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==Mode of action==
[[Image:Azt pills.JPG|thumb|right|250px|AZT in oral and injectable form]]
Like other [[reverse transcriptase inhibitor]]s, AZT works by inhibiting the action of [[reverse transcriptase]], the [[enzyme]] that HIV uses to make a [[DNA]] copy of its [[RNA]]. Reverse transcription is necessary for production of the viral double-stranded [[DNA]], which is subsequently spliced into the genetic material of a target [[cell (biology)|cell]] (where it is called a [[provirus]]).<!--
  --><ref>{{cite journal | author=Mitsuya H, Yarchoan R, Broder S | title=Molecular targets for AIDS therapy. | journal=Science | volume=249 | issue=4976 | pages=1533–44 | year=1990 | pmid=1699273 | doi=10.1126/science.1699273}}</ref><!--
  --><ref>{{cite journal | author=Mitsuya H, Weinhold K, Furman P, St Clair M, Lehrman S, Gallo R, Bolognesi D, Barry D, Broder S | title=3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus ''in vitro''. | journal=Proc Natl Acad Sci U S A | volume=82 | issue=20 | pages=7096–100 | year=1985 | pmid=2413459 | doi=10.1073/pnas.82.20.7096 | url=http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=2413459}}</ref><!--
  --><ref>{{cite journal | author=Yarchoan R, Klecker R, Weinhold K, Markham P, Lyerly H, Durack D, Gelmann E, Lehrman S, Blum R, Barry D | title=Administration of 3'-azido-3'-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex. | journal=Lancet | volume=1 | issue=8481 | pages=575–80 | year=1986 | pmid=2869302 | doi=10.1016/S0140-6736(86)92808-4}}</ref>

The azido group increases the [[lipophilic]] nature of AZT, allowing it to cross [[cell membrane]]s easily by [[diffusion]] and thereby also to cross the [[blood-brain barrier]].  Cellular enzymes convert AZT into the effective 5'-triphosphate form. Studies have shown that the termination of the formed DNA chains is the specific factor in the inhibitory effect.

The triphosphate form also has some ability to inhibit cellular [[DNA polymerase]], which is used by normal cells as part of [[cell division]].<!--
  --><ref>{{cite journal | author=Furman P, Fyfe J, St Clair M, Weinhold K, Rideout J, Freeman G, Lehrman S, Bolognesi D, Broder S, Mitsuya H | title=Phosphorylation of 3'-azido-3'-deoxythymidine and selective interaction of the 5'-triphosphate with human immunodeficiency virus reverse transcriptase. | journal=Proc Natl Acad Sci U S A | volume=83 | issue=21 | pages=8333–7 | year=1986 | pmid=2430286 | doi=10.1073/pnas.83.21.8333}}</ref><!--
  --><ref>{{cite journal | author=Mitsuya H, Weinhold K, Furman P, St Clair M, Lehrman S, Gallo R, Bolognesi D, Barry D, Broder S | title=3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus ''in vitro''. | journal=Proc Natl Acad Sci U S A | volume=82 | issue=20 | pages=7096–100 | year=1985 | pmid=2413459 | doi=10.1073/pnas.82.20.7096}}</ref><!--
  --><ref>{{cite journal | author=Plessinger M, Miller R | title=Effects of zidovudine (AZT) and dideoxyinosine (ddI) on human trophoblast cells. | journal=Reprod Toxicol | volume=13 | issue=6 | pages=537–46 | pmid=10613402 | doi=10.1016/S0890-6238(99)00052-0 | year=1999}}</ref> However, AZT has a 100- to 300-fold greater affinity for the HIV reverse transcriptase, as compared to the human DNA polymerase, accounting for its selective antiviral activity.<ref>Mitsuya H, Weinhold KJ, Furman PA, et al: 3'-azido-3;-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus ''in vitro''. Med Sci 1985; 82:7096-7100.</ref> A special kind of cellular DNA polymerase that replicates the DNA in [[mitochondria]] is relatively more sensitive to inhibition by AZT, and this accounts for certain toxicities such as damage to cardiac and other muscles (also called [[myositis]]).<!--
  --><ref>{{cite journal | author=Collins M, Sondel N, Cesar D, Hellerstein M | title=Effect of nucleoside reverse transcriptase inhibitors on mitochondrial DNA synthesis in rats and humans. | journal=J Acquir Immune Defic Syndr | volume=37 | issue=1 | pages=1132–9 | year=2004 | pmid=15319672 | doi=10.1097/01.qai.0000131585.77530.64}}</ref><!--
  --><ref>{{cite journal | author=Parker W, White E, Shaddix S, Ross L, Buckheit R, Germany J, Secrist J, Vince R, Shannon W | title=Mechanism of inhibition of human immunodeficiency virus type 1 reverse transcriptase and human DNA polymerases alpha, beta, and gamma by the 5'-triphosphates of carbovir, 3'-azido-3'-deoxythymidine, 2',3'-dideoxyguanosine and 3'-deoxythymidine. A novel RNA template for the evaluation of antiretroviral drugs. | journal=J Biol Chem | volume=266 | issue=3 | pages=1754–62 | year=1991 | pmid=1703154}}</ref><!--
  --><ref>{{cite book | author=Rang H.P., Dale M.M., Ritter J.M. | title=Pharmacology | edition=3<sup>rd</sup> edition | publisher=Pearson Professional Ltd | year=1995}}</ref><!--
  --><ref>{{cite journal | author=Balzarini J, Naesens L, Aquaro S, Knispel T, Perno C, De Clercq E, Meier C | title=Intracellular metabolism of CycloSaligenyl 3'-azido-2', 3'-dideoxythymidine monophosphate, a prodrug of 3'-azido-2', 3'-dideoxythymidine (zidovudine). | journal=Mol Pharmacol | volume=56 | issue=6 | pages=1354–61 | year=1999 | pmid=10570065 | url=http://molpharm.aspetjournals.org/cgi/content/full/56/6/1354}}</ref><!--
  --><ref>{{cite journal | author=Yarchoan R, Mitsuya H, Myers C, Broder S | title=Clinical pharmacology of 3'-azido-2',3'-dideoxythymidine (zidovudine) and related dideoxynucleosides. | journal=N Engl J Med | volume=321 | issue=11 | pages=726–38 | year=1989 | pmid=2671731}}</ref>