Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults: A randomized equivalence trial.
BACKGROUND
Abacavir, a nucleoside analogue, has demonstrated suppression of human immunodeficiency virus (HIV) replication alone and in combination therapy. However, the role of abacavir in a triple nucleoside combination regimen has not been evaluated against a standard protease inhibitor-containing regimen for initial antiretroviral treatment.


OBJECTIVE
To evaluate antiretroviral equivalence and safety of an abacavir-lamivudine-zidovudine regimen compared with an indinavir-lamivudine-zidovudine regimen.


METHODS
A multicenter, phase 3, randomized, double-blind trial with an enrollment period from August 1997 to June 1998, with follow-up through 48 weeks at 73 clinical research units in the United States, Canada, Australia, and Europe.


METHODS
Five hundred sixty-two antiretroviral-naive, HIV-infected adults with a plasma HIV RNA level of at least 10 000 copies/mL and a CD4 cell count of at least 100 x 10(6)/L.


METHODS
Patients were stratified by baseline HIV RNA level and randomly 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 greater than 400 copies/mL were eligible to continue receiving randomized treatment or receive open-label therapy.


METHODS
Virologic suppression, defined as HIV RNA concentration of 400 copies/mL or less at week 48.


RESULTS
The proportion of patients who met the end point of having an HIV RNA 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 treatment difference of -0.6% (95% confidence interval [CI], -9% to 8%). In patients with baseline HIV RNA levels greater than 100 000 copies/mL, the proportion of patients achieving less than 50 copies/mL was greater in the indinavir group than in the abacavir group with 45% (45/100) vs 31% (30/96) and a treatment diference of -14% (95% CI, -27% to 0%). The 2 treatments were comparable with respect to their effects on CD4 cell count. There was no difference between groups in the frequency of treatment-limiting adverse events or laboratory abnormalities. One death in the abacavir group was attributed to hypersensitivity reaction, which occurred following rechallenge with 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.
Klinikum der Johann Wolfgang Goethe-Universität, Zentrum der Inneren Medizin, Infektionsambulanz, Haus 68, Theodor-Stern-Kai 7, D-60596 Frankfurt, Germany. stasz@hivcenter.de
S
S
Staszewski
P
P
Keiser
J
J
Montaner
F
F
Raffi
J
J
Gathe
V
V
Brotas
C
C
Hicks
S M
SM
Hammer
D
D
Cooper
M
M
Johnson
S
S
Tortell
A
A
Cutrell
D
D
Thorborn
R
R
Isaacs
S
S
Hetherington
H
H
Steel
W
W
Spreen
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004352:Drug Resistance, Microbial / Q000235:genetics; D005260:Female; D005838:Genotype; D006678:HIV / Q000201:enzymology / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D054303:HIV Reverse Transcriptase / Q000235:genetics; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage / Q000627:therapeutic use*; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D016019:Survival Analysis; D013810:Therapeutic Equivalency; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use*; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D017320:HIV Protease Inhibitors; D054303:HIV Reverse Transcriptase; D019469:Indinavir; D019259:Lamivudine; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D000099227:Abacavir