PHASE I STUDIES OF 2',3'-DIDEOXYCYTIDINE IN SEVERE HUMAN IMMUNODEFICIENCY VIRUS INFECTION AS A SINGLE AGENT AND ALTERNATING WITH ZIDOVUDINE (AZT)

Robert Yarchoan, RoseV Thomas, Jean Pierre Allain, Nanette Mcatee, Richard Dubinsky, Hiroaki Mitsuya, ThomasJ Lawley, Bijan Safai, CharlesE Myers, CarloFederico Perno, RaymondW Klecker, RobertJ Wills, Margaret A Fischl, M. Carol Mcneely, JamesM Pluda, Michael Leuther, JerryM Collins, Samuel Broder

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Abstract

Five dose regimens of 2',3'-dideoxycytidine (ddC) were administered, intravenously for 2 weeks then orally for 4 or more weeks, to 20 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). ddC was well absorbed from the gut and crossed the blood-brain barrier. 10 of the 15 patients who received 0·03-0·09 mg/kg every 4 h had increases in their absolute number of T4+ T cells at week 2 (p < 0·05), though in many these rises were not sustained. 11 of 13 evaluable patients had a fall in their serum human immunodeficiency virus (HIV) p24 antigen by week 2 of therapy (p < 0·01); in 4 patients the p24 antigen subsequently rose to baseline while in others the decline was sustained. Dose-related toxic effects included cutaneous eruptions, fever, mouth sores, thrombocytopenia, and neutropenia. A reversible painful peripheral neuropathy developed in 10 patients after 6-14 weeks' treatment. These results suggest that ddC has activity against HIV in vivo and has a different toxicity profile from that of zidovudine (AZT). 6 patients with AIDS or ARC were given an alternating regimen of oral AZT (200 mg every 4 h for 7 days) and oral ddC (0·03 mg/kg every 4 h for 7 days). The regimen was well tolerated, and the 5 patients who completed 9 or more weeks of treatment had sustained rises in their T4+ T cells and/or falls in p24 antigen.

Original languageEnglish
Pages (from-to)76-81
Number of pages6
JournalThe Lancet
Volume331
Issue number8577
DOIs
StatePublished - Jan 16 1988

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Zalcitabine
Zidovudine
Virus Diseases
HIV
CD4-Positive T-Lymphocytes
Acquired Immunodeficiency Syndrome
Antigens
T-Lymphocytes
AIDS-Related Complex
Poisons
Peripheral Nervous System Diseases
Neutropenia
Blood-Brain Barrier
Thrombocytopenia
Mouth
Fever
Therapeutics
Skin

ASJC Scopus subject areas

  • Medicine(all)

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PHASE I STUDIES OF 2',3'-DIDEOXYCYTIDINE IN SEVERE HUMAN IMMUNODEFICIENCY VIRUS INFECTION AS A SINGLE AGENT AND ALTERNATING WITH ZIDOVUDINE (AZT). / Yarchoan, Robert; Thomas, RoseV; Allain, Jean Pierre; Mcatee, Nanette; Dubinsky, Richard; Mitsuya, Hiroaki; Lawley, ThomasJ; Safai, Bijan; Myers, CharlesE; Perno, CarloFederico; Klecker, RaymondW; Wills, RobertJ; Fischl, Margaret A; Mcneely, M. Carol; Pluda, JamesM; Leuther, Michael; Collins, JerryM; Broder, Samuel.

In: The Lancet, Vol. 331, No. 8577, 16.01.1988, p. 76-81.

Research output: Contribution to journalArticle

Yarchoan, R, Thomas, R, Allain, JP, Mcatee, N, Dubinsky, R, Mitsuya, H, Lawley, T, Safai, B, Myers, C, Perno, C, Klecker, R, Wills, R, Fischl, MA, Mcneely, MC, Pluda, J, Leuther, M, Collins, J & Broder, S 1988, 'PHASE I STUDIES OF 2',3'-DIDEOXYCYTIDINE IN SEVERE HUMAN IMMUNODEFICIENCY VIRUS INFECTION AS A SINGLE AGENT AND ALTERNATING WITH ZIDOVUDINE (AZT)', The Lancet, vol. 331, no. 8577, pp. 76-81. https://doi.org/10.1016/S0140-6736(88)90283-8
Yarchoan, Robert ; Thomas, RoseV ; Allain, Jean Pierre ; Mcatee, Nanette ; Dubinsky, Richard ; Mitsuya, Hiroaki ; Lawley, ThomasJ ; Safai, Bijan ; Myers, CharlesE ; Perno, CarloFederico ; Klecker, RaymondW ; Wills, RobertJ ; Fischl, Margaret A ; Mcneely, M. Carol ; Pluda, JamesM ; Leuther, Michael ; Collins, JerryM ; Broder, Samuel. / PHASE I STUDIES OF 2',3'-DIDEOXYCYTIDINE IN SEVERE HUMAN IMMUNODEFICIENCY VIRUS INFECTION AS A SINGLE AGENT AND ALTERNATING WITH ZIDOVUDINE (AZT). In: The Lancet. 1988 ; Vol. 331, No. 8577. pp. 76-81.
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abstract = "Five dose regimens of 2',3'-dideoxycytidine (ddC) were administered, intravenously for 2 weeks then orally for 4 or more weeks, to 20 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). ddC was well absorbed from the gut and crossed the blood-brain barrier. 10 of the 15 patients who received 0·03-0·09 mg/kg every 4 h had increases in their absolute number of T4+ T cells at week 2 (p < 0·05), though in many these rises were not sustained. 11 of 13 evaluable patients had a fall in their serum human immunodeficiency virus (HIV) p24 antigen by week 2 of therapy (p < 0·01); in 4 patients the p24 antigen subsequently rose to baseline while in others the decline was sustained. Dose-related toxic effects included cutaneous eruptions, fever, mouth sores, thrombocytopenia, and neutropenia. A reversible painful peripheral neuropathy developed in 10 patients after 6-14 weeks' treatment. These results suggest that ddC has activity against HIV in vivo and has a different toxicity profile from that of zidovudine (AZT). 6 patients with AIDS or ARC were given an alternating regimen of oral AZT (200 mg every 4 h for 7 days) and oral ddC (0·03 mg/kg every 4 h for 7 days). The regimen was well tolerated, and the 5 patients who completed 9 or more weeks of treatment had sustained rises in their T4+ T cells and/or falls in p24 antigen.",
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AU - Thomas, RoseV

AU - Allain, Jean Pierre

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AU - Dubinsky, Richard

AU - Mitsuya, Hiroaki

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AU - Safai, Bijan

AU - Myers, CharlesE

AU - Perno, CarloFederico

AU - Klecker, RaymondW

AU - Wills, RobertJ

AU - Fischl, Margaret A

AU - Mcneely, M. Carol

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