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ACTC 364- Nelfinavir (NFV) and/or Efavirenz (EFV) in Combination with New NRTIs in Nucleoside Experienced Subjects (Subj): Week-48 Ultrasensitive (US) HIV RNA Results M. ALBRECHT*, D. KATZENSTEIN, R. BOSCH, S. LIOU, and S. HAMMER.
NIAID Sponsored AIDS Clin. Trials Group, Bethesda, MD Background: Optimal 2nd line treatment (Rx) for multiple NRTI exposed individuals with viral rebound is not yet defined. ACTG 364 evaluated whether new NRTIs combined with NFV and/or EFV would effectively suppress viral load (VL) in extensively NRTI treated subj.
Design: Randomized, phase II, partially <$>blind trial for subj with extensive but exclusive NRTI exposure in prior ACTG (ACTG 175; ACTG 302/303) trials; subj on same Rx at entry. 196 subj with screening VL >500 c/mL were randomized: Arm I (NFV, EFV placebo,+ NRTIs*; Arm II: EFV+NFV placebo+NRTIs*; or Arm III: NFV, EFV,+NRTIs*.{*open label RTIs: 1 or 2 new NRTIs assigned (ddI+d4T, 3TC+d4T, or ddI+3TC)}. Plasma VL (Roche Amplicor assay) and CD4 counts were monitored through wk 48. US HIV RNA (LOQ < 50 c/mL) results were analyzed.
Results: 195 subj evaluable; study blinded through wk 48. BL characteristics: mean CD4 count and median plasma VL were 389/mm3 and 7776 c/mL, respectively. 82/188 (44%) subj across Rx arms; 22%, 44%, and 67% subj in the NFV, EFV, and the NFV+EFV arms, respectively, achieved VL < 50 c/mL at wks 40-48. In pairwise comparisons, the NFV+EFV arm had superior VL suppression compared to the NFV (p=0.001) and EFV (p=0.008) arms; the EFV arm achieved greater VL suppression compared to the NFV arm (p=0.008). After adjusting for randomized Rx, BL predictors for wks 40-48 VL < 50 c/mL included: 1 log10 lower BL RNA (Odds ratio [OR]: 2.30; p < 0.001) and 3TC as new NRTI at study entry (OR: 3.34; p< 0.001). Time to VL >200 c/mL in subj with VL < 50 c/mL at wk 16 was significantly shorter in NFV (p < 0.001) and EFV (p=0.003) arms compared to the NFV+EFV arm.
Conclusions: Dual NFV and EFV, in combination with new NRTIs provides significantly greater and more durable VL suppression compared to triple NFV- or EFV-based regimens in NRTI exposed subj.
Key Words: combination antiviral therapy, efavirenz (sustiva), nelfinavir (viracept)
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