title: Etravirine in treatment-experienced, HIV-1-infected children and adolescents: 48-week safety, efficacy and resistance analysis of the phase II PIANO study.
abstract: OBJECTIVE
  PIANO (Paediatric study of Intelence As an NNRTI Option; TMC125-C213; NCT00665847) assessed the safety/tolerability, antiviral activity and pharmacokinetics of etravirine plus an optimized background regimen (OBR) in treatment-experienced, HIV-1-infected children (≥ 6 to < 12 years) and adolescents (≥ 12 to < 18 years) over 48 weeks.
  
  
  METHODS
  In a phase II, open-label, single-arm study, 101 treatment-experienced patients (41 children; 60 adolescents) with screening viral load (VL) ≥ 500 HIV-1 RNA copies/mL received etravirine 5.2 mg/kg (maximum dose 200 mg) twice a day (bid) plus OBR.
  
  
  RESULTS
  Sixty-seven per cent of patients had previously used efavirenz or nevirapine. At week 48, the most common treatment-related grade ≥ 2 adverse event (AE) was rash (13%); 12% experienced grade 3 AEs. Only two grade 4 AEs occurred (both thrombocytopaenia, not etravirine related). At week 48, 56% of patients (68% children; 48% adolescents) achieved a virological response (VL<50 copies/mL; intent-to-treat, noncompleter=failure). Factors predictive of response were adherence > 95%, male sex, low baseline etravirine weighted genotypic score and high etravirine trough concentration (C0h ). Seventy-six patients (75%) completed the trial; most discontinuations occurred because of protocol noncompliance or AEs (8% each). Sixty-five per cent of patients were > 95% adherent by questionnaire and 39% by pill count. Forty-one patients experienced virological failure (VF; time-to-loss-of-virological-response non-VF-censored algorithm) (29 nonresponders; 12 rebounders). Of 30 patients with VF with paired baseline/endpoint genotypes, 18 (60%) developed nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations, most commonly Y181C. Mean etravirine area under the plasma concentration-time curve over 12 h (AUC0-12h ; 5216 ng h/mL) and C0h (346 ng/mL) were comparable to adult target values.
  
  
  CONCLUSIONS
  Results with etravirine 5.2 mg/kg bid (with OBR) in this treatment-experienced paediatric population and etravirine 200 mg bid in treatment-experienced adults were comparable. Etravirine is an NNRTI option for treatment-experienced paediatric patients.
authors.affiliation: Imperial College, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Tudor-Williams
authors.forename: P
authors.initials: P
authors.lastname: Cahn
authors.forename: K
authors.initials: K
authors.lastname: Chokephaibulkit
authors.forename: J
authors.initials: J
authors.lastname: Fourie
authors.forename: C
authors.initials: C
authors.lastname: Karatzios
authors.forename: S
authors.initials: S
authors.lastname: Dincq
authors.forename: M
authors.initials: M
authors.lastname: Opsomer
authors.forename: T N
authors.initials: TN
authors.lastname: Kakuda
authors.forename: S
authors.initials: S
authors.lastname: Nijs
authors.forename: L
authors.initials: L
authors.lastname: Tambuyzer
authors.forename: F L
authors.initials: FL
authors.lastname: Tomaka
mesh_terms: D000293:Adolescent; D019540:Area Under Curve; D002648:Child; D003875:Drug Eruptions; D024882:Drug Resistance, Viral / Q000187:drug effects* / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008297:Male; D055118:Medication Adherence; D009154:Mutation; D019829:Nevirapine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009570:Nitriles; D011724:Pyridazines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine; D019829:Nevirapine
keywords: HIV; efficacy; etravirine; paediatrics; safety