Human immunodeficiency virus-infected persons with mutations conferring resistance to zidovudine show reduced virologic responses to hydroxyurea and stavudine-lamivudine

The baseline predictors of poor virologic response (<0.5 log decrease in pl asma virus load) were examined in two 1996 pilot trials of combination nucl eoside-analogue therapy. One trial examined the addition of hydroxyurea to didanosine therapy; the other examined stavudine-lamivudine in combination. In both, predictors of virologic response included the presence of mutatio ns associated with zidovudine resistance. For hydroxyurea, the odds ratio ( OR) of failure to achieve a short-term (4 weeks) virologic response in a bi variate logistic regression model was 30.8 (95% confidence interval [CI], 1 .75-543; P=.02) for use of lower dose hydroxyurea (500 mg/day) and 14.7 (95 % CI, 1.1-200; P =.04) for the presence of a zidovudine-related mutation. F or the stavudine-lamivudine study, the OR of failure to achieve a virologic response at 4 weeks in a multivariate logistic regression model was 23 (95 % CI, 2.7-199; P =.004) for the presence of a mutation at codon 215.