title: The safety and efficacy of zidovudine (AZT) in the treatment of subjects with mildly symptomatic human immunodeficiency virus type 1 (HIV) infection. A double-blind, placebo-controlled trial. The AIDS Clinical Trials Group.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of zidovudine early in the treatment of human immunodeficiency virus type 1 (HIV) infection.
  
  
  METHODS
  A double-blind, randomized, placebo-controlled trial with subject stratification by pretreatment CD4 T lymphocyte counts.
  
  
  METHODS
  Multicenter trial at AIDS Clinical Trial units.
  
  
  METHODS
  Seven hundred eleven subjects with mildly symptomatic HIV infection.
  
  
  METHODS
  Three hundred fifty-one subjects were assigned to placebo and 360 to zidovudine, 200 mg orally every 4 hours. The median duration of follow-up was 11 months.
  
  
  RESULTS
  Fifty-one subjects developed the acquired immunodeficiency syndrome (AIDS), advanced AIDS-related complex, or death as a first critical event. For the stratum of subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 before treatment, 34 events occurred in placebo recipients and 12 in zidovudine recipients (P = 0.0002; relative risk [RR] estimate, 3.23 [95% CI, 1.67 to 6.24]). For the stratum of subjects with 500 to 799 CD4 T lymphocytes/mm3 before treatment, 2 events occurred in placebo recipients and 3 in zidovudine recipients. Candidiasis at study entry independently increased the risk for having an event (P = 0.005; RR estimate, 2.3 [95% CI, 1.29 to 4.12]); HIV antigenemia at study entry also increased this risk (P = 0.01; RR estimate, 2.1 [95% CI, 1.2 to 3.8]). Significant differences between the treatment groups in CD4 T-lymphocyte counts occurred in subjects with more than 200 but less than 500 CD4 T lymphocytes/mm3 after 4 weeks of therapy (P = 0.002). Differences persisted through week 52. Less prominent changes occurred in subjects with 500 or more CD4 T lymphocytes/mm3. Serum levels of HIV antigen decreased significantly in zidovudine recipients. Serious anemia and neutropenia occurred in 5% and 4% of zidovudine recipients, respectively, and in 0% and 1% of placebo recipients, respectively.
  
  
  CONCLUSIONS
  Zidovudine delayed progression of HIV disease and produced little toxicity in subjects with mildly symptomatic HIV disease and less than 500 CD4 T lymphocytes/mm3.
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: D D
authors.initials: DD
authors.lastname: Richman
authors.forename: N
authors.initials: N
authors.lastname: Hansen
authors.forename: A C
authors.initials: AC
authors.lastname: Collier
authors.forename: J T
authors.initials: JT
authors.lastname: Carey
authors.forename: M F
authors.initials: MF
authors.lastname: Para
authors.forename: W D
authors.initials: WD
authors.lastname: Hardy
authors.forename: R
authors.initials: R
authors.lastname: Dolin
authors.forename: W G
authors.initials: WG
authors.lastname: Powderly
authors.forename: J D
authors.initials: JD
authors.lastname: Allan
mesh_terms: D000386:AIDS-Related Complex / Q000188:drug therapy / Q000453:epidemiology; D000163:Acquired Immunodeficiency Syndrome / Q000453:epidemiology; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D005260:Female; D015488:HIV Antigens / Q000378:metabolism; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1 / Q000276:immunology; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D015337:Multicenter Studies as Topic; D009894:Opportunistic Infections / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D015488:HIV Antigens; D015215:Zidovudine