7th Conference - Abstract 529

Randomized Trial of Abacavir (ABC) in Combination with Indinavir (IDV) and Efavirenz (EFV) in HIV-Infected Patients (Pts) with Nucleoside Analog Experience (NRTI Exp)

K. SQUIRES*, S. HAMMER, V. DEGRUTTOLA, M. FISCHL, D. BETTENDORF, L. DEMETER, G. MORSE, and the ACTG 368 Study Team. NIAID Sponsored AIDS Clin. Trials Group, Bethesda, MD

Limited data are available to guide optimal therapeutic strategies for NRTI exp pts. ACTG 368, a roll over study of ACTG 320, was factorially designed to compare: 1. ABC vs ABC placebo (plac) and 2. q12 vs standard q8h dosing regimens of IDV and EFV. 283 PI, NNRTI-naive pts with CD4 cell counts (cts) <250/mm3 who received at least 2 months ZDV (d4t) + 3TC were randomized to ABC 300mg BID vs plac; 123 of these pts with CD4 cts >50/mm3 were randomized to IDV 1000mg q8h+EFV 600mg qd+ABC vs IDV 1200 mg q12h +ABC. Pts were stratified by BL CD4 ct (<50 [71] and >50 [212]); analysis was ITT. 1° study endpoint: HIV RNA level >500 copies/mL (c/mL) at 16 wks; subsequent study endpoints: HIV RNA>500c/mL and Rx failure. Overall, mean BL HIV RNA and CD4 ct were 4.3 log10 c/mL and 133/mm3, respectively. For the IDV + EFV dosing comparison, there were fewer failures on the IDV q8h dosing arm at wks 16, 32 and 48 and the pts receiving IDV q12h were switched to IDV q8h+ EFV qd. For the ABC vs plac comparison, 29% (82/283) pts reached the primary study endpoint; 27% ABC vs 31% plac (p=0.51). By wk 32, 126/283 (45%) pts reached study endpoint; 41% ABC vs 48% plac. A significant interaction (p=0.02) between ABC and CD4 strata was seen: 35% ABC vs 51% plac (p=0.03) failures in the >50/mm3 stratum and 62% ABC vs 38% plac in the <50/mm3 stratum. At week 48, 43% ABC and 51% plac pts reached study endpoint (p=0.19). The average changes from baseline in CD4 cts were similar for both major comparisons. The incidence of ABC hypersensitivity reaction was 1.5% and time to onset of Grade 3 or 4 clinical AE's was faster in the ABC-containing arms (p=.03).
In this highly NRTI-experienced patient population, the time to study failure was more prolonged in pts with BL CD4 cts >50 /mm3 receiving ABC in addition to IDV +EFV. Genotypic and phenotypic analyses are ongoing.

Key Words: Abacavir, Clinical Trial, NRTI Experience