Theoretical mechanistic basis of the toxic effects and efficacy of AZT in HIV: AIDS

Abstract 

Toxic effects and efficacy of azidothymidine (AZT) in human immunodeficiency virus were evaluated by theoretical mechanistic biochemistry (TMB) techniques based on the structure of AZT and on the structure of HIV. AZT was positive (1+) for epoxide; (2+) for hydroxl free radical (); (1+) for () azide free radical and (1+) for azide (N₃⁻) generations, respectively. AZT was negative (−) for areneimine, and nitroso generations, respectively, for toxic effects totalling 5+ compared with dideoxycytidine (ddc) of 3+ and artesunate (At) of 0.

Therefore for toxic effects the trend is AZT(5+)>ddc(3+)>At(0). TMB efficacy of AZT was based on the generations of from the 1-NH (1+) and the 3¹-azido (N₃)(1+) and azide free radical (), (1+) totalling 3+ compared with ddc of 1+ and At of 1+. Therefore for efficacy, the trend is AZT(3+)>ddc(1+)=At(1+). In combination drug therapy, TMB postulates the following for HIV : AIDS: At(1+)+AZT(3+)+ddc(1+)>AZT(3+)+ddc(1+)=AZT(3+)+At(1+)>AZT(3+)>At(1+)+ddc(1+)>ddc(1+)=At(1+).