even found that AZT prophylaxis reduced survival from 3 to 2 years and also observed AZT-specific AIDS diseases, "wasting syndrome, cryptosporidiosis, and cytomegalovirus infection ... almost exclusively" in AZT-treated AIDS patients 203. This result confirmed Concorde's observation, in particular the 25% higher mortality of those on AZT.
7) The results of AIDS prophylaxis by AZT proved even more devastating for American hemophiliacs: The AIDS risk of hemophiliacs on AZT was 4.5 times higher and their mortality was 2.7 times higher than that of untreated controls 204.
8) The mortality of British HIV-positive hemophiliacs has increased even 10-fold since 1987, since most are subjected to AZT and other anti-HIV/AIDS treatments 22-24, 38, 183.
9) In 1996 an American study from the National Institute of Child Health and Human Development concluded that AIDS prophylaxis with AZT also harms children: "In contrast with anecdotal clinical observations and other studies indicating that zidovudine favorably influences weight-growth rates, our analysis suggests the opposite." 205.
10) Even before the Concorde study a rare publication critical of AZT by the NCI reported in 1990 that AZT increased the annual lymphoma risk 50-fold compared to untreated controls 198.
But despite the devastating evidence that AZT enhances morbidity and accelerates death by causing AIDS defining diseases on its own, the faith of the medical orthodoxy in FDA approved AZT seems unshakable. No news is bad enough to discourage AZT prescriptions 29, 173 (see 7.8.).
Nevertheless, recently a few mainstream AIDS doctors have openly registered dissent, although not in the form of dedicated articles. Says Jay Levy, professor of medicine at the University of California at San Francisco, "With all the hoopla about antiviral drugs, and you get any virologist aside and they'll say this is not how we are going to win, it's high time we look at the immune system" 206. Lecturing his medical students, another professor of medicine at the University of California at San Francisco, Donald Abrams, is even more direct according to a university magazine:
Despite the promising evidence, definitive proof of protease inhibitors' efficacy can be provided only by randomized clinical trials with placebo. Because new antiviral drugs are continuously being developed, conducting such trials is virtually impossible due to the reluctance of patients to continue treatment with and "old" drug. Abrams spent the first half of his lecture describing analogous problems during the testing and approval of AZT, the first drug used in AIDS therapy.
AZT, a nucleoside analog, belongs to a class of drugs that inhibit DNA polymerization by terminating growing DNA chains. The study which demonstrated that AZT might be of benefit was a placebo control trial begun in 1986 involving 288 patients. Although the study was originally intended to last 24 weeks, it was cut short and unblinded half way through because of statistically significant differences in deaths between the two groups.
Abrams lamented that although "18 more people made it to this arbitrary milestone of four to eight months after pneumocystis... I didn't feel that this was showing that we were prolonging survival." Abrams blamed the "very powerful rhetoric" of the emerging community of AIDS activists, who demanded an end to clinical trials. "Somebody should write a book about the impact of that decision on HIV clinical trials history," added Abrams "because everything changed because of that demand."
Abrams recounted his early misgivings about AZT, which loses its effect after a year or two because the virus becomes resistant. He was also disturbed by findings demonstrating that a high dose of AZT resulted in a smaller rise of CD4 cells than a lower dose. "Maybe if we just stop it altogether people will be better off," he said.
Members of the audience were surprised to learn of the paucity of solid, clinical research behind AZT and other nucleic acid chain terminators, which prevent infected T-cells from transcribing the RNA viral genome into DNA, thereby inhibiting viral pathogenesis. Abrams exposed the tragic farce of past AIDS research and therapy--people who thought they were doing something useful were actually wasting time and valuable resources.
How should the clinician apply the new therapies? Abrams described his approach with patients. "I have a large population of people who have chosen not to take any antiretrovirals since I've been following them since the very beginning... They've watched all of their friends go on the antiviral bandwagon and die, so they've chose to remain naive [to therapy]. More and more, however, are now succumbing to pressure that protease inhibitors are 'it'... We are in the middle of the honeymoon period, and whether or not this is going to be an enduring marriage is unclear to me at this time, so, I'm advising my patients if they still have time, to wait." 180.
The inevitable damage caused by AZT prescriptions is compounded by many of the concomitant medicines taken by most, if not all HIV-positive Americans with AIDS and at risk for AIDS (Table 7). For example, some of the antiviral drugs like ganciclovir and acyclovir are also DNA chain terminators that are nearly as toxic as AZT 207. As expected they were observed to produce "pancytopenia" 208 by killing hemopoietic cells, and to have "direct [toxic] effects on myeloid and erythroid progenitor cells" 152, 209. Moreover, even American AIDS researchers are concerned that many of the anti-infectives used as anti-HIV/AIDS drugs have "nephrotoxic, cytotoxic, and myelosuppresive [effects], such as amphotericin B, co-trimoxazole, dapsone, interferon, pentamidine, vincristine, flucytosine, adriamycin, vinblastine, and others [which] could potentially increase the risk of hematologic toxicities in patients being treated with ZDV [AZT]" 209. In other words these drugs are immunosuppressive because they intoxicate and kill immune cells.
As yet there are no placebo-controlled human or even animal studies in the literature on the toxic effects of protease inhibitors, although over 60,000 Americans are daily users of the most popular brand 210. However, the popular press acknowledges effects such as "suicidal thoughts, twitching, central nervous disorders"extreme nausea, hallucinations, intense trembling" after several months on the drug 192. And the HIV/AIDS researcher Jerome Groopman of the Beth Israel Medical Center in Boston informed Newsweek in December 1996 that, "some patients have been 'showing signs of the benefits wearing off'" " an effect that is termed "crashing" by the magazine. Even the surrogate markers of presumed benefits of protease inhibitors, like decreased "viral load" 33, 34, 177, are lost over several months as "viral load has shot back up again and no one knows why" 210.
4.4. Conclusions. Although AZT cannot prevent or cure AIDS, and although AZT and the other DNA chain terminators are among the most toxic drugs legally available, and although AZT is already known to cause AIDS diseases and accelerates death on its own, about 200,000 HIV-positive Americans are daily recipients of AZT. Most of these are healthy because there are no more than 50,000 to 75,000 American AIDS patients per year 3. In addition most, perhaps all American HIV-positives at risk for AIDS also take other "concomitant medications" 209 that have known immunosuppressive and other detrimental effects, such as cortisones, dapsone, pentamidine and others 152, 194. Furthermore, most HIV-positive and HIV-negative people at risk for AIDS also consume bewildering combinations and doses of recreational drugs (see 3.). In other words, most Americans at risk for AIDS and with AIDS are walking pharmacies, consuming excessive doses of toxic recreational and toxic medical drugs.