title: Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents.
abstract: OBJECTIVE
  To assess pharmacokinetics, safety and efficacy of darunavir/ritonavir (DRV/r) and optimized background regimen in treatment-experienced patients (6-17 years).
  
  
  METHODS
  Forty-eight-week, open-label, two-part, phase II study.
  
  
  METHODS
  In part I, 44 patients were randomized (1: 1 ratio) to receive a body weight-adjusted, adult-equivalent dose (group A) or a 20-33% higher DRV/r twice daily (b.i.d.) dose (group B). Pharmacokinetics, safety and efficacy were assessed following 2-week dosing (part I), which determined dosing for part II (evaluated 48-week safety and efficacy).
  
  
  RESULTS
  In part I, both groups met the protocol-specified criteria for pharmacokinetics and showed favorable tolerability and efficacy. The following body-weight doses were selected: DRV/r 375/50 mg b.i.d. (20-<30 kg), 450/60 mg b.i.d. (30-<40 kg) and 600/100 mg b.i.d. (> or =40 kg); these gave an AUC24h, C0h and Cmax of 102, 114 and 112%, respectively, versus the corresponding mean adult pharmacokinetic parameter. In part II, 80 patients received DRV/r (median age: 14 years, mean baseline HIV-1 RNA: 4.64 log(10)copies/ml). One patient (1%) discontinued (treatment-unrelated grade 3 anxiety). An abnormal mean baseline triglyceride level was normalized at 48 weeks (P < 0.01). At week 48, 65% had at least 1.0 log(10)HIV-1 RNA reduction; 59 and 48% achieved HIV-1 RNA less than 400 and less than 50 copies/ml, respectively (time-to-loss-of-virologic response). Mean age-adjusted weight z-score increased by 0.2 (P = 0.003).
  
  
  CONCLUSIONS
  In treatment-experienced children and adolescents, DRV/r showed comparable exposure to adults with appropriate dose selection, favorable safety and tolerability, improved body weight and significant virologic response. DRV/r is a valuable therapeutic option for this population.
authors.affiliation: Unité d'Immunologie Hématologie Pédiatrique, Hôpital Necker Enfants Malades, Assistance Publique-Hopitaux de Paris,149 Rue de Sèvres, Paris Cedex 15, France. blanche@necker.fr
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Rosa
authors.initials: R
authors.lastname: Bologna
authors.forename: Pedro
authors.initials: P
authors.lastname: Cahn
authors.forename: Sorin
authors.initials: S
authors.lastname: Rugina
authors.forename: Patricia
authors.initials: P
authors.lastname: Flynn
authors.forename: Claudia
authors.initials: C
authors.lastname: Fortuny
authors.forename: Peter
authors.initials: P
authors.lastname: Vis
authors.forename: Vanitha
authors.initials: V
authors.lastname: Sekar
authors.forename: Ben
authors.initials: B
authors.lastname: van Baelen
authors.forename: Inge
authors.initials: I
authors.lastname: Dierynck
authors.forename: Sabrina
authors.initials: S
authors.lastname: Spinosa-Guzman
mesh_terms: D000293:Adolescent; D002648:Child; D000069454:Darunavir; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D010349:Patient Compliance; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D013449:Sulfonamides; D019438:Ritonavir; D000069454:Darunavir