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

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.

[1]  H. Monteil,et al.  HIGH-PERFORMANCE LIQUID CHROMATOGRAPHIC DETERMINATION , 1993 .

[2]  K. Dandekar,et al.  High-performance liquid chromatographic determination of 2',3'-didehydro-3'-deoxythymidine, a new anti-human immunodeficiency virus agent, in human plasma and urine. , 1992, Journal of chromatography.

[3]  S. Kelley,et al.  Treatment of AIDS and AIDS-related complex with 2',3'-dideoxyinosine given once daily. , 1990, Reviews of infectious diseases.

[4]  C. Pettinelli,et al.  2',3'-Dideoxyinosine in patients with AIDS or AIDS-related complex. , 1990, Reviews of infectious diseases.

[5]  S. Broder.  Dideoxycytidine (ddC): a potent antiretroviral agent for human immunodeficiency virus infection. An introduction. , 1990, The American journal of medicine.

[6]  C. Pettinelli,et al.  2',3'-dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS-related complex. A phase I trial. , 1990, The New England journal of medicine.

[7]  J. Ritter,et al.  Once-daily administration of 2',3'-dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS-related complex. Results of a Phase I trial. , 1990, The New England journal of medicine.

[8]  S W Lagakos,et al.  Zidovudine in Asymptomatic Human Immunodeficiency Virus Infection , 1990 .

[9]  A R Moss,et al.  Projections of AIDS morbidity and mortality in San Francisco. , 1990, JAMA.

[10]  L. Klunk,et al.  Disposition in animals of a new anti-HIV agent: 2',3'-didehydro-3'-deoxythymidine. , 1990, Drug metabolism and disposition: the biological fate of chemicals.

[11]  H. Mitsuya,et al.  Clinical pharmacology of 3'-azido-2',3'-dideoxythymidine (zidovudine) and related dideoxynucleosides. , 1989, The New England journal of medicine.

[12]  J. Fillastre,et al.  Zidovudine disposition in patients with severe renal impairment: Influence of hemodialysis , 1989, Clinical pharmacology and therapeutics.

[13]  S. Azen,et al.  Immunophenotyping in a multicenter study: the Transfusion Safety Study experience. , 1989, Clinical immunology and immunopathology.

[14]  H. Ho,et al.  Cellular pharmacology of 2',3'-dideoxy-2',3'-didehydrothymidine, a nucleoside analog active against human immunodeficiency virus , 1989, Antimicrobial Agents and Chemotherapy.

[15]  D. Richman,et al.  HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. , 1989, Science.

[16]  A. Nitenberg,et al.  Reversibility by dipyridamole of thallium-201 myocardial scan defects in patients with sarcoidosis. , 1988, The American journal of medicine.

[17]  E. De Clercq,et al.  The in vitro and in vivo anti-retrovirus activity, and intracellular metabolism of 3'-azido-2',3'-dideoxythymidine and 2',3'-dideoxycytidine are highly dependent on the cell species. , 1988, Biochemical pharmacology.

[18]  R. Schinazi,et al.  Potent and selective in vitro activity of 3'-deoxythymidin-2'-ene (3'-deoxy-2',3'-didehydrothymidine) against human immunodeficiency virus. , 1987, Biochemical pharmacology.

[19]  H. Lane,et al.  Detection of human immunodeficiency virus core protein in plasma by enzyme immunoassay. Association of antigenemia with symptomatic disease and T-helper cell depletion. , 1987, Annals of internal medicine.

[20]  J. Groopman,et al.  Correlation of enzyme-linked immunosorbent assays for serum human immunodeficiency virus antigen and antibodies to recombinant viral proteins with subsequent clinical outcomes in a cohort of asymptomatic homosexual men. , 1987, The American journal of medicine.

[21]  M A Fischl,et al.  The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. , 1987, The New England journal of medicine.

[22]  M A Fischl,et al.  The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. , 1987, The New England journal of medicine.

[23]  E. De Clercq,et al.  The anti-HTLV-III (anti-HIV) and cytotoxic activity of 2',3'-didehydro-2',3'-dideoxyribonucleosides: a comparison with their parental 2',3'-dideoxyribonucleosides. , 1987, Molecular pharmacology.

[24]  T. Matsui,et al.  Inhibitory effect of 2',3'-didehydro-2',3'-dideoxynucleosides on infectivity, cytopathic effects, and replication of human immunodeficiency virus , 1987, Antimicrobial Agents and Chemotherapy.

[25]  J. Sommadossi,et al.  Toxicity of 3'-azido-3'-deoxythymidine and 9-(1,3-dihydroxy-2-propoxymethyl)guanine for normal human hematopoietic progenitor cells in vitro , 1987, Antimicrobial Agents and Chemotherapy.

[26]  J Desmyter,et al.  Both 2',3'-dideoxythymidine and its 2',3'-unsaturated derivative (2',3'-dideoxythymidinene) are potent and selective inhibitors of human immunodeficiency virus replication in vitro. , 1987, Biochemical and biophysical research communications.

[27]  E. Gelmann,et al.  ADMINISTRATION OF 3'-AZIDO-3'-DEOXYTHYMIDINE, AN INHIBITOR OF HTLV-III/LAV REPLICATION, TO PATIENTS WITH AIDS OR AIDS-RELATED COMPLEX , 1986, The Lancet.

[28]  P. Armitage,et al.  Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design. , 1976, British Journal of Cancer.