A randomized, controlled, double-blind study comparing the survival benefit of four different reverse transcriptase inhibitor therapies (three-drug, two-drug, and alternating drug) for the treatment of advanced AIDS

Keith Henry, Alejo Erice, Camlin Tierney, Henry H. Balfour, Margaret A. Fischl, Anne Kmack, Song Heng Liou, Antoinette Kenton, Martin S. Hirsch, John Phair, Ana Martinez, James O. Kahn

Research output: Contribution to journalArticle

59 Scopus citations


Objective: The primary objective was to compare the effects of dual or triple combinations of HIV-1 reverse transcriptase inhibitors with respect to survival. The time to new HIV disease progression or death, toxicities, the change in CD4 cells, and plasma HIV-1 RNA concentrations in a subset of study subjects were evaluated. Design: This was a multicenter randomized, double- blind, placebo-controlled study. Setting: The study was conducted among 42 adult AIDS Clinical Trials Group sites and 7 National Hemophilia Foundation centers. Patients: 1313 HIV-infected patients with CD4 counts ≤ 50 cells/mm3 participated in this study, which was conducted from June 1993 to June 1996. Intervention: Patients were randomized to one of four daily regimens containing 600 mg of zidovudine: zidovudine alternating monthly with 400 mg didanosine; zidovudine plus 2.25 mg of zalcitabine; zidovudine plus 400 mg of didanosine; or zidovudine plus 400 mg of didanosine plus 400 mg of nevirapine (triple therapy). Main Outcome Measures: The main outcome was survival (i.e., time to death). Results: A significant difference in survival time was found between the four treatment groups, favoring those assigned to triple therapy (p = .02). A significant difference was also found in the delay of disease progression or death among the four treatment arms favoring the group assigned to triple therapy (p = .002). Baseline CD4 cell counts and plasma HIV-1 RNA concentrations as well as changes of CD4 counts at week 8 predicted survival for subjects in the virology substudy. Conclusions: In the pre-protease inhibitor era, a combination of triple reverse transcriptase inhibitors prolonged life and delayed disease progression in AIDS patients with advanced immune suppression.

Original languageEnglish (US)
Pages (from-to)339-349
Number of pages11
JournalJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology
Issue number4
StatePublished - Dec 1 1998



  • AIDS
  • Antiretroviral therapy
  • CD4 lymphocyte count
  • Didanosine
  • HIV-1 RNA
  • Nevirapine
  • Reverse transcriptase inhibitors
  • Survival
  • Zalcitabine
  • Zidovudine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Virology

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