A Critical Analysis of the Pharmacology of AZT and its Use in AIDS

摘要: Summary The triphosphorylated form of the nucleoside analogue 3’-azido-3’-deoxythymidine (Zidovudine, AZT) is claimed to interrupt HIV replication cycle by a selective inhibition viral reverse transcriptase, thereby preventing formation new proviral DNA in permissive, uninfected cells. Given that initial infection an individual instigates abundant from inception until death, and life infected T-cells only several days, administration AZT should lead both vitro vivo (i) decreased DNA; thus (ii) frequencies ‘HIV isolation’ (detection p24 or transcription both) stimulated cultures/cocultures seropositive individuals; (iii) synthesis RNA (‘antigenaemia’, ‘plasma viraemia’, ‘viral load’) ultimately resulting low absent levels all three parameters; (iv) perfect direct correlation between these parameters. A critical analysis presently available data shows no such evidence exists, outcome not unexpected given pharmacological on AZT. experts agree (AZTTP) unphosphorylated administered patients, nor its mono- diphosphate, active agent. Furthermore, mechanism action ability AZTTP halt HIV-DNA (chain termination). However, although this claim was posited outset, underwent clinical trials introduced as specific anti-HIV drug many years before there were any proving cells patients are able triphosphorylate parent compound level considered sufficient for putative action. Notwithstanding, published since 1991 it has become apparent phosphorylation takes place cannot possess effect. scientific literature does elucidate: number biochemical mechanisms which predicate likelihood widespread, serious toxicity use drug; significant antibacterial antiviral properties confound interpretation effects when patients. Based difficult if impossible explain why still remains most widely recommended used drug.