title: Combination and monotherapy with zidovudine and zalcitabine in patients with advanced HIV disease. The NIAID AIDS Clinical Trials Group.
abstract: OBJECTIVE
  To compare the safety and efficacy of continuing zidovudine therapy with that of zalcitabine alone or zalcitabine and zidovudine used together.
  
  
  METHODS
  A randomized, double-blind, controlled trial.
  
  
  METHODS
  AIDS Clinical Trials units and National Hemophilia Foundation sites.
  
  
  METHODS
  1001 patients with symptomatic human immunodeficiency (HIV) disease and 300 or fewer CD4 cells/mm3 or asymptomatic HIV disease and 200 or fewer CD4 cells/mm3 who had tolerated zidovudine therapy for 6 months or more.
  
  
  METHODS
  Patients were randomly assigned to receive zidovudine, 600 mg/d; zalcitabine, 2.25 mg/d; or zidovudine, 600 mg/d, and zalcitabine, 2.25 mg/d.
  
  
  METHODS
  The primary end point was time to disease progression or death.
  
  
  RESULTS
  The median follow-up time was 17.7 months. The estimated 12-month event-free rates were 70%, 67%, and 73%, respectively, for the zidovudine, zalcitabine, and combination groups (P = 0.26). A trend analysis showed significantly lower progression rates for combination therapy compared with zidovudine therapy as the pretreatment CD4 cell count increased (P = 0.027). For patients with 150 or more CD4 cells/mm3, those receiving combination therapy were less likely to have disease progression or to die than were those receiving zidovudine (relative risk, 0.51; 95% CI, 0.28 to 0.93; P = 0.029). We observed no difference between the zalcitabine and zidovudine groups (relative risk, 0.74; CI, 0.40 to 1.36; P = 0.33). For patients with 50 to 150 CD4 cells/mm3 or fewer than 50 CD4 cells/mm3, we found no differences among the treatment groups (P = 0.69 and P = 0.57, respectively). Severe toxic effects occurred less frequently among patients with 150 or more CD4 cells/mm3.
  
  
  CONCLUSIONS
  We found no overall benefits of zalcitabine used alone or with zidovudine. However, a trend analysis suggested a better outcome for combination therapy compared with zidovudine as the pretreatment CD4 cell count increased.
authors.affiliation: University of Miami School of Medicine, Department of Medicine, FL 33101.
authors.forename: M A
authors.initials: MA
authors.lastname: Fischl
authors.forename: K
authors.initials: K
authors.lastname: Stanley
authors.forename: A C
authors.initials: AC
authors.lastname: Collier
authors.forename: J M
authors.initials: JM
authors.lastname: Arduino
authors.forename: D S
authors.initials: DS
authors.lastname: Stein
authors.forename: J E
authors.initials: JE
authors.lastname: Feinberg
authors.forename: J D
authors.initials: JD
authors.lastname: Allan
authors.forename: J C
authors.initials: JC
authors.lastname: Goldsmith
authors.forename: W G
authors.initials: WG
authors.lastname: Powderly
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D000328:Adult; D015496:CD4-Positive T-Lymphocytes; D003131:Combined Modality Therapy; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D016655:HIV Core Protein p24 / Q000097:blood; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D016047:Zalcitabine / Q000009:adverse effects / Q000627:therapeutic use*; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D016655:HIV Core Protein p24; D015215:Zidovudine; D016047:Zalcitabine