title: Efficacy and safety of darunavir/ritonavir at 48 weeks in treatment-naïve, HIV-1-infected adolescents: results from a phase 2 open-label trial (DIONE).
abstract: BACKGROUND
  Twice-daily darunavir/ritonavir is indicated in treatment-experienced children (≥3 years). This study assessed once-daily administration in treatment-naïve adolescents.
  
  
  METHODS
  Phase 2, 48-week, open-label, single-arm study evaluating pharmacokinetics, safety and efficacy of once-daily darunavir/ritonavir 800/100 mg in treatment-naïve, HIV-1-infected adolescents (≥12 to <18 years, ≥40 kg) with zidovudine/lamivudine or abacavir/lamivudine.
  
  
  RESULTS
  Twelve patients (67% female; median 14.4 years) were enrolled. After 24 and 48 weeks, respectively, 11 of 12 (92%) and 10 of 12 (83%) patients achieved viral load <50 copies/mL (intent-to-treat time-to-loss of virologic response); all had ≥1 log10 drop in viral load versus baseline. Median CD4 cell count increased by 175 and 221 cells/mm (intent-to-treat-noncompleter = failure) after 24 and 48 weeks, respectively. Eighty-three percent of patients were adherent to darunavir/ritonavir. One patient was never suppressed and 1 patient rebounded. No patients developed darunavir resistance-associated mutations or lost phenotypic susceptibility to any commercially available protease inhibitor or any background nucleoside reverse transcriptase inhibitor. Eleven patients (92%) reported ≥1 adverse event (AE), considered in 2 patients to be at least possibly related to darunavir (gastrointestinal-related events and dizziness). Four patients had ≥1 serious AE. Three patients reported ≥1 grade 3/4 AE; no serious or grade 3/4 AEs were considered darunavir related. No patients discontinued because of AEs.
  
  
  CONCLUSIONS
  Over 48 weeks, once-daily darunavir/ritonavir 800/100 mg plus NRTIs was effective and well-tolerated for treatment of HIV-1-infected, antiretroviral-naïve adolescents (≥12 to <18 years). These findings support use of once-daily darunavir/ritonavir 800/100 mg in this population.
authors.affiliation: From the *Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN; †Clinic for Treatment of HIV-infected Children, Kiev Children's Hospital, Kiev, Ukraine; ‡Department of Pediatric Immuno-Hematology, Hôpital Necker-Enfants Malades, Paris, France; §Department of Paediatrics, University of Padova, Padova, Italy; ¶Department of Pediatrics, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain; ‖Department of Pediatrics, Birmingham Heartlands Hospital, Birmingham, United Kingdom; **Janssen Research & Development LLC, Titusville, NJ; and ††Janssen Research & Development, Beerse, Belgium.
authors.forename: Patricia
authors.initials: P
authors.lastname: Flynn
authors.forename: Svitlana
authors.initials: S
authors.lastname: Komar
authors.forename: Stephane
authors.initials: S
authors.lastname: Blanche
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
authors.forename: Antoni
authors.initials: A
authors.lastname: Noguera-Julian
authors.forename: Steven
authors.initials: S
authors.lastname: Welch
authors.forename: Erkki
authors.initials: E
authors.lastname: Lathouwers
authors.forename: Tom
authors.initials: T
authors.lastname: Van de Casteele
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Kakuda
authors.forename: Magda
authors.initials: M
authors.lastname: Opsomer
mesh_terms: D000293:Adolescent; D000740:Anemia / Q000139:chemically induced; D018791:CD4 Lymphocyte Count; D000069454:Darunavir; D015224:Dideoxynucleosides / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D055118:Medication Adherence; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019438:Ritonavir / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors; D019562:Viral Load / Q000187:drug effects; D014839:Vomiting / Q000139:chemically induced; D015215:Zidovudine / Q000627:therapeutic use; D000099227:Abacavir
chemical_list: D000069454:Darunavir; D015224:Dideoxynucleosides; D017320:HIV Protease Inhibitors; D019259:Lamivudine; D018894:Reverse Transcriptase Inhibitors; D019438:Ritonavir; D013449:Sulfonamides; D015215:Zidovudine; D000099227:Abacavir