2′,3′-Didehydro-3′-deoxythymidine (d4t) in patients with AIDS or AIDS-related complex: A Phase I Trial

Marcia J. Browne; Kenneth H. Mayer; Stephanie B.D. Chafee; Michael N. Dudley; Marshall R. Posner; Seth M. Steinberg; Kathleen K. Graham; Sandra M. Geletko; Stephen H. Zinner; Sandra L. Denman; Lisa M. Dunkle; Sanjeev Kaul; Colin McLaren; Gail Skowron; Nicola M. Kouttab; Theresa A. Kennedy; Alan B. Weitberg; Gregory A. Curt

doi:10.1093/infdis/167.1.21

2′,3′-Didehydro-3′-deoxythymidine (d4t) in patients with AIDS or AIDS-related complex: A Phase I Trial

Marcia J. Browne, Kenneth H. Mayer, Stephanie B.D. Chafee, Michael N. Dudley, Marshall R. Posner, Seth M. Steinberg, Kathleen K. Graham, Sandra M. Geletko, Stephen H. Zinner, Sandra L. Denman, Lisa M. Dunkle, Sanjeev Kaul, Colin McLaren, Gail Skowron, Nicola M. Kouttab, Theresa A. Kennedy, Alan B. Weitberg, Gregory A. Curt

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Abstract

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 levelswas 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 levelshad 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.

Original language	English
Pages (from-to)	21-29
Number of pages	9
Journal	Journal of Infectious Diseases
Volume	167
Issue number	1
DOIs	https://doi.org/10.1093/infdis/167.1.21
State	Published - Jan 1993
Externally published	Yes

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Browne, M. J., Mayer, K. H., Chafee, S. B. D., Dudley, M. N., Posner, M. R., Steinberg, S. M., Graham, K. K., Geletko, S. M., Zinner, S. H., Denman, S. L., Dunkle, L. M., Kaul, S., McLaren, C., Skowron, G., Kouttab, N. M., Kennedy, T. A., Weitberg, A. B., & Curt, G. A. (1993). 2′,3′-Didehydro-3′-deoxythymidine (d4t) in patients with AIDS or AIDS-related complex: A Phase I Trial. Journal of Infectious Diseases, 167(1), 21-29. https://doi.org/10.1093/infdis/167.1.21

@article{ec44d1c85e6c4f34b4b70fda32ee26f2,

title = "2′,3′-Didehydro-3′-deoxythymidine (d4t) in patients with AIDS or AIDS-related complex: A Phase I Trial",

abstract = "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 levelswas 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 levelshad 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.",

author = "Browne, {Marcia J.} and Mayer, {Kenneth H.} and Chafee, {Stephanie B.D.} and Dudley, {Michael N.} and Posner, {Marshall R.} and Steinberg, {Seth M.} and Graham, {Kathleen K.} and Geletko, {Sandra M.} and Zinner, {Stephen H.} and Denman, {Sandra L.} and Dunkle, {Lisa M.} and Sanjeev Kaul and Colin McLaren and Gail Skowron and Kouttab, {Nicola M.} and Kennedy, {Theresa A.} and Weitberg, {Alan B.} and Curt, {Gregory A.}",

year = "1993",

month = jan,

doi = "10.1093/infdis/167.1.21",

language = "English",

volume = "167",

pages = "21--29",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

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Browne, MJ, Mayer, KH, Chafee, SBD, Dudley, MN, Posner, MR, Steinberg, SM, Graham, KK, Geletko, SM, Zinner, SH, Denman, SL, Dunkle, LM, Kaul, S, McLaren, C, Skowron, G, Kouttab, NM, Kennedy, TA, Weitberg, AB & Curt, GA 1993, '2′,3′-Didehydro-3′-deoxythymidine (d4t) in patients with AIDS or AIDS-related complex: A Phase I Trial', Journal of Infectious Diseases, vol. 167, no. 1, pp. 21-29. https://doi.org/10.1093/infdis/167.1.21

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T1 - 2′,3′-Didehydro-3′-deoxythymidine (d4t) in patients with AIDS or AIDS-related complex

T2 - A Phase I Trial

AU - Browne, Marcia J.

AU - Mayer, Kenneth H.

AU - Chafee, Stephanie B.D.

AU - Dudley, Michael N.

AU - Posner, Marshall R.

AU - Steinberg, Seth M.

AU - Graham, Kathleen K.

AU - Geletko, Sandra M.

AU - Zinner, Stephen H.

AU - Denman, Sandra L.

AU - Dunkle, Lisa M.

AU - Kaul, Sanjeev

AU - McLaren, Colin

AU - Skowron, Gail

AU - Kouttab, Nicola M.

AU - Kennedy, Theresa A.

AU - Weitberg, Alan B.

AU - Curt, Gregory A.

PY - 1993/1

Y1 - 1993/1

N2 - 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 levelswas 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 levelshad 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.

AB - 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 levelswas 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 levelshad 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.

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AN - SCOPUS:0027398462

SN - 0022-1899

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JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 1

ER -

2′,3′-Didehydro-3′-deoxythymidine (d4t) in patients with AIDS or AIDS-related complex: A Phase I Trial

Abstract

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