AEGiS-07CROI: Randomized trial of abacavir (ABC) in combination with indinavir (IDV) and efavirenz (EFV) in HIV-infected patients (pts) with nucleoside analog experience (NRTI Exp).

7th Conference on Retroviruses and Opportunistic Infections


San Francisco, CA - January 30 -February 4, 2000



Randomized trial of abacavir (ABC) in combination with indinavir (IDV) and efavirenz (EFV) in HIV-infected patients (pts) with nucleoside analog experience (NRTI Exp).

Conf Retroviruses Opportunistic Infect 2000 Jan 30-Feb 2; 7:175 (abstract no. 529)

Squires K, Hammer S, Degruttola V, Fischl M, Bettendorf D, Demeter L, Morse G; 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-naïve 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. 1prime 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=0.03). 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.

Keywords: AEGIS, Indinavir, Dideoxynucleosides, Oxazines, HIV, Stavudine, Zidovudine, Lamivudine, Anti-HIV Agents, CD4 Lymphocyte Count, Reverse Transcriptase Inhibitors, HIV Protease Inhibitors, HIV Infections, HIV-1, abacavir, efavirenz, Human, AIDSKWDaegis,indinavir,dideoxynucleosides,oxazines,hiv,stavudine,zidovudine,lamivudine,anti-hivagents,cd4lymphocytecount,reversetranscriptaseinhibitors,hivproteaseinhibitors,hivinfections,hiv-1,abacavir,efavirenz,human,aids

2000-01-30
529

Copyright © 2000 - Foundation for Retrovirology and Human Health (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed from National Library of Medicine.