Background: The ideal treatment (Rx) for multiple NRTI exposed individuals is unknown. ACTG 364 was designed to determine if new NRTIs combined with NFV and/or EFZ are effective in suppressing viral load in extensively NRTI-exposed subj.

Design: Randomized, phase II, partially blind trial for subj with extensive but exclusive NRTI exposure in prior ACTG trials (ACTG 175; rollover studies ACTG 302/303) and who remained on same Rx at entry. 196 subj with screening HIV RNA > 500 c/mL were randomized: ARM I: NFV, EFZ placebo, + RTIs*; ARM II: NFV placebo, EFZ, + RTIs*; or ARM III: NFV, EFZ, + RTIs*. [*Open label RTIs assigned with at least 1 or 2 new RTIs (ddI+d4T, 3TC+d4T, or ddI+3TC)]. Plasma HIV RNA (Roche Amplicor assay) and CD4 counts were monitored through wk 48.

Results: 195 subj evaluable; study blinded through wk 48. BL characteristics: mean CD4 count and median BL HIV RNA were 388/mm3 and 7,625 c/mL, respectively. 138/194 subj (71%) with 64%, 69% and 81% subj in the NFV, EFZ, and NFV+EFZ arms, respectively, at wk 16 achieved plasma HIV RNA <500 c/mL (3-way p=0.093). In pairwise comparisons, a higher proportion of subj in the NFV+EFZ arm compared to the NFV arm achieved HIV RNA <500 c/mL at wk 16 (p=0.03). A mean CD4 cell increase of 79/mm3 was seen at wk 16. BL predictors for wk 16 HIV RNA <500 c/mL included: 1 log10 lower BL HIV RNA (Odds ratio [OR]: 4.48; p<0.001) and receipt of 2 vs. 1 new RTIs (OR: 4.27; p<0.001). At wk 48, 138/196 (70%) subj maintain HIV RNA <2000 c/mL and remain on randomized open label therapy. The 3 Rx arms have been well tolerated.

Conclusions: Adding NFV and/or EFZ to a regimen with 1 or 2 new RTIs provided effective suppression in 71% of subj at wk 16. Long term (wks 40-48) CD4 and HIV RNA responses and results by Rx arm to be presented.