The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial

D. D. Richman, Margaret A Fischl, M. H. Grieco, M. S. Gottlieb, P. A. Volberding, O. L. Laskin, J. M. Leedom, J. E. Groopman, D. Mildvan, M. S. Hirsch

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Abstract

We conducted a double-blind, placebo-controlled trial of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Although significant clinical benefit was documented (N Engl J Med 1987; 317:185-91), serious adverse reactions, particularly bone marrow suppression, were observed. Nausea, myalgia, insomnia, and severe headaches were reported more frequently by recipients of AZT; macrocytosis developed within weeks in most of the AZT group. Anemia with hemoglobin levels below 7.5 g per deciliter developed in 24 percent of AZT recipients and 4 percent of placebo recipients (P < 0.001). Twenty-one percent of AZT recipients and 4 percent of placebo recipients required multiple red-cell transfusions (P < 0.001). Neutropenia (<500 cells per cubic millimeter) occurred in 16 percent of AZT recipients, as compared with 2 percent of placebo recipients (P < 0.001). Subjects who entered the study with low CD4 lymphocyte counts, low serum vitamin B12 levels, anemia, or low neutrophil counts were more likely to have hematologic toxic effects. Concurrent use of acetaminophen was also associated with a higher frequency of hematologic toxicity. Although a subset of patients tolerated AZT for an extended period with few toxic effects, the drug should be administered with caution because of its toxicity and the limited experience with it to date.

Original languageEnglish
Pages (from-to)192-197
Number of pages6
JournalNew England Journal of Medicine
Volume317
Issue number4
StatePublished - Sep 17 1987

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Zidovudine
Acquired Immunodeficiency Syndrome
Placebos
Poisons
Anemia
Therapeutics
Myalgia
Sleep Initiation and Maintenance Disorders
Vitamin B 12
CD4 Lymphocyte Count
Acetaminophen
Neutropenia
Nausea
Headache
Hemoglobins
Neutrophils
Bone Marrow
Serum
Pharmaceutical Preparations
4'-azidothymidine

ASJC Scopus subject areas

  • Medicine(all)

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Richman, D. D., Fischl, M. A., Grieco, M. H., Gottlieb, M. S., Volberding, P. A., Laskin, O. L., ... Hirsch, M. S. (1987). The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. New England Journal of Medicine, 317(4), 192-197.

The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. / Richman, D. D.; Fischl, Margaret A; Grieco, M. H.; Gottlieb, M. S.; Volberding, P. A.; Laskin, O. L.; Leedom, J. M.; Groopman, J. E.; Mildvan, D.; Hirsch, M. S.

In: New England Journal of Medicine, Vol. 317, No. 4, 17.09.1987, p. 192-197.

Research output: Contribution to journalArticle

Richman, DD, Fischl, MA, Grieco, MH, Gottlieb, MS, Volberding, PA, Laskin, OL, Leedom, JM, Groopman, JE, Mildvan, D & Hirsch, MS 1987, 'The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial', New England Journal of Medicine, vol. 317, no. 4, pp. 192-197.
Richman, D. D. ; Fischl, Margaret A ; Grieco, M. H. ; Gottlieb, M. S. ; Volberding, P. A. ; Laskin, O. L. ; Leedom, J. M. ; Groopman, J. E. ; Mildvan, D. ; Hirsch, M. S. / The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. In: New England Journal of Medicine. 1987 ; Vol. 317, No. 4. pp. 192-197.
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