Rate of thymidine analogue resistance mutation accumulation with zidovudine- or stavudine-based regimens.

Zidovudine (ZDV) and stavudine (d4T) select for the same set of thymidine analogue resistance mutations (TAMs). To compare the rate at which TAMs emerge, genotypic analysis of HIV-1 was performed on serial plasma samples from treatment-naive subjects randomly assigned to receive ZDV or d4T in combination with lamivudine. After 72 weeks of follow-up, TAMs were detected in samples from 50% of ZDV-treated subjects and 45% of d4T-treated subjects (P = 0.79). The frequency of K70R and T215Y or F mutations was similar in both groups, although M41L was observed more frequently in samples from ZDV-treated subjects. This randomized study shows that TAMs accumulate at similar rates during treatment with ZDV or d4T, but the specific pattern of mutations may differ somewhat in patients treated with these thymidine analogues.