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, MargaretA Fischl, M. Carol Mcneely, JamesM Pluda, Michael Leuther, JerryM Collins, Samuel Broder

Research output: Contribution to journalArticlepeer-review

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
JournalLancet
Volume331
Issue number8577
DOIs
Publication statusPublished - Jan 16 1988

ASJC Scopus subject areas

  • Medicine(all)

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