title: Safety and efficacy of darunavir/ritonavir in treatment-experienced pediatric patients: week 48 results of the ARIEL trial.
abstract: BACKGROUND
  ARIEL (Darunavir in treatment-experienced pediatric population) was a phase II, open-label study assessing safety and antiviral activity of darunavir/ritonavir twice daily with an optimized background regimen (OBR) in treatment-experienced, HIV-1-infected pediatric patients (3 to <6 years, weighing 10 to <20 kg).
  
  
  METHODS
  The study consisted of an initial 4-week screening period, 48 weeks of treatment and a 4-week follow-up period. Patients initially received darunavir/ritonavir 20/3 mg/kg twice-daily for 2 weeks. Following review of pharmacokinetic, safety and antiviral data, the doses of darunavir/ritonavir were adjusted to 25/3 mg/kg twice-daily for patients <15 kg, and 375/50 mg twice-daily for patients 15 to <20 kg.
  
  
  RESULTS
  Of the 34 patients screened, 21 were treated (median treatment duration 48.6 weeks). Darunavir plus an OBR was well tolerated over 48 weeks, with no new safety concerns, and a comparable safety profile to that seen in older children and adults. All treatment-emergent lipid-related and glucose-related laboratory abnormalities were grade 1 or 2. At week 48, 17 of 21 patients (81.0%) had a confirmed virologic response (intent-to-treat, time-to-loss of virologic response). Improvements in height and weight were seen during the study.
  
  
  CONCLUSIONS
  No new safety concerns were observed over a 48 week period. These results led to lowering the age to 3 years at which darunavir/ritonavir is indicated for use in treatment-experienced pediatric patients. This study also established doses of darunavir to use in treatment-experienced, HIV-1-infected patients aged 3 to <6 years. A high virologic response was observed with this dose. No development of resistance was observed in patients who experienced virologic failure.
authors.affiliation: From the *Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; †Helios Salud, Buenos Aires, Argentina; ‡Gaitonade Center for AIDS Research and Education (YRG CARE), VHS, Chennai, India; §Department of Infectious Diseases, Hospital Geral De Nova Iguacu & Laboratório de AIDS e Imunologia Molecular, Fiocruz/IOC, Rio De Janeiro, Brazil; ¶Janssen Infectious Diseases BVBA, Beerse, Belgium; and ‖Janssen Research & Development LLC, Titusville, New Jersey.
authors.forename: Avy
authors.initials: A
authors.lastname: Violari
authors.forename: Rosa
authors.initials: R
authors.lastname: Bologna
authors.forename: Nagalingeswaran
authors.initials: N
authors.lastname: Kumarasamy
authors.forename: Jose Henrique
authors.initials: JH
authors.lastname: Pilotto
authors.forename: Annemie
authors.initials: A
authors.lastname: Hendrickx
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Kakuda
authors.forename: Erkki
authors.initials: E
authors.lastname: Lathouwers
authors.forename: Magda
authors.initials: M
authors.lastname: Opsomer
authors.forename: Tom
authors.initials: T
authors.lastname: Van de Casteele
authors.forename: Frank L
authors.initials: FL
authors.lastname: Tomaka
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D000069454:Darunavir / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D055118:Medication Adherence; D019438:Ritonavir / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D019438:Ritonavir; D000069454:Darunavir