title: 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. AIDS Clinical Trial Group 193A Study Team.
abstract: 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.
  
  
  METHODS
  This was a multicenter randomized, double-blind, placebo-controlled study.
  
  
  METHODS
  The study was conducted among 42 adult AIDS Clinical Trials Group sites and 7 National Hemophilia Foundation centers.
  
  
  METHODS
  1313 HIV-infected patients with CD4 counts < or = 50 cells/mm3 participated in this study, which was conducted from June 1993 to June 1996.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
authors.affiliation: University of Minnesota, Minneapolis, USA. henry02@karloff.fstrf.org
authors.forename: K
authors.initials: K
authors.lastname: Henry
authors.forename: A
authors.initials: A
authors.lastname: Erice
authors.forename: C
authors.initials: C
authors.lastname: Tierney
authors.forename: H H
authors.initials: HH
authors.lastname: Balfour
authors.forename: M A
authors.initials: MA
authors.lastname: Fischl
authors.forename: A
authors.initials: A
authors.lastname: Kmack
authors.forename: S H
authors.initials: SH
authors.lastname: Liou
authors.forename: A
authors.initials: A
authors.lastname: Kenton
authors.forename: M S
authors.initials: MS
authors.lastname: Hirsch
authors.forename: J
authors.initials: J
authors.lastname: Phair
authors.forename: A
authors.initials: A
authors.lastname: Martinez
authors.forename: J O
authors.initials: JO
authors.lastname: Kahn
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000008:administration & dosage / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006678:HIV / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000627:therapeutic use*; D010919:Placebos; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015996:Survival Rate; D013997:Time Factors; D016047:Zalcitabine / Q000008:administration & dosage / Q000627:therapeutic use*; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D010919:Placebos; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D016047:Zalcitabine; D019829:Nevirapine; D016049:Didanosine