Peter J Flegg,
Blackpool, UK, FY3 8NR
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Yet again a supporter of the Perth Group has made erroneous reference to work which supposedly supports its position (on this occasion the claim that zidovudine is not triphosphorylated). Jean Umber (27 August) directs us to a study conducted by a French group on ZDV (AZT) metabolites. He does not point us to the original paper, but a science update web page. This web page does not indicate AZT is not triphosphorylated, as Umber would have us believe, merely that some AZT is metabolised to d4T triphoshate (1). In fact the article actually shows a diagram with AZT triphosphate clearly marked in the metabolic pathway.
If one reads the original paper (something seldom done by HIV denialists), one finds that the authors clearly state AZT (ZDV) is known to be metabolized intracellularly into ZDV-TP (2). They measured ZDV-TP levels in 21 patients, finding it present in 20. They also did serial measurements of ZDV-TP in PBMC cultures after addition of ZDV, showing rising levels with time of incubation and initial ZDV dose. There are many other research papers which attest to the presence of ZDV-TP (3-5 are just a small sample).
Once again we see that research work supposedly supporting the Perth Group’s claims does nothing of the sort. I have a couple of suggestions for the Perth Group and its acolytes –
1. When quoting work to support a claim, it is a good idea to read the original paper first.
2. When referring to the paper, do not misquote or misrepresent the author’s findings.
3. Do not assume that readers of the BMJ will accept your word at face value – they are quite likely to go to the source and discover the author’s true thoughts on the matter.
1. http://www- dsv.cea.fr/content/cea_eng/avan/annee_2003/actu03_azt.htm
2. Becher, Francois; Pruvost, Alain G; Schlemmer, Dimitri D. et al. Significant levels of intracellular stavudine triphosphate are found in HIV-infected zidovudine-treated patients. AIDS 2003; 17: 555-561.
3. Becher F, Schlemmer D, Pruvost A, Nevers MC, Goujard C, Guerrero C, et al. Development of a direct assay for measuring intracellular AZT triphosphate in human PBMCs. Anal Chem 2002, 74:4220–4227.
4. Barry M, Wild M, Veal G, Back D, Breckenridge A, Fox R, et al. Zidovudine phosphorylation in HIV-infected patients and seronegative volunteers. AIDS 1994, 8:1–5.
5. Fletcher CV, Kawle SP, Kakuda TN, Anderson PL, Weller D, Bushman LR, et al. Zidovudine triphosphate and lamivudine triphosphate concentration-response relationships in HIV- infected persons. AIDS 2000, 14:2137–2144.
Competing interests: None declared