title: Phase I studies of 2',3'-dideoxycytidine in severe human immunodeficiency virus infection as a single agent and alternating with zidovudine (AZT).
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 less than 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 less than 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.
mesh_terms: D000386:AIDS-Related Complex / Q000188:drug therapy*; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000328:Adult; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D006678:HIV / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D013936:Thymidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016047:Zalcitabine; D015215:Zidovudine
chemical_list: D003841:Deoxycytidine; D015215:Zidovudine; D016047:Zalcitabine; D013936:Thymidine