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Session 77 Poster Session Resistance Testing in Drug Selection Session Time: 4:30-6:30 pm Room 4E-F

591-T. Baseline Phenotypic Susceptibility and Virologic Failure over 144 Weeks among Nucleoside RT Inhibitor Experienced Subjects in ACTG 364 D. Katzenstein*1, R. J. Bosch2, N. Wang2, N. S. Hellmann3, L. Bacheler4, and M. Albrecht5 for the ACTG 364 Study Team 1Stanford Univ, CA; 2Harvard Sch. Publ. Hlth., Boston, MA; 3ViroLogic Inc., South San Francisco, CA; 4Bristol-Myers Squibb, Wilmington, DE; and 5Beth Israel Deaconess Med. Ctr., Boston, MA Background: Phenotypic susceptibility scores (PSS) incorporating treatment regimen and drug resistance may identify patients at risk for virologic failure (VF). PSS was assessed over 144 weeks for virologic outcome in 131 highly nucleoside-experienced subjects from ACTG 364 assigned 2 nucleosides + NFV (46), EFV (45), or both (40). Methods: Phenotypic susceptibility was analyzed from plasma samples using a recombinant assay (ViroLogic). Dichotomous and continuous PSS were based on drug treatment and susceptibility (fold-change) of the baseline isolate. Time to confirmed VF (2 consecutive HIV RNA levels > 2,000 copies/mL, week > 16) on initial study treatment was assessed by Cox proportional hazards regression, adjusting for baseline log10 HIV RNA. Phenotypic sensitivity was defined as <1.5-fold increase in IC50 relative to control for ddI and d4T and <2.5-fold for 3TC, EFV, NFV. Hypersusceptibility to EFV (HS), a fold-change of < 0.4, was considered as a dichotomous, independent variable. Results: Higher PSS was significantly associated with lower risk for VF as a continuous (p=0.001) or dichotomous (p=0.004) score, adjusting for baseline HIV RNA. Number of new 364 drugs (p<0.001), but not baseline CD4, was also significantly associated with outcome. Among the 91 subjects on triple-therapy arms (NFV or EFV + 2 NRTIs), there was a trend of increased PSS and decreased risk of VF (p=0.096). In the 2 EFV-containing arms showed there was a significant association with reduced risk of VF with lower baseline HIV RNA (p=0.032), higher continuous PSS (p=0.003), and EFV HS (p=0.042). Conclusions: Lower baseline viral load, a higher PSS score (receipt of more active drugs), and EFV HS were independently associated with a lower risk for VF. The PSS based on lower cut-off values for ddI and d4T was significantly associated with virologic outcome among highly nucleoside-experienced subjects over 144 weeks. Additional studies are needed to validate the lower biological d4T and ddI cut-offs and the role of EFV HS in experienced patients.

©2002 9th Conference on Retroviruses and Opportunistic Infections