2',3'-didehydro-3'-deoxythymidine (d4T) in patients with AIDS or AIDS-related complex: a phase I trial

J Infect Dis. 1993 Jan;167(1):21-9. doi: 10.1093/infdis/167.1.21.


2',3'-didehydro-3'-deoxythymidine (d4T) is a pyrimidine analogue and inhibitor of reverse transcriptase with potent in vitro activity against human immunodeficiency virus (HIV). A phase I trial of d4T was conducted in 41 HIV-infected patients, 12 with AIDS and 29 with AIDS-related complex (ARC). Thirty-six patients were evaluatable. The maximum tolerated dose was 2 mg/kg/day. The dose-limiting toxicity was sensory peripheral neuropathy, which occurred in 20 patients (55%). Four patients (11%) developed hepatotoxicity. Five (14%) developed anemia requiring a transfusion but not discontinuation of drug. The mean +/- SE plasma elimination half-life at all dose levels was 1.2 +/- 0.09 h. Increased or stable absolute CD4 counts were seen in most patients. The majority of patients with detectable serum p24 antigen levels had a persistent decrease by 6 months. d4T is a promising drug for patients with AIDS or ARC. This clinical trial is continuing to determine the minimal effective dose.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Controlled Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Complex / drug therapy*
  • Acquired Immunodeficiency Syndrome / drug therapy*
  • Adult
  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / therapeutic use*
  • CD4-Positive T-Lymphocytes / drug effects
  • Dideoxynucleosides / adverse effects
  • Dideoxynucleosides / pharmacokinetics
  • Dideoxynucleosides / therapeutic use*
  • Female
  • HIV Core Protein p24 / analysis
  • Humans
  • Leukocyte Count / drug effects
  • Male
  • Middle Aged
  • Peripheral Nervous System Diseases / chemically induced
  • Stavudine


  • Antiviral Agents
  • Dideoxynucleosides
  • HIV Core Protein p24
  • Stavudine