“…R everse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) is the key enzyme responsible for the synthesis of a double-stranded copy of the HIV genome that is subsequently integrated into the host chromosome during HIV infection. Treatment of HIV-1-infected patients with RT inhibitors such as 3=-deoxy-3=-azidothymidine (zidovudine, AZT) leads to selection of mutations in RT known as thymidine analogue resistance mutations (TAMs), which include M41L, D67N, K70R, L210W, T215Y or F, and K219Q or E. RTs containing various combinations of these mutations have an elevated excision activity that allows them to remove AZT monophosphate (AZTMP) and other chain-terminating nucleotides after they have been incorporated (1,2,10,33). Treatment of HIV-1-infected patients with (Ϫ)2=,3=-dideoxy-3=-thiacytidine (lamivudine, 3TC) or (Ϫ)2=, 3=-dideoxy-5-fluoro-3=-thiacytidine (emtricitabine, FTC) leads to selection of the M184I mutation in RT, which is rapidly replaced with M184V (7,25,52,57).…”