In HIV-1, development of resistance to AZT (3′-azido-3′-deoxythymidine) is mediated by the acquisition of thymidine analogue resistance mutations (TAMs) (i.e. M41L, D67N, K70R, L210W, T215F/Y and K219E/Q) in the viral reverse transcriptase (RT). Clinically relevant combinations of TAMs such as M41L/T215Y or D67N/K70R/T215F/K219Q enhance the ATP-mediated excision of AZT monophosphate (AZTMP) from the 3′ end of the primer, allowing DNA synthesis to continue. Additionally, during HIV-1 maturation, the Gag polyprotein is cleaved to release a mature ...