AZT; Azidothymidine; Retrovir® ZDV; Zidovudine;

AZT was one of the first nucleoside analogs shown to have potent anti-HIV activity in-vitro (1). AZT enters cells by passive diffusion, and appears to be phosphorylated by the same enzymes that convert thymidine (dT) to dT-5'-TP. AZT-triphosphate (AZT-TP) is the active species, acting as a chain terminating substrate for HIV reverse transcriptase (HIV-RT) during either first or second strand DNA synthesis.
Although resistance to AZT frequently develops, the addition of 3TC (Lamivudine) to a therapeutic regimen can cause AZT-resistant strains to revert to AZT-sensitive strains (4).
In-vitro Data
Cell
Strain
EC50^
IC50^^
Units
TI^^^
Reference
PBMC (PHA STIM.)
HIV-1(IIIB)
0.05
>50
µM
>1000
1
ATH8
HIV-1(IIIB)
1-5
>10
µM
>10
1
MT4
HIV-1(IIIB)
0.006
4
µM
667
2
PBL(PHA STIM.)
HIV-1(IIIB)
0.09
14*
µM
156
3
PBL(PHA STIM.)
HIV-1(CLINICAL ISOLATES (MEAN OF 54))
0.23
0.3**
µM
1.3
3
HeLa CD4+
HIV-1(HXB2-D)
0.01
-
µM
-
4
HeLa CD4+
HIV-1(HIVRTMN (RT-M41L,T215Y))+
0.7
-
µM
-
4
HeLa CD4+
HIV-1(HIVRTMN P9(RT-M41L,T215Y))++
1.36
-
µM
-
4
HeLa CD4+
HIV-1(HIVRTMN P10(RT-M41L,T215Y, M184V))#
0.01
-
µM
-
4^EC50 (also commonly referred to as ED50 or IC50) is the effective concentration that inhibits 50% of viral production, 50% of viral infectivity, or 50% of the virus-induced cytopathic effect.
^^IC50 (also referred to as CC50, CD50; TC50,TD50 or cytotoxicity) is the inhibitory concentration that reduces cellular growth or viability of uninfected cells by 50%.
^^^TI (also known as SI or selectivity index) is the therapeutic index which is equal to IC50/EC50.
*IC50=% Inhibition granulocyte.-macrophage colony formation of human bone marrow progenitor cells
**IC50=% Inhibition erythroid blast forming units of human bone marrow progenitor cells
+AZT resistant strain
++AZT resistant strain passaged 9X in 5 µM AZT and increasing conc.entrations of 3TC (Final conc.=50 µM).
#AZT resistant strain passaged 10X IN 5µM AZT and increasing concentrations of 3TC (Final conc.=100 µM); M184V mutation is also seen in most patients after six weeks of AZT/3TC combination therapy and is associated with the conversion of an AZT resistant strain to an AZT sensitive strain.