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

JAMA. 1998 Jul 1;280(1):35-41. doi: 10.1001/jama.280.1.35.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Resistance, Microbial
  • Drug Therapy, Combination
  • Follow-Up Studies
  • HIV Infections / drug therapy*
  • HIV-1* / drug effects
  • HIV-1* / genetics
  • Humans
  • Indinavir / administration & dosage
  • Indinavir / therapeutic use
  • Lamivudine / administration & dosage
  • Lamivudine / therapeutic use
  • Viral Load
  • Zidovudine / administration & dosage
  • Zidovudine / therapeutic use


  • Anti-HIV Agents
  • Lamivudine
  • Zidovudine
  • Indinavir