Continued lamivudine versus delavirdine in combination with indinavir and zidovudine or stavudine in lamivudine-experienced patients: results of Adult AIDS Clinical Trials Group protocol 370

AIDS. 2000 Jul 28;14(11):1553-61. doi: 10.1097/00002030-200007280-00011.

Abstract

Objective: To compare the virologic activity of continued lamivudine (3TC) versus a switch to delavirdine (DLV) when initiating protease inhibitor therapy in nucleoside-experienced patients.

Design: Randomized, open-label, multi-center study.

Setting: Adult AIDS clinical trials units.

Patients: Protease and non-nucleoside reverse transcriptase inhibitor-naive patients who had received 3TC plus zidovudine (ZDV), stavudine (d4T), or didanosine (ddl) for at least 24 weeks.

Interventions: Patients with plasma HIV-1 RNA levels > 500 copies/ml who previously received d4T + 3TC or ddI + 3TC were randomized to ZDV + 3TC + indinavir (IDV) or ZDV + DLV + IDV.

Main outcome measures: Primary endpoints were the proportion of patients with plasma HIV-1 RNA levels < or = 200 copies/ml at 24 weeks, and occurrence of serious adverse events. The proportion of patients with plasma HIV-1 RNA levels < or = 200 copies/ml at week 48 was a secondary endpoint.

Results: At week 24, 58% of subjects in the ZDV + 3TC + IDV arm and 73% in the ZDV + DLV + IDV arm had plasma HIV-1 RNA levels < or = 200 copies/ml (P = 0.29). At week 48, plasma HIV-1 RNA levels were < or = 200 copies/ml in 48% and 83%, respectively (P = 0.007). Rash and hyperbilirubinemia occurred more frequently in the DLV arm than in the 3TC arm. Steady-state plasma IDV levels were higher among patients in the DLV arm as compared with the 3TC arm.

Conclusions: Substituting DLV for 3TC when adding IDV improved virologic outcome in nucleoside-experienced patients. This result might be explained, in part, by the positive effect of DLV on IDV pharmacokinetics.

Publication types

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

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy*
  • Acquired Immunodeficiency Syndrome / immunology
  • Acquired Immunodeficiency Syndrome / virology
  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • Delavirdine / therapeutic use*
  • Female
  • HIV Protease Inhibitors / blood
  • HIV Protease Inhibitors / therapeutic use*
  • Humans
  • Indinavir / blood
  • Indinavir / therapeutic use*
  • Lamivudine / therapeutic use*
  • Male
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Stavudine / therapeutic use*
  • Time Factors
  • Viral Load
  • Zidovudine / therapeutic use*

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Reverse Transcriptase Inhibitors
  • Lamivudine
  • Zidovudine
  • Indinavir
  • Stavudine
  • Delavirdine