The AZT Wikipedia Page – Unsafe Despite the Lies

David Crowe
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January, 2020

This article was written at the request of Gary Null. No attempt to modify the Wikipedia page to correct the inaccuracies was made because it is well known (from bitter experience) that anonymous Wikipedia editors will reverse any changes, and will ban the contributor if they try to persist. This is the subject of legal action between Gary Null and others and Wikipedia. An earlier version was broadcast on Gary Null's Progressive Commetary Hour in October, 2019, on PRN.FM.

AZT, also known as Azidothymidine and Retrovir, is by far the most important AIDS drug. It was the first prescribed, after its rapid approval by the FDA in 1987, it established its class, nucleoside analogs (‘nukes’), as the backbone of AIDS prescriptions, and it is often mandated for use by pregnant women. AZT was also the ‘control’ used in many trials of later AIDS drugs to avoid the use of a placebo. And yes, the original trials of AZT were highly corrupted, so all a comparison of a newer drug against AZT proved was that the newer drug was less toxic than AZT, not that it was safe and effective.

AZT is also an incredibly dangerous drug because it directly interferes with DNA synthesis. DNA is composed of four bases, aka nucleosides: Adenosine, Cytosine, Guanine, Thymidine. The “T” in AZT stands for “Thymidine”. AZT is similar to the nucleoside Thymidine, hence the term “nucleoside analog” for this class of drugs (also used with similar risks in other diseases such as Hepatitis C and SARS).

If DNA is analogized to a chain of beads, each of which joins to the chain at one end, and then allows another bead to join at the other end, AZT is a broken bead, that does not allow the building of the chain to continue. Hence the name, “DNA chain terminator” for this class of drugs.

AZT is also referred to as a “Reverse Transcriptase Inhibitor” but, unlike “nucleoside analog”, this is not an accurate name, as I will show later.

This is enough background to start to understand the most egregious lies in the Wikipedia AZT page:

https://en.wikipedia.org/wiki/Zidovudine

I will only address some of the concerns about this page, but for further research, please consult my annotated and categorized list of scientific citations about this drug and of combinations, which often include AZT, even today, especially in developing countries:

http://aras.ab.ca/azt.html

http://aras.ab.ca/haart.html

CLAIM: AZT is safe for babies

Wikipedia states that, “[AZT] is commonly used in pregnancy and appears to be safe for the baby.” Sadly, the first part of the sentence is true. In fact, women in rich countries are routinely threatened with loss of custody of their children if they refuse to take AZT (or to give it to their newborn). They are faced with a Catch-22, harm themselves and their baby, or someone else will harm their baby.

From my page of citations related to AZT and mothers, fetuses and babies at http://aras.ab.ca/azt-perinatal.php :

• “In a series of 104 cases of intentional or inadvertent use of zidovudine at differing gestations in pregnancy, 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” (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.).
• “In HIV-infected pregnant women treated with two RTI [Reverse Transcriptase Inhibitors or nucleoside analogs, of which AZT was the most common] with or without protease inhibitors, one or more adverse events occurred in 29 out of 37 women and in 14 out of 30 babies.” (Lorenzi P et al. Antiretroviral therapies in pregnancy: maternal fetal and neonatal effects. AIDS. 1998; 12: F241-247.)
• “Comparison of HIV-1-infected children whose mothers were treated with ZDV [AZT] with children whose mothers were not treated showed that the former group had a [1.8 times] higher probability of developing severe disease or severe immune suppression [2.4 times higher risk] and a lower survival (72.2% versus 81.0%)” (The Italian Register for HIV Infection in Children. Rapid disease progression in HIV-1 perinatally infected children born to mothers receiving zidovudine monotherapy during pregnancy. AIDS. 1999 May 28; 13: 927-33.).
• “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 until death at 11 months, had refractory epilepsy and deterioration of cognitive and psychomotor abilities...(etcetera)…all children were treated after birth with zidovudine [AZT] alone or with zidovudine and lamivudine [also a nucleoside analog]. Treatment continued for 6 weeks in four children and was stopped prematurely because of haematological or biochemical intolerance in four children...The observation of several cases [of mitochondrial abnormalities] in a population of about 1700 exposed children [as compared with 1/5,000 to 1/20,000 in normal populations] strongly suggests an acquired mitochondrial dysfunction.” (Blanche S et al. Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues. Lancet. 1999 Sep 25; 354(9184): 1084-9.)
• “Children treated with zidovudine continued to have bacterial and opportunistic infections...One or more episodes of hematologic toxicity occurred in 54 children (61%)—anemia (hemoglobin level, <75g per liter) in 23 children (26%) and neutropenia (neutrophil count, <0.75X10^9 per liter) in 42 (48%)” (McKinney RE et al. A multicenter trial of oral zidovudine in children with advanced human immunodeficiency virus disease. N Engl J Med. 1991 Apr 11; 324(15): 1018-25.).
• “After adjusting for prematurity and maternal clinical characteristics, RPD [rapid disease progression] was three times more likely to occur in infants born to [mothers] treated [with AZT] compared with findings in untreated mothers (RR=2.8; p = .021).” (de Souza, 2000)
• “Our results…suggested that infected infants who were perinatally exposed to ZDV [AZT] may have a more rapid early disease progression with unfavorable viral manifestations than those without exposure to antiretroviral drug…There were 6/12 (50%) infants who developed symptoms at the age 6 months. Of these rapid disease progression, five (83.3%) were infants in group Z [whose mothers used AZT] and one was in group C [mothers did not take AZT…The clinical symptoms of these infected infants included oral thrush (4/6), dermatitis (1/6), splenomegaly [enlarged spleen] (5/6), hepatomegaly [enlarged liver] (5/6), and lymphadenopathy (3/6).” (Sutthent R et al. Effect of perinatal short-course zidovudine on the clinical and virological manifestations of HIV-1 subtype E infection in infants. J Clin Virol. 2002 Jul; 25(1): 47-56.)

Conclusion: False. AZT is not safe in babies.

CLAIM: AZT Works by Inhibiting the Enzyme Reverse Transcriptase

Reverse transcriptase is an enzyme that can take a chain of RNA and transcribe it into a chain of DNA, inserting it into a larger chain of DNA in the process. Since this is the reverse of the normal process, it is known as Reverse Transcription, and the enzyme as Reverse Transcriptase.

Reverse transcriptase operates on a nucleoside (such as Thymidine or AZT) with a molecule of ATP (containing three phosphates). Normally, the nucleoside will be added to the DNA chain, along with one phosphate, with two reclaimed. But the process cannot occur unless the three phosphates are added momentarily.

A scientific review of the evidence for AZT phosphorylation, which is necessary for this process, shows that mono-phosphorylation (addition of one phosphate) happens easily, but the necessary tri-phosphorylation rarely happens. Apart from not being able to block Reverse Transcriptase, another stunning conclusion is that AZT cannot be integrated into growing DNA chains. (Papadopulos-Eleopulos E et al. A Critical Analysis of the Pharmacology of AZT and its Use in AIDS. Current Medical Research & Opinion. 1999; 15: S1-45.)

One might assume that if AZT could not inhibit DNA chains by inserting itself into the chain, it also could not be toxic. However, the authors of this paper note that because of the efficient mono-phosphorylation, the drug could reduce the availability of this critical cellular resource, and cause toxicity in other ways. They authors also note that, “it is a well-known fact that AZT inhibits mitochondrial DNA (mtDNA) replication”. Mitochondria are critical organelles that are essentially separate life forms, that have their own DNA, and are critical for the regulation of energy in the cell (including providing the ATP that is necessary for construction of DNA chains).

Conclusion: Mostly false. AZT is not efficiently incorporated into DNA chains by Reverse Transcriptase

CLAIM: AZT does not disrupt cellular DNA

Wikipedia claims that the selectivity of AZT for HIV Reverse Transcriptase, “is due to the cell's ability to quickly repair its own DNA chain if it is disrupted by AZT during its formation, whereas the HIV virus lacks that ability.”

There are two serious problems with this claim. First of all, DNA in the cell includes mitochondrial DNA, which is not protected by the repair mechanisms for the DNA in the nucleus. Secondly, the cellular DNA is so much larger than HIV, that even if it is an inefficient target, it will still be hit more than HIV.

Wikipedia does admit that, “At sufficiently high dosages, AZT begins to inhibit the cellular DNA polymerase used by mitochondria to replicate”, but there is no reason to think that this would only occur at high doses. In fact, AZT does cause serious mitochondrial damage: http://aras.ab.ca/azt-mitochondria.php

Conclusion: False. AZT does disrupt cellular DNA

CLAIM: AZT is safe and effective

Wikipedia writes that, “[AZT] is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.” Again, the first part of the sentence is true, but inclusion on a WHO list is not proof that the drug is safe and effective.

The evidence of serious adverse effects of AZT is too extensive for this paper, so I will just refer you to the major categories of scientific citations that I have accumulated:

• 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: http://aras.ab.ca/azt-blood.php
• Animal models allow for experiments that would not be ethical on humans and have shown a wide variety of side effects, including the generation of cancers: http://aras.ab.ca/azt-animals.php
• AZT is highly associated with cancer, in fact it is registered as a carcinogen in the State of California: http://aras.ab.ca/azt-cancer.php
• Effectiveness would mean less sickness and less death, but AZT is associated with more sickness and death: http://aras.ab.ca/azt-sicker_n_deader.php
• As noted above, AZT is toxic to mitochondria, and mitochondrial disorders are severe, with a wide variety of side effects: http://aras.ab.ca/azt-mitochondria.php
• One of the characteristics of AIDS is muscle wasting, and this is produced by AZT. The heart is largely muscle, so it is no surprise to find an association between AZT and heart disease: http://aras.ab.ca/azt-muscle.php
• There are a wide variety of other diseases associated with the use of AZT: http://aras.ab.ca/azt-general.php
• One of the largest studies of AZT, the so-called Concorde study, showed 3 deaths in people who had only taken placebo, and 169 in people who had taken some AZT. (Concorde Coordinating Committee. Concorde: MRC/ANRS randomised double-blind controlled trial of immediate and deferred zidovudine in symptom-free HIV infection. Lancet. 1994 Apr 9; 343(8902): 871-81.)
• The manufacturer notes that the side effects of AZT are the symptoms of AIDS: “It was often difficult to distinguish adverse events possibly associated with administration of RETROVIR^® (AZT™) from underlying signs of HIV disease or intercurrent illnesses” (Retrovir product monograph. GlaxoSmithKline. 2001 Aug 14.)

Conclusion: False. AZT is not safe and effective

CLAIM: The use of AZT is cheap

Wikipedia notes that, “The wholesale cost [of AZT] in the developing world is US$5.10 to $25.60 per month.” This is a claim that is true if just the cost of the drug is considered, but the side effects require expensive monitoring, plus expensive treatments.

For example, anemia is one of the most frequent side effects, and even Wikipedia notes that, “Anemia due to AZT was successfully treated using erythropoetin to stimulate red blood cell production.” Ignoring the questionable use of the word “successfully”, erythropoietin is an (expensive) chemical that stimulates red blood cell production. This cost is not included in the Wikipedia cost claim, nor are the costs of monitoring for organ damage, organ transplants, and necessary services such as hospital stays and wheelchairs for those who suffer serious side effects.

Back in 1990, a year’s supply of erythropoietin cost $4000, according to the LA Times. Current advertising from companies in Hong Kong and China state that 20 iu (international units) are required per kg body weight, 3 times per week, and the price is US$80-US$120 per 3000 iu (depending on quantity). Assuming the lowest cost, and a weight of 90kg for a man, the cost is now about US$7500 per year.

Conclusion: False. The use of AZT is not cheap

CLAIM: AZT Reduces Infection Risk after Exposure

When someone is exposed to the blood of an HIV-positive person, e.g. due to a needle-stick injury, they were often given AZT for PEP (post-exposure prophylaxis). Wikipedia claims that AZT, in concert with lamivudine, “substantially reduce[s] the risk of HIV infection following the first single exposure to the virus”. Wikipedia does not reference a scientific paper, but a CDC publication which, in turn does not reference a scientific paper showing that their current preferred regimen of AZT and lamivudine is safe and effective.

One study in children and adolescents noted, “The regimens used for PEP [post-exposure prophylaxis] included zidovudine [AZT], lamivudine [3TC], and indinavir in seven patients [children from 2 to 20], and zidovudine, lamivudine and nelfinavir in one patient. In two patients PEP was offered but never begun…Of the 8 patients who initiated PEP only two completed the prescribed 4-week regimen…The reasons…included side effects…4 of the 5 patients who received a full or partial course of PEP and could be followed reported significant side effects including four with nausea, vomiting, diarrhea, and abdominal pain and development of a rash in one individual” (Babl FE et al. HIV postexposure prophylaxis for children and adolescents. Am J Emerg Med. 2000 May; 18(3): 282-7.)

Another study showed that 85% of people stopped taking PEP before the full 28 day course due to intolerable side effects (Rabaud C et al. Tolerability of postexposure prophylaxis with zidovudine, lamivudine, and nelfinavir for human immunodeficiency virus infection. Clin Infect Dis. 2001 May 15; 32(10): 1494-5.).

But, in any case, transmission of AIDS occupationally rarely happens, although it should, as it was estimated that 600,000-800,000 needlestick injuries occured in the US alone in the 1990s (NIOSH Alert: preventing needlestick injuries in health care settings. DHHS (NIOSH). 1999 Nov; 2000-108.). A Brazilian study found that over 50% of surgical gloves had perforations after surgery, and this was not known to the medical workers, because gloves that were discarded because they were known to be perforated were not included in the study (Barbosa MV et al. Risk of glove perforation in minor and major plastic surgery procedures. Aesthetic Plast Surg. 2003 Nov-Dec; 27(6): 481-4.).

Despite this, between 1984 (when HIV testing was initiated) through 1997 (the last year that the CDC reported on this issue), a grand total of 0 cases of documented occupational HIV transmission had been reported in surgeons, and 0 in Emergency Medical Technicians/Paramedics, two of the groups most likely to experience uncontrolled exposures to HIV-positive blood (HIV/AIDS surveillance report for 1997. CDC. 1998; 9(2)).

In summary, the risk of occupational HIV transmission is extremely low, and a study to show that PEP is effective would be completely unethical (you would have to expose people to HIV-positive blood subcutaneously, and half the people would have to be given a placebo). It is known, on the other hand, that PEP is dangerous, as shown by the high rate of cessation among people to which it is prescribed.

For more science related to PEP see: http://aras.ab.ca/haart-PEP.php

Conclusion: Uncertain. AZT has not been shown to reduce infection after exposure

Conclusions

This is not a complete analysis of all the errors in the Wikipedia AZT page, there are probably many more. Given the high quality of the English, and the accuracy of claims that do not put AZT in a negative light, it is hard to believe that the authors were ignorant of the extensive literature showing that AZT is not effective, and is highly unsafe.