Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents

AIDS. 2009 Sep 24;23(15):2005-13. doi: 10.1097/QAD.0b013e328330abaa.

Abstract

Objective: To assess pharmacokinetics, safety and efficacy of darunavir/ritonavir (DRV/r) and optimized background regimen in treatment-experienced patients (6-17 years).

Design: 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).

Conclusion: 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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Darunavir
  • Drug Administration Schedule
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / adverse effects
  • HIV Protease Inhibitors / blood*
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • HIV-1 / isolation & purification*
  • Humans
  • Patient Compliance
  • RNA, Viral / blood
  • Ritonavir / administration & dosage
  • Ritonavir / adverse effects
  • Ritonavir / blood*
  • Ritonavir / therapeutic use
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects
  • Sulfonamides / blood*
  • Sulfonamides / therapeutic use
  • Treatment Outcome
  • Viral Load

Substances

  • HIV Protease Inhibitors
  • RNA, Viral
  • Sulfonamides
  • Ritonavir
  • Darunavir