title: Antiviral efficacy, tolerability and pharmacokinetics of efavirenz in an unselected cohort of HIV-infected children.
abstract: OBJECTIVE
  To obtain data on the pharmacokinetics of efavirenz in children in clinical practice.
  
  
  METHODS
  HIV-1-infected children received efavirenz capsules or tablets in accordance with manufacturer's dosing recommendations. Plasma was collected at regular visits and analysed by HPLC. The therapeutic range of efavirenz was defined as 1.0-4.0 mg/L.
  
  
  RESULTS
  Thirty-three children were included. Median (range) age, body weight, dose and dose/kg were 8.2 (2.1-16.7) years, 24 (12-62) kg, 300 (200-800) mg and 13.3 (9.7-22.5) mg/kg, respectively. Median (range) efavirenz plasma concentration at first sampling was 2.8 (0.13-11.6) mg/L. Plasma concentrations were not dependent on age (P = 0.97) or dose/kg (P = 0.87). A total of 307 efavirenz plasma concentrations were determined. Forty-five samples (14.7%) contained >4.0 mg/L, and 27 samples (8.8%) contained <1.0 mg/L. Eight children (24%) reported persistent adverse events probably caused by efavirenz [concentration problems (5), sleep disorder (1), psychotic reaction (1) and seizure (1)]; six discontinued efavirenz for this reason. A non-significant trend existed towards a higher proportion of toxic efavirenz plasma concentrations (>4.0 mg/L) in subjects who reported efavirenz adverse events: 25.9% versus 12.8% (P = 0.23; t-test). Viral load was <50 copies/mL in all 27 subjects who continued efavirenz, despite occasional subtherapeutic efavirenz plasma concentrations in 12 children. The occasional subtherapeutic levels suggest that temporal non-adherence was present.
  
  
  CONCLUSIONS
  Efavirenz as part of highly active antiretroviral therapy was highly effective in children able to tolerate the drug. Therapeutic drug monitoring (TDM) as part of toxicity management may prevent discontinuation in a subset of patients. Temporal non-adherence occurs frequently. TDM may allow initiation of adherence interventions before viral load becomes detectable.
authors.affiliation: Department of Immunodeficiency Diseases, Childrens Hospital of the Ludwig Maximilians University, Munich, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Wintergerst
authors.forename: F
authors.initials: F
authors.lastname: Hoffmann
authors.forename: A
authors.initials: A
authors.lastname: Jansson
authors.forename: G
authors.initials: G
authors.lastname: Notheis
authors.forename: K
authors.initials: K
authors.lastname: Huss
authors.forename: M
authors.initials: M
authors.lastname: Kurowski
authors.forename: D
authors.initials: D
authors.lastname: Burger
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001288:Attention / Q000187:drug effects; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003521:Cyclopropanes; D020920:Dyssomnias / Q000139:chemically induced; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008657:Metabolic Clearance Rate; D010949:Plasma / Q000737:chemistry; D011618:Psychotic Disorders; D012640:Seizures / Q000139:chemically induced; D016896:Treatment Outcome; D016312:Treatment Refusal; D019562:Viral Load
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; C098320:efavirenz