• Selection of Zidovudine (ZDV, AZT) Resistance Mutations by ZDV- or Stavudine (d4T)-based Regimens and Relationship to Subsequent Virologic Response in ACTG 370
  Slide Session 2111
  Authored by V. A. Johnson, R. L. Bassett, J. L. Koel, R. A. Rhodes, R. K. Young, H. Barrett, D. R. Kuritzkes

This oral abstract presented information on the impact of ZDV-associated mutations on virologic responses of ZDV and d4T-containing regimens. Baseline sample plasma HIV RNA reverse transcriptase was sequenced from patients enrolling in ACTG 370. Patients who were previously NRTI-experienced from ACTG 306, were enrolled in this study to receive ZDV/3TC/IDV, ZDV/DLV/IDV (having previously received d4T/3TC and ddI/3TC), and d4T/DLV/IDV (having previously received ZDV/3TC). Ninety-five patients were analyzed. The prevalence of >1 ZDV-associated mutation at baseline was 50% (18/36) in patients who had received ZDV/3TC and 38% (12/32) in those patients who had received d4T/3TC. This was found not to be a significant difference. A mutation at codon 41 was found more commonly with ZDV/3TC, but mutations at 70 and 215 were found equally when patients had received ZDV/3TC or d4T/3TC. Patients were followed for 48 weeks after starting the regimens stated above. Patients with >1 ZDV mutation were more likely to have a better viral load response than those patients who did not. The greatest suppression was seen in the delavirdine-containing arms of the study. This finding was consistent irrespective of baseline viral load or CD4 count.

This and other studies continue to report the association and development of ZDV-associated mutations after d4T exposure. It remains controversial whether patients who receive d4T and who have ZDV-associated mutations respond virologically as well as those patients without ZDV mutations. This study showed that patients with ZDV mutations who received d4T/DLV/IDV did have comparable virologic responses to those patients who received ZDV/DLV/IDV. This study also showed that the presence of ZDV mutations resulted in a reduced risk of virologic failure, with more patients achieving an undetectable viral load than those patients without ZDV mutations. Where this finding was related to better adherence, potency of these specific regimens or hypersusceptibility of the NNRTI (delavirdine)-containing regimens in the presence of ZDV mutations is not known.