Should Wikipedia Be Trusted for HIV Retroviral Therapy?

David Crowe, Richard Gale and Gary Null PhD
Progressive Commentary Hour, October 4, 2019

Wikipedia’s entry for HIV prevention and treatment drug Zidovudine (ZDV), more commonly known as AZT (azidothymidine) and Retrovir, is largely a sanitized history about the discovery of by far the most important AIDS drug. The FDA’s approval of AZT established a new drug class of nucleoside analogs, sometimes referred to as “nukes.” It is also misleadingly referred to as a “reverse transcriptase inhibitor.” The history relies heavily upon pharmaceutical-sponsored research, such as the Burroughs-Welcome’s AZT trials that eventually led to its patent approval. On the surface, that is all fine. But as with many Wikipedia entries, it is the overriding message by the pages editors that require scrutiny. Vital information that ought to be included in an encyclopedic entry for a drug that has waged controversy ever since its discovery, is curiously missing. A review of AZT’s page history indicates that efforts to present the downside of AZT retroviral effectiveness and the drug’s safety record have been scrubbed. In fact, AZT is an incredibly dangerous drug, which we will see, directly interferes with DNA synthesis.

We might compare the Encyclopedia Britannica’s description of AZT with that found on Wikipedia. The latter has notable omissions. There are several important omissions that are otherwise found in the Britannica. Particularly notable is 1) AZT is only active against HIV when the virus is replicating into proviral DNA (viral DNA synthesized prior to integration into host DNA), 2) HIV is capable of mutating and thus of developing resistance to the drug, and 3) since AZT blocks certain human polymerase enzymes necessary for DNA synthesis it adversely affects mitochondrial DNA polymerase. “Muscle cells have very high numbers of mitochondria,” the Britannica states, “and AZT therapy can lead to the damage of muscle tissues, including the heart.”

For certain, the AIDS epidemic in the 1980s and 1990s launched an enormous scientific research and discovery effort to identify how the body’s immune system operates when challenged by a serious and largely unknown infection. As a result, today we have a far greater understanding about the immune system. Unfortunately, the pharmaceutical approach to treating viral infections, notably HIV, has been single-minded and has adhered to a one-size-fits-all course of treatment. Anti-viral drug therapy is little more than a horse race to kill a virus before it destroys the body. In the case of early nucleotide analogs, it was additionally a race as to whether the virus could be defeated before the drug killed the patient.

In 2000, The Guardian published an article looking back at the early days of retroviral drugs. The article quotes Trevor Jones, director general of the Association of British Pharmaceutical Industries, who recalls the confusion during the early years before Luc Montagnier at the Institut Pasteur identified and isolated the HIV virus. At that time, researchers were racing to find a drug to target a deathly disease, which they believed might be caused by a bacteria. Dr. Jones stated, “We weren’t looking for AIDS drugs, we were looking for compounds that would hit the DNA of bacteria, and we had made hundreds of these compounds.” Once the virus was identified, Jones continues, “we just opened up our store cupboards and said: these should work, because they will hit the

RNA of the virus. And they did.” But doing so was accompanied by a forewarning. Jones said, “Since DNA is a ubiquitous part of life, compounds that act against it can potentially stop life forms like bacteria, like viruses, like humans. Of course, they can cause cancer as well, so balancing the risks is an essential part of the fascination.”[1] And the anti-cancer drug selected was AZT. The Guardian notes that when AZT was first synthesized in 1964, it was shelved because it had proved too toxic to use against cancer” In other words, although AZT was too lethal for short term as a cancer drug, the drug industry and government health officials surmised it was quite fine for lifetime usage in the war against AIDS. Wikipedia editors whitewash over these facts by falsely claiming that the reason for AZT being shelved was because “it proved biologically inert in mice.” In fact, Dr. Jerome Horowitz who developed the compound would later state “it was a terrible disappointment…. we dumped it on the junk pile. I didn’t keep the notebooks. In fact, it was not even worth patenting.” AZT became such a standard in the fight against AIDS that later it would serve as the control for future AIDS drugs to replace a scientifically valid and inert placebo. In effect, the trials for bringing new AIDS drugs were primarily based upon determining whether these drugs were less toxic than AZT.

Before being released on the market, AZT was initially shown to be only effective against HIV in a petri dish was quickly released to the public. Yes, in a petri dish. Following two years of poorly designed and flawed human clinical trials, the FDA fast tracked AZT for approval and registration. Quickly the medical establishment recognized it as the most effective treatment against HIV infection and AIDS-related symptoms.

Wikipedia references a later Burrough’s double-blind, placebo controlled study as convincing proof that AZT “safely prolongs the lives of people with HIV.” However, a review of the study, published in a July 1987 issue of the New England Journal of Medicine, provides a dramatically different picture. The trial only recruited 282 participants and lasted 24 weeks. The trial also observed that “After 12 weeks, the number of CD4 cells declined to pretreatment values among AZT recipients with AIDS.” Moreover only 27 subjects completed the entire length of the study. Nobody with a medical background would dare cite such a study as a gold standard of “proof” of efficacy and safety except for Wikipedia editors.

Practically every drug on the market has its adverse effects, and this was especially true of AZT. Arguably AZT was one of the most toxic drugs ever developed in the pharmaceutical industry’s arsenal of treatments against an infectious disease.

Furthermore, during those early years of AZT therapy, studies about the drug’s life-threatening risks and numerous reports of serious adverse drug events were reaching the mainstream media. For some scientists and physicians, AZT was not the silver bullet that government health officials and the pharmaceutical industry had the public believing. Unfortunately these studies were largely ignored by the medical establishment. The pharmaceutical industrial complex was handed a colossal revenue opportunity as the epidemic worsened.

Some studies challenged the CDC’s and British health ministry’s faith in AZT and argued that it didn’t work at all. This is a narrative Wikipedia completely omits. But the most historically notable study was the British-French Concorde study, perhaps the largest AZT clinical trial ever conducted at that time and enrolled 1,749 patients over a three-year period. Early attempts to edit the Wikipedia page to include the Concorde study were removed. Rather than focus on patients displaying serious AIDS symptoms, the study included patients testing positive for HIV but who were not yet showing symptoms. The results were significant. Among those who took AZT group there were 169 deaths but only 3 among those who never took the drug. The AZT group also showed many more adverse effects. Although T-cell counts improved among those receiving the drug for a short period time, it eventually left CD4 cell counts less than before starting the regimen. The study concluded that AZT was a waste of time.

Medical journalist Celia Farber later reached out to the chief scientist behind the Concorde trial, Dr. Ian Weller, who had indicated “We’ve carried out this study against incredible adversity” and much of this came from the executives at Burroughs Wellcome.

This is vital information for anyone visiting Wikipedia to learn about AZT to have available. In its absence, Wikipedia’s entry for AZT is nothing more than a marketing essay.

Much has been written and can still be written about the dismal failures of retroviral treatment with a drug that had so little scientific support to validate its efficacy and safety. Another problem was that rising death rates being recorded as directly associated with the disease were not being distinguished from AZT toxicity, notably renal and liver failure. It was already known that the drug could produce AIDS-type symptoms. With AZT being overly prescribed, mortality rates leaped from 4,885 in 1988, a year after the drug was being launched, to 14,500 in 1989. Rates continued to climb steadily as new nucleocide reverse transcriptase inhibitor drugs entered the market. Mortality peaked in 1995 at over 48,000 deaths in the US alone.

Wikipedia would have us believe that AZT or azidothymidine is “the most effective and safe medicine needed in a health system” and repeats the World Health Organization’s claims that the drug is one of the “essential medicines” of our time. But does AZT really deserve such praise?

First, we might look at the adverse effects Wikipedia lists and compare it with actual evidence. The encyclopedia only mentions “nausea, vomiting, acid reflux (heartburn), headache, cosmetic reduction in abdominal body fat, light sleeping, and loss of appetite” and “faint discoloration of fingernails and toenails, mood elevation, occasional tingling or transient numbness of the hands or feet, and minor skin discoloration.” The page’s editors also undermine the drug’s more severe reactions of “anemia, neutropenia, hepatotoxicity, cardiomyopathy, and myopathy” by attributing it to the early days of AZT’s use and when it was administered in higher doses. These effects, according to Wikipedia, have seemingly been corrected by prescribing further drugs. However, based upon the manufacturer’s list of warnings, AZT is anything but safe and

its efficacy remains questionable, unless we need to completely redefine the meaning of “safety.” The manufacturer’s list of the drug’s adverse effects includes:

• Hematologic toxicity to bone marrow reserve
• Aplastic and hemolytic anemia and neutropenia
• Rapid reduction of hemoglobin
• Pancytopenia or reduction in red and white blood cells and platelets
• Myopathy and myositis with pathological changes
• Lymphadenopathy, an inflammatory disease of lymph nodes
• Lactic acidosis and severe hepatomegaly with steatosis (abnormal retention of lipids that affect the liver), including fatal cases
• Impairment of body’s ability to eliminate triglyceride fat
• Pancreatitis
• Increased Creatine Phosphokinase (CPK) that can lead to heart attacks
• Cardiomyopathy
• Hepatic decompensation — the development of jaundice, ascites, variceal hemorrhage, or hepatic encephalopathy
• Immune Reconstitution Syndrome – a paradoxical clinical worsening of a known condition or the appearance of a new condition after initiating antiretroviral therapy in HIV-infected patients
• Rhabdomyolysis – a severe syndrome resulting in the degeneration of muscle fibers that can lead to renal failure and death
• Stevens-Johnson syndrome – serious skin disorder associated with a drug reaction that has flu-like symptoms and blistering of the skin and requires hospitalization.

Other less life-threatening side effects indexed by AZT’s drug maker include asthenia, fevers and headaches, malaise, loss of mental acuity, seizures, anorexia, mascular edema, constipation or diarrhea, coughing, rhinitis and sinusitis, skin rashes, hearing loss, photophobia or an intolerance to light, nausea and vomiting.

The manufacturer further admits on its package insert that AZT may cause AIDS:

“It was often difficult to distinguish adverse events, possibility associated with the administration of Retrovir [AZT] from underlying signs of HIV disease or intercurrent illnesses.”

This happens to be what Wikipedia seemingly regards as a “safe” drug. And yet these lists of adverse effects above are woefully incomplete. The Alberta Rethinking AIDS Society has identified and gathered hundreds of peer-reviewed studies regarding the efficacy and adverse side effects of AZT and collected them into the most thorough reference library. Drawing upon the Society’s research, we can demonstrate further AZT’s health risks that Wikipedia ignores.

AZT and Cellular DNA
Wikipedia claims that AZT’s selectivity for targeting HIV reverse transcriptase “is due to the cell’s ability to quickly repairs its own DNA chain if it is disrupted by AZT during its formation, whereas the HIV virus lacks that ability.”

There are two fundamental problems with this claim. First, cells include mitochondrial DNA. Mitochondrial DNA is not protected by the cell’s nucleus DNA’s inherent repair mechanisms. One study concluded that “It appears that mitochondrial toxicity is responsible for most of the adverse effects of antiretroviral nucleoside analogues, since these agents can interfere with mitochondrial replication and function.”

Second, cellular DNA is much larger target than the HIV RNA; therefore, even if AZT is inefficient it will still attack the nuclear and mitochondrial DNA more than HIV RNA. Wikipedia does admit that “at sufficiently high doses, AZT begins to inhibit the cellular DNA polymerase used by mitochondria to replicate.” Yet there is no evidence that this only occurs at high doses. In fact, AZT does cause serious mitochondrial damage a lower doses. A listing of peer-reviewed studies showing this is the case can be found at the Alberta ReThinking AIDS Society’s website.

AZT Efficacy and Safety
As we noted above, Wikipedia states that AZT “is on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system.” First of all, the WHO should never be recognized as a global authority on any drug, whether the flu vaccine or AZT. It is an international organization fully captured by private industry.

Studies identifying AZT’s adverse effects are extensive. In addition to the ones noted above:

• AZT is notorious for being harmful to all types of blood cells, including red blood cells, and the white blood cells critical to the proper functioning of the immune system

• One of the characteristics of AIDS is muscle wasting, and this is produced by AZT. The heart is largely muscle, therefore it is no surprise to find an association between AZT and heart disease

• AZT’s effectiveness would mean less sickness and less death, but AZT is associated with more sickness and death

AZT and Cancer
Since AZT interferes with DNA replication, it is characteristically mutagenic and therefore can be expected to be associated with polymorphisms (i.e., mutations) that may progress into cancer. In 2009, California’s Environmental Protection Agency expanded its list of chemicals known to cause cancer or reproductive toxicity. The state’s proposition stated that “zidovudine (AZT) [is] being added to the list as known to the state to cause cancer.”[2] Certainly this warrants referencing on Wikipedia. Not only is it omitted but no reference to AZT’s mutagenic activity that may lead to cancer to mentioned.

In fact researchers had noted the AZT-cancer correlation shortly after the drug became the standard treatment of choice. A paper published in the Annals of Internal Medicine in 1990 concluded that “after starting antiretroviral treatment…the estimated probability of developing lymphoma …by 36 months, [was] 46.4% (CI, 19.6% to 75.5%)…a direct role of therapy itself cannot be totally discounted…Zidovudine [AZT] can act as a mutagen”[3]

AZT and Infants and Children
Wikipedia truthfully states that AZT “is often mandated for use by pregnant women.” These would be women who have tested positive for HIV. Sadly, women in developed countries, such as the US, are routinely threatened with the loss of custody of their children if they refuse to take AZT or give it to their newborn. The page, however, further states that the drug “appears to be safe for the baby.” AZT on the other hand is in no way safe for either the unborn fetus or infant.

A study published in the journal AIDS Research and Human Retroviruses observed that children coming to term from HIV-positive mothers on treatment had AZT “incorporated into fetal mitochondrial DNA from skeletal muscle, liver, kidney, and placenta.”[4]

A study published in the Journal of Acquired Immune Deficiency Syndrome reviewed cases of intentional or inadvertent use of AZT. There were eight spontaneous first trimester abortions, eight therapeutic terminations, and eight cases of fetal abnormality occurring among a total of 88 cases where the pregnancy progressed.[6]

A notable 1999 French study that followed the development of 8 uninfected infants treated with AZT because their mothers were HIV-positive, reported several of the life-threatening risks associated with the drug:

“Eight children with mitochondrial dysfunction were found…the first patient presented with visual impairment…[and] died aged 13 months because of respiratory and cardiac-rhythm disorders…The second patient, from age 4 months until death at 11 months, had refractory epilepsy and deterioration of cognitive and psychomotor abilities…At age 8 months…patient three had a seizure… In the fourth patient…between ages 14 and 27 months, the child had four episodes of febrile seizures…From age 7 months until 15 months, patient five had repeated seizures…at age 16 months…large necrotic lesions of the [brain]…At age 3-1/2 years the child had severe sequelae and microcephaly [abnormally small head]. Patient 6 was symptom-free until age 14 months, but persistent biochemical abnormalities were seen on standard follow-up…Patient 7 was symptom-free until age 4 months, at which time he became hypotonic [low muscle tone and stopped breathing]…The eighth child was symptom-free. Persistent hepatic and pancreatic abnormalities were seen from birth…At age 20 months, biological abnormalities persisted… cerebral NMR imaging…showed abnormalities of the periventricular white matter…No child was infected with HIV-1 [but because their mothers were HIV-positive] all children were treated after birth with zidovudine [AZT] alone or with zidovudine and lamivudine….The observation of several cases [of mitochondrial abnormalities] in a population of about 1700 exposed children strongly
suggests an acquired mitochondrial dysfunction…Pregnant women should be informed of the potential effects associated with these treatments during pregnancy.”[6]

There can be only one conclusion based upon these and many other studies: there is no strong scientific evidence that AZT is safe for a fetus, infant or children. Indeed, there is evidence that it is dangerous.

AZT as Preventative Medicine
Wikipedia claims that AZT, in concert with lamivudine, “substantially reduce[s] the risk of HIV infection following the first single exposure to the virus” — for example, if a person is exposed to HIV-positive blood. The entry does not reference a scientific paper but a CDC publication, which in turn does not reference a scientific paper. The entire message is that the current preferred regimen of AZT and lamivudine is safe and effective. Curiously, between 1984 (when HIV testing was initiated) through 1997 (the last year that the CDC reported on this issue), there was a grand total of zero documented cases occupational HIV transmission reported in surgeons, and zero in Emergency Medical Technicians/Paramedics, two groups most likely to experience uncontrolled exposures to HIV-positive blood.

Transmission of HIV and AIDS occupationally rarely happens although it should. Given that needle-stick injuries are frequent – it has been estimated that in the 1990s there were between 600,000 and 800,000 a year – it is surprising that occupational transmission of AIDS has hardly ever been documented. The logical conclusion is that occupational transmission of HIV is exceedingly unlikely. It is therefore exceedingly dangerous to promote a potentially lethal drug to prevent an event that essentially never happens.

Conclusion
There is no question that AIDS can frequently be a death sentence. Millions of people worldwide have been infected with the HIV virus and untold numbers have succumbed to this ravishing disease. Having a comprehensive understanding of all the best treatments, including those that are the most effective and safest, is essential for helping a victim survive.

Anyone who discovers that they are HIV positive or has AIDS, or knows someone with this life-threatening condition, will inevitably search for reliable information. Because of Wikipedia’s convenience and reputation, an inquirer will inevitably be directed to the online encyclopedia. Indeed, Wikipedia provides a hopeful review of AZT and relies mostly upon peer-reviewed scientific literature. Therefore, whether you are a physician, clinician or patient, Wikipedia now carries an aura of being a resource that is accurate, fair, and scholarly. This is the mythology Wikipedia has created and shrouded itself in.

However, during the past two years, a group of journalists. health activists, physicians, scientists and attorneys have shown that areas of health and alternative medical systems in particular, on genetically modified crops and pesticides, vaccines, etc, Wikipedia is not to be wholly trusted. It is not, in our opinion, by any means a legitimate and objective encyclopedia. Much of its content is not generated by highly recognized scholars in their fields, compared to the Encyclopedia Britannica, but rather by amateurs who more often than not conceal their true identities under anonymous names. Behind the scenes, there are powerful vested interests that determine and rule over the content for many of Wikipedia’s entries. These pages are filled with blatant biases, prejudices and even economic and ideological objectives that threaten the public.

We are investigating AZT for a specific reason. The Wikipedia editors’ research is subjective and its references are cherry-picked. It is difficult to believe that the page’s author(s) was ignorant of the extensive body of medical literature confirming AZT’s ineffectiveness and more serious long-term adverse effects. This is extremely dangerous and can have deadly consequences. It is our contention that Wikipedia’s entire editorial operation supports wrongful activities that endanger public health and should be held accountable.

ENDNOTES

1 Radford T. Tomorrow’s pharmaceutical scientists will be part of the revolution. The Guardian. 2000 Mar 30;5

2 Chemicals listed effective December 18, 2009 as known to the State of California to cause cancer or reproductive toxicity: wood dust, Zidovudine (AZT), Tert-Amyl Methyl Ether (TAME) and Ethyl-Tert-Butyl Ether (EBTE). OEHHA. 2009 Dec 18.

3 Pluda JM Yarchoan R, Jaffe ES, Feuerstein IM, Solomon D, Steinberg SM, Wyvill KM, Raubitschek A, Katz D, Broder S. Development of non-Hodgkin lymphoma in a cohort of patients with severe human immunodeficiency virus (HIV) infection on long-term antiretroviral therapy. Ann Intern Med. 1990 Aug 15 113(4) 276-82.

4 Gerschenson M Nguyen V, Ewings EL et al. Mitochondrial toxicity in fetal Erythrocebus patas monkeys exposed transplacentally to zidovudine plus lamivudine. AIDS Res Hum Retro. 2004 Jan 20(1) 91-100.

5 Kumar RM et al. Zidovudine Use in Pregnancy: A Report on 104 Cases and the Occurrence of Birth Defects. J Acquir Immune Defic Syndr. 1994 Oct; 7(10): 1034-9.

6 Blanche S Tardieu M, Rustin P, Slama A, Barret B, Firtion G, Ciraru-Vigneron N, Lacroix C, Rouzioux C, Mandelbrot L, Desguerre I, Rotig A, Mayaux MJ, Delfraissy JF. Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues. Lancet. 1999 Sep 25 354(9184) 1084-9