title: Toxicity and efficacy of daily vs. weekly dapsone for prevention of Pneumocystis carinii pneumonia in children infected with human immunodeficiency virus. ACTG 179 Study Team. AIDS Clinical Trials Group.
abstract: BACKGROUND
  Dapsone is an alternative drug for Pneumocystis carinii pneumonia (PCP) prophylaxis in individuals intolerant to trimethoprim-sulfamethoxazole (T/S). There are, however, few data on the pharmacokinetics, toxicity or efficacy of dapsone in children. Design. Randomized, multicenter trial comparing daily (1 or 2 mg/kg) with weekly (4 mg/kg) dapsone regimens in 94 HIV-infected children intolerant to T/S.
  
  
  METHODS
  Hematologic and hepatic toxicity was monitored, as well as the occurrence of skin rash, PCP or death.
  
  
  RESULTS
  Initial pharmacokinetic data indicated that adequate serum dapsone concentrations were not achieved with the daily 1-mg/kg regimen; the daily dose was then increased to 2 mg/kg. Both short and long term hematologic toxicities were marginally greater in children receiving the daily 2 mg/kg compared with the weekly regimen. Allergic skin rashes were similar in children receiving the daily and weekly regimens (17% in both) and were not associated with prior history of rash with T/S. PCP occurred most frequently with the daily 1-mg/kg regimen (22.0 cases/100 patient years), least frequently with the daily 2-mg/kg regimen (0 case/100 patient years) and at intermediate frequency with the weekly regimen (9.5 cases/100 patient years). More deaths were observed in patients receiving the daily than the weekly regimen (8 vs. 2, respectively), although the deaths were not directly attributable to dapsone treatment.
  
  
  CONCLUSIONS
  Although a weekly dapsone regimen of 4 mg/kg produced less hematologic toxicity than a daily regimen of 2 mg/kg, this advantage was offset by a trend toward higher breakthrough rates of PCP.
authors.affiliation: Children's Hospital, Division of Infectious Diseases, Boston, MA 02115, USA. mcintosh@a1.tch.harvard.edu
authors.forename: K
authors.initials: K
authors.lastname: McIntosh
authors.forename: E
authors.initials: E
authors.lastname: Cooper
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: M
authors.initials: M
authors.lastname: Mirochnick
authors.forename: J
authors.initials: J
authors.lastname: Lindsey
authors.forename: D
authors.initials: D
authors.lastname: Jacobus
authors.forename: L
authors.initials: L
authors.lastname: Mofenson
authors.forename: R
authors.initials: R
authors.lastname: Yogev
authors.forename: S A
authors.initials: SA
authors.lastname: Spector
authors.forename: J L
authors.initials: JL
authors.lastname: Sullivan
authors.forename: H
authors.initials: H
authors.lastname: Sacks
authors.forename: A
authors.initials: A
authors.lastname: Kovacs
authors.forename: S
authors.initials: S
authors.lastname: Nachman
authors.forename: J
authors.initials: J
authors.lastname: Sleasman
authors.forename: V
authors.initials: V
authors.lastname: Bonagura
authors.forename: J
authors.initials: J
authors.lastname: McNamara
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control*; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003622:Dapsone / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D006801:Humans; D007223:Infant; D011020:Pneumonia, Pneumocystis / Q000517:prevention & control*; D012044:Regression Analysis
chemical_list: D000890:Anti-Infective Agents; D003622:Dapsone