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 plasma virus load) were examined in two 1996 pilot trials of combination nucleoside-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 mutations associated with zidovudine resistance. For hydroxyurea, the odds ratio (OR) of failure to achieve a short-term (4 weeks) virologic response in a bivariate 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. For 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.
Montaner
J S
JS
BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, BC, Canada V6Z 1Y6.
Mo
T
T
Raboud
J M
JM
Rae
S
S
Alexander
C S
CS
Zala
C
C
Rouleau
D
D
Harrigan
P R
PR
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use; D016015:Logistic Models; D009154:Mutation; D019384:Nucleic Acid Synthesis Inhibitors / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D018119:Stavudine / Q000627:therapeutic use; D019562:Viral Load; D015215:Zidovudine / Q000494:pharmacology*
D019380:Anti-HIV Agents; D019384:Nucleic Acid Synthesis Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D018119:Stavudine; D006918:Hydroxyurea