Simultaneous vs sequential initiation of therapy with indinavir, zidovudine, and lamivudine for HIV-1 infection: 100-week follow-up. Academic Article uri icon

Overview

abstract

  • CONTEXT: Combination antiretroviral therapy can markedly suppress human immunodeficiency virus (HIV) replication but the duration of HIV suppression varies among patients. OBJECTIVE: To compare the antiretroviral effect of a 3-drug regimen started simultaneously or sequentially in patients with HIV infection. DESIGN: A multicenter, randomized, double-blind study, modified after at least 24 weeks of blinded therapy to provide open-label 3-drug therapy with follow-up through 100 weeks. SETTING: Four clinical research units PATIENTS: Ninety-seven patients with HIV infection who had taken zidovudine for at least 6 months with serum HIV RNA level of at least 20000 copies/mL and CD4 cell count of 0.05 to 0.40 x 10(9)/L. INTERVENTIONS: Patients were initially randomized to receive 1 of 3 antiretroviral regimens: indinavir, 800 mg every 8 hours; zidovudine, 200 mg every 8 hours and lamivudine, 150 mg every 12 hours; or all 3 drugs. After at least 24 weeks of blinded therapy, all patients received open-label 3-drug therapy. MAIN OUTCOME MEASURES: Antiretroviral activity was assessed by changes in HIV RNA level and CD4 cell count from baseline. Data through 100 weeks were summarized. RESULTS: Simultaneous initiation of indinavir, zidovudine, and lamivudine suppressed HIV RNA in 78% (25/32) of contributing patients to less than 500 copies/mL and increased CD4 cell count to a median of 0.209 x 10(9)/L above baseline at 100 weeks. When these 3 drugs were initiated sequentially, only 30% to 45% of contributing patients (10 of 33 in the zidovudine-lamivudine group and 13 of 29 in the indinavir group, respectively) had a sustained reduction in HIV RNA to less than 500 copies/mL, and median CD4 cell count increased to 0.101 to 0.163 x 10(9)/L above baseline at 100 weeks. CONCLUSIONS: A 3-drug combination of indinavir, zidovudine, and lamivudine started simultaneously has durable antiretroviral activity for at least 2 years. Sequential initiation of the same 3 drugs is much less effective.

authors

  • Gulick, Roy M
  • Mellors, J W
  • Havlir, Diane
  • Eron, J J
  • Gonzalez, Charles
  • McMahon, Deborah
  • Jonas, Leslie
  • Meibohm, Anne
  • Holder, Daniel
  • Schleif, W A
  • Condra, J H
  • Emini, E A
  • Isaacs, Robin
  • Chodakewitz, J A
  • Richman, D D

publication date

  • July 1, 1998

Research

keywords

  • Anti-HIV Agents
  • HIV Infections
  • HIV-1

Identity

Scopus Document Identifier

  • 0032122438

Digital Object Identifier (DOI)

  • 10.1001/jama.280.1.35

PubMed ID

  • 9660361

Additional Document Info

volume

  • 280

issue

  • 1