title: Dideoxycytidine alone and in an alternating schedule with zidovudine in children with symptomatic human immunodeficiency virus infection.
abstract: OBJECTIVE
  To determine whether a short course of 2',3'-dideoxycytidine (ddC) could provide safe antiretroviral activity in children with symptomatic human immunodeficiency virus infection and whether it could be used with azidothymidine (AZT, zidovudine). The goal was to maintain uninterrupted antiretroviral therapy while sparing AZT-related myelosuppression and ddC-related neuropathy.
  
  
  METHODS
  In a pilot study, we evaluated four dosage levels of ddC--0.015, 0.02, 0.03, and 0.04 mg/kg, given orally every 6 hours--in 15 children between 6 months and 13 years of age with Centers for Disease Control P2 (i.e., symptomatic) human immunodeficiency virus infection. Thirteen patients had not had any prior antiretroviral therapy; two patients had received and benefited from AZT, but dose-limiting neutropenia had developed. At each dosage level, ddC was given for 8 consecutive weeks and then stopped. After a 30-day rest, a schedule of ddC for 1 week was followed by 3 weeks of AZT therapy (180 mg/m2 every 6 hours); this alternating schedule was repeated for as long as tolerated. Age-appropriate psychometric testing was performed before the start of ddC therapy and after 8 weeks.
  
  
  RESULTS
  During the 8 weeks of therapy with ddC alone, no neutropenia or anemia was observed; 6 of 9 patients had decreases in p24 antigen levels, and 8 of 15 had an increased CD4 cell count. At the 0.04 mg/kg level, a rash developed in three patients; mild mouth sores developed in 9 of 15 patients. On the alternating ddC/AZT schedule, no neuropathy was observed.
  
  
  CONCLUSIONS
  2',3'-Dideoxycytidine has antiretroviral activity in some children and appears to be safe for short intervals. Longer courses of ddC at lower dosage levels, and schedules integrating ddC into combination regimens, deserve to be explored.
authors.affiliation: Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: P A
authors.initials: PA
authors.lastname: Pizzo
authors.forename: K
authors.initials: K
authors.lastname: Butler
authors.forename: F
authors.initials: F
authors.lastname: Balis
authors.forename: E
authors.initials: E
authors.lastname: Brouwers
authors.forename: M
authors.initials: M
authors.lastname: Hawkins
authors.forename: J
authors.initials: J
authors.lastname: Eddy
authors.forename: M
authors.initials: M
authors.lastname: Einloth
authors.forename: J
authors.initials: J
authors.lastname: Falloon
authors.forename: R
authors.initials: R
authors.lastname: Husson
authors.forename: P
authors.initials: P
authors.lastname: Jarosinski
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000175:diagnosis / Q000188:drug therapy*; D000284:Administration, Oral; D000293:Adolescent; D000367:Age Factors; D015703:Antigens, CD / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009483:Neuropsychological Tests; D013997:Time Factors; D016047:Zalcitabine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D015215:Zidovudine / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D015215:Zidovudine; D016047:Zalcitabine