title: Pharmacokinetics, safety, and 48-week efficacy of oral raltegravir in HIV-1-infected children aged 2 through 18 years.
abstract: BACKGROUND
  IMPAACT P1066 is a phase I/II open-label multicenter trial to evaluate pharmacokinetics, safety, tolerability, and efficacy of multiple raltegravir formulations in human immunodeficiency virus (HIV)-infected youth.
  
  
  METHODS
  Dose selection for each cohort (I: 12 to <19 years; II: 6 to <12 years; and III: 2 to <6 years) was based on review of short-term safety (4 weeks) and intensive pharmacokinetic evaluation. Safety data through weeks 24 and 48, and grade ≥ 3 or serious adverse events (AEs) were assessed. The primary virologic endpoint was achieving HIV RNA <400 copies/mL or ≥ 1 log10 reduction between baseline and week 24.
  
  
  RESULTS
  The targeted pharmacokinetic parameters (AUC0-12h and C12h) were achieved for each cohort, allowing dose selection for 2 formulations. Of 96 final dose subjects, there were 15 subjects with grade 3 or higher clinical AEs (1 subject with drug-related [DR] psychomotor hyperactivity and insomnia); 16 subjects with grade 3 or higher laboratory AEs (1 with DR transaminase elevation); 14 subjects with serious clinical AEs (1 with DR rash); and 1 subjects with serious laboratory AEs (1 with DR transaminase increased). There were no discontinuations due to AEs and no DR deaths. Favorable virologic responses at week 48 were observed in 79.1% of patients, with a mean CD4 increase of 156 cells/µL (4.6%).
  
  
  CONCLUSIONS
  Raltegravir as a film-coated tablet 400 mg twice daily (6 to <19 years, and ≥ 25 kg) and chewable tablet 6 mg/kg (maximum dose 300 mg) twice daily (2 to <12 years) was well tolerated and showed favorable virologic and immunologic responses.
  
  
  BACKGROUND
  NCT00485264.
authors.affiliation: Department of Pediatrics, State University of New York at Stony Brook.
authors.forename: Sharon
authors.initials: S
authors.lastname: Nachman
authors.forename: Nan
authors.initials: N
authors.lastname: Zheng
authors.forename: Edward P
authors.initials: EP
authors.lastname: Acosta
authors.forename: Hedy
authors.initials: H
authors.lastname: Teppler
authors.forename: Brenda
authors.initials: B
authors.lastname: Homony
authors.forename: Bobbie
authors.initials: B
authors.lastname: Graham
authors.forename: Terence
authors.initials: T
authors.lastname: Fenton
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.forename: Larissa
authors.initials: L
authors.lastname: Wenning
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Spector
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Frenkel
authors.forename: Carmelita
authors.initials: C
authors.lastname: Alvero
authors.forename: Carol
authors.initials: C
authors.lastname: Worrell
authors.forename: Edward
authors.initials: E
authors.lastname: Handelsman
authors.forename: Andrew
authors.initials: A
authors.lastname: Wiznia
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D008297:Male; D011760:Pyrrolidinones / Q000008:administration & dosage* / Q000009:adverse effects*; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium
keywords: adverse event; pediatric HIV; pharmacokinetics; raltegravir