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Session 61 Poster Session Antiretroviral Chemotherapy in Previously Treated Individuals Session Time: 4:30-6:30 pm Room 4E-F

425-W. ACTG 364: Efficacy of Nelfinavir (NFV) and/or Efavirenz (EFV) in Combination with New NRTIs in Nucleoside Experienced Subjects: Week-144 Results M. A. Albrecht*1, R. J. Bosch2, S. H. Liou2, and D. Katzenstein3 1Beth Israel Deaconess Med. Ctr., Boston, MA; 2 Harvard Sch. of Publ. Hlth., Boston, MA; and 3Stanford Univ. Med. Ctr., CA Background: The optimal alternative therapy for subjects with NRTI experience who develop viral rebound remains uncertain. ACTG 364 examined long-term virologic and immune responses of quadruple vs triple antiretroviral therapy (ART) regimens in exclusively NRTI-treated subjects. This was a randomized, partially-blind trial for ACTG 302/303 highly nucleoside-experienced subjects receiving d4T alone or new NRTI combinations who remained on same treatment at entry into ACTG 364. Methods:196 subjects with screening HIV RNA > 500 copies/mL were randomized to 1 of 3 arms: NFV, EFV placebo, + NRTIs; EFV, NFV placebo, + NRTIs; or NFV, EFV, + NRTIs. Open-label nucleoside therapy was assigned with at least 1 or 2 new NRTIs (ddI+d4T, ddI+3TC, or d4T+3TC). Plasma HIV RNA (Roche Ultrasensitive assay) and CD4 counts were monitored through week 144. Results: 195 subjects were evaluable. The study was blinded through week 48. Baseline (BL) characteristics: median CD4 count and HIV RNA levels were 350 cells/mm3 and 7776 c/mL, respectively. By intent-to-treat analysis, 79 (59%) of 134 subjects with 71% (30/42), 58% (28/48), and 48% (21/44) of subjects in the NFV+EFV, EFV, and NFV arms, respectively, achieved HIV RNA < 50 copies/mL at week 144 (3-way p=0.045). The NFV+EFV arm demonstrated superior viral suppression compared to the NFV arm (pairwise p=0.016) at week 144; the other pairwise comparisons were not significant. In time to virologic failure (confirmed HIV RNA > 200 copies/mL at week 16 or later) analyses, a highly significant difference among the three study arms (p< 0.001) was seen. In pairwise comparisons, the quadruple- and EFV- triple arms required a longer time to reach virologic failure compared to the NFV arm: p<0.001 and p=0.028, respectively; quadruple therapy arm vs EFV arm (p=0.003). At week 144, a median CD4 increase of 171 cells/mm3 from baseline was seen. Conclusions: In nucleoside-experienced subjects with virologic failure, alternative therapy with at least 2 new potent ART drugs in combination with new NRTIs provides a greater likelihood of achieving durable virologic suppression.

©2002 9th Conference on Retroviruses and Opportunistic Infections