title: A randomized controlled trial of a reduced daily dose of zidovudine in patients with the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group.
abstract: BACKGROUND
  The initially tested dose of zidovudine for the treatment of patients with advanced disease caused by the human immunodeficiency virus type 1 (HIV) was 1500 mg. Although this dose is effective, it is associated with substantial toxicity.
  
  
  METHODS
  To evaluate the efficacy and safety of a reduced dose, we conducted a randomized controlled trial in 524 subjects who had had a first episode of Pneumocystis carinii pneumonia. The subjects were assigned to receive zidovudine in either a dose of 250 mg taken orally every four hours (the standard-treatment group, n = 262) or a dose of 200 mg taken orally every four hours for four weeks and thereafter 100 mg taken every four hours (the low-dose group, n = 262).
  
  
  RESULTS
  The median length of follow-up was 25.6 months. At 18 months the estimated survival rates were 52 percent for the standard-treatment group and 63 percent for the low-dose group (P = 0.012 by the log-rank test). At 24 months the estimated survival rates were 27 percent for the standard-treatment group and 34 percent for the low-dose group (P = 0.033). In both groups, 82 percent of the subjects had another opportunistic infection, and the length of time to that infection was similar in the two groups (P = 0.56 by the log-rank test). CD4 T-lymphocyte counts improved transiently in both groups, and serum levels of HIV antigen decreased in the subjects with antigenemia. The hemoglobin level declined to less than 5 mmol per liter (80 g per liter) in 101 subjects in the standard-treatment group and in 77 in the low-dose group (39 vs. 29 percent, P = 0.0009 by the log-rank test). The neutrophil count declined to less than 0.750 x 10(9) per liter in 134 subjects in the standard-treatment group and in 96 in the low-dose group (51 vs. 37 percent, P = 0.0001).
  
  
  CONCLUSIONS
  The reduced daily dose of zidovudine used in this study was at least as effective as the standard dose and was less toxic; however, with the use of a four-week induction period with a high dose followed by low-dose treatment, severe anemia and neutropenia were common complications of treatment with zidovudine.
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: C B
authors.initials: CB
authors.lastname: Parker
authors.forename: C
authors.initials: C
authors.lastname: Pettinelli
authors.forename: M
authors.initials: M
authors.lastname: Wulfsohn
authors.forename: M S
authors.initials: MS
authors.lastname: Hirsch
authors.forename: A C
authors.initials: AC
authors.lastname: Collier
authors.forename: D
authors.initials: D
authors.lastname: Antoniskis
authors.forename: M
authors.initials: M
authors.lastname: Ho
authors.forename: D D
authors.initials: DD
authors.lastname: Richman
authors.forename: E
authors.initials: E
authors.lastname: Fuchs
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000328:Adult; D015496:CD4-Positive T-Lymphocytes; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D015488:HIV Antigens / Q000032:analysis; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D011020:Pneumonia, Pneumocystis / Q000517:prevention & control; D015996:Survival Rate; D015215:Zidovudine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D015488:HIV Antigens; D015215:Zidovudine