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Item #38: How Does AZT Work?

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Farber

AZT, which was developed as a chemotherapeutic agent in 1964 but shelved because of its extreme toxicity, is a DNA chain terminator, which means that it brings DNA synthesis to a halt. It is therefore an extremely efficient cell killer. HIV is a retrotirus, and as such replicates itself by inserting its genes into a cell's genome so that when the cell divides a new copy of the virus is produced. AZT prevents the replication of HIV by killing infected T-cells; unfortunately, it kills all dividing cells indiscriminately, whether they are infected with a retrovirus or not, and will very quickly decimate even a healthy person's immune system. AZT's manufacturer, GlaxoSmith Kline, chose not to comment for this article.

Gallo

Footnote 11 states that AZT is a DNA chain terminator and kills all dividing cells indiscriminately. Farber further states "AZT prevents the replication of HIV by killing infected T-cells". Apparently GlaxoSmithKline was asked to comment on this. If Harper's had an appropriate fact-checking process for scientific issues, it would have been realised that this should have been fact-checked with expert researchers, not the manufacturer of the drug.

AZT does not kill cells indiscriminately. At concentrations below those that are toxic to human cells, AZT interferes directly with HIV replication within the living, infected cell, by inhibiting the conversion of the viral RNA into DNA62 . A more detailed description of how AZT works is given in an endnote63 . AIDS researcher and clinicians do not claim that AZT is a perfect drug; undoubtedly it can and does cause side effects. As with most drugs used to treat, say, cancer, the therapeutic index for AZT is less than ideal, but the dangers of not treating HIV infection strongly outweigh the risks of doing so. AZT therefore remains a highly useful drug for HIV therapy. This has been shown in clinical trials and cohort analyses as demonstrated by several references in our endnotes.

RA

The literature on the toxic effects of AZT is voluminous. We have provided a survey detailing the shocking side effects (including death) at rethinkingaids.com/quotes/azt.html.

The Gallo document claims that “AZT does not kill cells indiscriminately” but then, buried in a footnote, describes accurately that AZT acts “as an analog of the DNA-component, thymidine”. This would mean that HIV can stop DNA synthesis, and thus cell division.

However, there is a scientific research review published in 1999 [1] shows that AZT is not triphosphorylated to a significant degree and therefore cannot have the claimed mode of action. Triphosphorylation is necessary to activate AZT and allow its incorporation into DNA.

The fact that AZT cannot interfere with viral transcription does not mean that it cannot have side effects. The fact that it has been noted by many authors that AZT does damage mitochondria, cellular energy-regulating organelles that have their own DNA and replicate independently, means that it is interfering with DNA synthesis, but not in the way claimed by the Gallo document.

It is particularly shocking that a drug that interferes with cellular and mitochondrial DNA synthesis should be prescribed to pregnant women and children. One paper published in 2003 recorded that “All the children with ‘established’ or ‘possible’ mitochondriopathy [mitochondrial damage] diagnosed in this study had been exposed to antiretroviral drugs. One of these children was treated with zidovudine [AZT] only during the prenatal period and received no treatment after birth…For the other children, the treatment was administered in the pre, per- and post-partum periods. It was zidovudine alone in five cases, a combination of zidovudine-lamivudine in 14 cases and another combination in one. 20 of the mothers received zidovudine by intravenous perfusion during labor.” [2]

The side effects of AZT lead to real, measurable clinical damage. Several studies have recorded conclusions similar to “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%).” [3]

It is not surprising to read papers with titles like “AZT is a Genotoxic Transplacental Carcinogen in Animal Models” [4]. Translated, this title means that, in monkeys and mice, AZT damages DNA, causes cancer, and crosses the placenta from mother to her offspring.

The Gallo document closes by stating “AZT therefore remains a highly useful drug for HIV therapy. This has been shown in clinical trials and cohort analyses as demonstrated by several references in our endnotes.” They do not specify what those references are.

Refs.

  1. 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.
  2. Barret B et al. Persistent mitochondrial dysfunction in HIV-1-exposed but uninfected infants: clinical screening in a large prospective cohort. AIDS. 2003 Aug 15; 17(12): 1769-1785.
  3. 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.
  4. Olivero OA et al. AZT is a Genotoxic Transplacental Carcinogen in Animal Models. J Acquir Immune Defic Syndr. 1997 Apr 1; 14(4): A29.

© Copyright December 9, 2008 by Rethinking AIDS.