Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults

A randomized equivalence trial

Schlomo Staszewski, Philip Keiser, Julio Montaner, Francois Raffi, Joe Gathe, Vitor Brotas, Charles Hicks, Scott M. Hammer, David Cooper, Margaret Johnson, Stephanie Tortell, Amy Cutrell, Daren Thorborn, Robin Isaacs, Seth Hetherington, Helen Steel, William Spreen

Research output: Contribution to journalArticle

274 Citations (Scopus)

Abstract

Context: 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. Design and Setting: 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. Patients: Five hundred sixty-two antiretroviral-naive, HIV-infected adults with a plasma HIV RNA level of at least 10000 copies/mL and a CD4 cell count of at least 100 × 106/L. Interventions: 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. Main Outcome Measure: 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 100000 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.

Original languageEnglish (US)
Pages (from-to)1155-1163
Number of pages9
JournalJournal of the American Medical Association
Volume285
Issue number9
StatePublished - Mar 7 2001
Externally publishedYes

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Indinavir
Lamivudine
Zidovudine
HIV
RNA
Nucleosides
Therapeutics
CD4 Lymphocyte Count
Placebos
lamivudine drug combination abacavir
Confidence Intervals
abacavir
Virus Replication
Protease Inhibitors
Tablets
Canada
Hypersensitivity
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults : A randomized equivalence trial. / Staszewski, Schlomo; Keiser, Philip; Montaner, Julio; Raffi, Francois; Gathe, Joe; Brotas, Vitor; Hicks, Charles; Hammer, Scott M.; Cooper, David; Johnson, Margaret; Tortell, Stephanie; Cutrell, Amy; Thorborn, Daren; Isaacs, Robin; Hetherington, Seth; Steel, Helen; Spreen, William.

In: Journal of the American Medical Association, Vol. 285, No. 9, 07.03.2001, p. 1155-1163.

Research output: Contribution to journalArticle

Staszewski, S, Keiser, P, Montaner, J, Raffi, F, Gathe, J, Brotas, V, Hicks, C, Hammer, SM, Cooper, D, Johnson, M, Tortell, S, Cutrell, A, Thorborn, D, Isaacs, R, Hetherington, S, Steel, H & Spreen, W 2001, 'Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults: A randomized equivalence trial', Journal of the American Medical Association, vol. 285, no. 9, pp. 1155-1163.
Staszewski, Schlomo ; Keiser, Philip ; Montaner, Julio ; Raffi, Francois ; Gathe, Joe ; Brotas, Vitor ; Hicks, Charles ; Hammer, Scott M. ; Cooper, David ; Johnson, Margaret ; Tortell, Stephanie ; Cutrell, Amy ; Thorborn, Daren ; Isaacs, Robin ; Hetherington, Seth ; Steel, Helen ; Spreen, William. / Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults : A randomized equivalence trial. In: Journal of the American Medical Association. 2001 ; Vol. 285, No. 9. pp. 1155-1163.
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author = "Schlomo Staszewski and Philip Keiser and Julio Montaner and Francois Raffi and Joe Gathe and Vitor Brotas and Charles Hicks and Hammer, {Scott M.} and David Cooper and Margaret Johnson and Stephanie Tortell and Amy Cutrell and Daren Thorborn and Robin Isaacs and Seth Hetherington and Helen Steel and William Spreen",
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TY - JOUR

T1 - Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults

T2 - A randomized equivalence trial

AU - Staszewski, Schlomo

AU - Keiser, Philip

AU - Montaner, Julio

AU - Raffi, Francois

AU - Gathe, Joe

AU - Brotas, Vitor

AU - Hicks, Charles

AU - Hammer, Scott M.

AU - Cooper, David

AU - Johnson, Margaret

AU - Tortell, Stephanie

AU - Cutrell, Amy

AU - Thorborn, Daren

AU - Isaacs, Robin

AU - Hetherington, Seth

AU - Steel, Helen

AU - Spreen, William

PY - 2001/3/7

Y1 - 2001/3/7

N2 - Context: 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. Design and Setting: 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. Patients: Five hundred sixty-two antiretroviral-naive, HIV-infected adults with a plasma HIV RNA level of at least 10000 copies/mL and a CD4 cell count of at least 100 × 106/L. Interventions: 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. Main Outcome Measure: 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 100000 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.

AB - Context: 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. Design and Setting: 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. Patients: Five hundred sixty-two antiretroviral-naive, HIV-infected adults with a plasma HIV RNA level of at least 10000 copies/mL and a CD4 cell count of at least 100 × 106/L. Interventions: 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. Main Outcome Measure: 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 100000 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.

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