Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults - A randomized equivalence trial

Context Abacavir, a nucleoside analogue, has demonstrated suppression of hu man immunodeficiency virus (HIV) replication alone and in combination thera py. However, the role of abacavir in a triple nucleoside combination regime n has not been evaluated against a standard protease inhibitor-containing r egimen for initial antiretroviral treatment. Objective To evaluate antiretroviral equivalence and safety of an abacavir- lamivudine-zidovudine regimen compared with an indinavir-lamivudine-zidovud ine regimen. Design and Setting A multicenter, phase 3, randomized, double-blind trial w ith an enrollment period from August 1997 to June 1998, with follow-up thro ugh 48 weeks at 73 clinical research units in the United States, Canada, Au stralia, and Europe. Patients Five hundred sixty-two antiretroviral-naive, HIV-infected adults w ith a plasma HIV RNA level of at least 10000 copies/mL and a CD4 cell count of at least 100 x 10(6)/L. Interventions Patients were stratified by baseline HIV RNA level and random ly assigned to receive a combination tablet containing 150 mg of lamivudine and 300 mg of zidovudine twice daily plus either 300 mg of abacavir twice daily and indinavir placebo or 800 mg of indinavir every 8 hours daily plus abacavir placebo. After 16 weeks, patients with confirmed HIV RNA levels g reater than 400 copies/mL were eligible to continue receiving randomized tr eatment or receive open-label therapy. Main Outcome Measure Virologic suppression, defined as HIV RNA concentratio n of 400 copies/mL or less at week 48. Results The proportion of patients who met the end point of having an HIV R NA level of 400 copies/mL or less at week 48 was equivalent in the abacavir group (51% [133/262]) and in the indinavir group (51% [136/265]) with a tr eatment difference of -0.6% (95% confidence interval [CI], -9% to 8%). In p atients with baseline HIV RNA levels greater than 100 000 copies/mL, the pr oportion of patients achieving less than 50 copies/mL was greater in the in dinavir group than in the abacavir group with 45% (45/100) vs 31% (30/96) a nd a treatment difference of -14% (95% CI, -27% to 0%). The 2 treatments we re comparable with respect to their effects on CD4 cell count. There was no difference between groups in the frequency of treatment-limiting adverse e vents or laboratory abnormalities. One death in the abacavir group was attr ibuted to hypersensitivity reaction, which occurred following rechallenge w ith abacavir, approximately 3 weeks after initiating study treatment. Conclusions In this study of antiretroviral-naive HIV-infected adults, the triple nucleoside regimen of abacavir-lamivudine-zidovudine was equivalent to the regimen of indinavir-lamivudine-zidovudine in achieving a plasma HIV RNA level of less than 400 copies/mL at 48 weeks.