Genotypic correlates of a virologic response to stavudine after zidovudinemonotherapy

Prior evidence suggests that resistance to zidovudine (ZDV) confers some de gree of cross-resistance to stavudine (d4T), but no genotypic correlates of clinical d4T susceptibility and resistance exist. To identify the genotypi c correlates of a virologic response to d4T, reverse transcriptase (RT) seq uencing of archived plasma HIV isolates was performed on 31 subjects who re ceived d4T monotherapy in the AIDS Clinical Trials Group 302 study, all of whom received more than 3 years of ZDV monotherapy. Baseline characteristic s and all RT mutations were analyzed for impact on virologic suppression. E ight of 31 subjects (27%) achieved a virologic response of greater than 0.3 log reduction in plasma HIV RNA after 8 weeks of d4T. Responders were more likely to have lower median baseline viral loads (4.2 vs. 4.7; p = .01) an d a trend toward fewer ZDV-associated mutations (median: I vs. 2; p = .09). No subject with greater than one ZDV mutation had a virologic response to d4T. Seven of the 8 responders had only a K70R mutation at baseline. We con clude that in patients with prior ZDV treatment. those with only one ZDV mu tation, particularly at position 70, can still get reasonable virologic act ivity from d4T. Those with more mutations are not likely to have much benef it.