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Selection of Zidovudine (ZDV) Resistance Mutations by ZDV- or Stavudine (d4T)-based Regimens and Relationship to Subsequent Virologic Response in ACTG 370.

JOHNSON VA, BASSETT RL, KOEL JL, RHODES RA, YOUNG RK, BARRETT H, KURITZKES DR; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 349.

Univ. of Alabama at Birmingham, Birmingham, AL

BACKGROUND: ACTG 370 compared continued lamivudine (3TC) vs a switch to delavirdine (DLV) when adding indinavir (IDV) in nucleoside (NRTI)-experienced subjects. Pts treated with d4T3TC or ddl/3TC were randomized to ZDV/3TC/IDV or ZDV/DLV/IDV; pts treated with ZDV/3TC received d4T/DLV/IDV. Superior virologic response was observed with ZDV/DLV/IDV.METHODS: To determine the prevalence and impact of ZDV resistance (ZDV-R) mutations on Rx response in ACTG 370, RT sequences from baseline (BL) plasma samples were determined by TruGene assay (VGI). Logistic regression models tested associations among virologic success/failure, BL virus load and CD4 cell count, and presence/absence of ZDV-R mutations, controlling for study Rx. Prevalence of >/=1 ZDV-R mutations was similar in ZDV/3TC- (50%) or d4T/3TC-treated pts (38%; p=0.34). 41L was more common in ZDV/3TC- (28%) than in d4T/3TC-treated pts (6%; p=0.007).RESULTS: Presence of >/=1 ZDV-R mutations conferred a reduced risk of virologic failure (plasma HIV RNA >200 c/mL) on triple Rx at wk 48 (OR 0.36; (P=0.048). This association remained significant after controlling for BL CD4 count and virus load (OR 0.23; P=0.010). Similar results were observed with a 50 c/mL endpoint. Conclusion: Salvage regimens in NRTI-experienced subjects can achieve durable plasma viral load responses over 48 weeks despite ZDV-R mutations. Possible mechanisms include medication adherence, antiviral potency, and/or increased NNRTI susceptibility of viruses with ZDV-R mutations.KEYWORDS: Genotyping; HIV-1 drug resistance; Virological response

Publication Types:
  • Meeting Abstracts
Keywords:
  • Acquired Immunodeficiency Syndrome
  • Anti-HIV Agents
  • CD4 Lymphocyte Count
  • Clinical Protocols
  • Delavirdine
  • HIV
  • HIV Infections
  • HIV Protease
  • HIV Protease Inhibitors
  • HIV-1
  • Indinavir
  • Lamivudine
  • Mutation
  • Selection (Genetics)
  • Stavudine
  • Viral Load
  • Zidovudine
  • genetics
  • reverse transcriptase, Human immunodeficiency virus 1
  • virology
Other ID:
  • GWAIDS0010854
UI: 102248352

From Meeting Abstracts




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