ACTG 364: Virologic efficacy of nelfinavir (NFV) and/or efavirenz (EFZ) in combination with new nucleoside analogs in nucleoside experienced subjects.
authors
M. ALBRECHT, D. KATZENSTEIN, R. BOSCH, S. LIOU, S. HAMMER for the ACTG 364 Study Team.
publication
6th Conference on Retroviruses and Opportunistic Infections. 31 Jan-4 Feb, 1999, Chicago, IL. Abstract 489.
ABSTRACT
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.
