title: Nevirapine concentrations in HIV-infected children treated with divided fixed-dose combination antiretroviral tablets in Malawi and Zambia.
abstract: OBJECTIVE
  To investigate nevirapine concentrations in African HIV-infected children receiving divided Triomune tablets (stavudine+lamivudine+nevirapine).
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  Steady-state plasma nevirapine concentrations were determined in Malawian and Zambian children aged 8 months to 18 years receiving Triomune in routine outpatient settings. Predictors from height-for-age, body mass index (BMI)-for-age, age, sex, post-dose sampling time and dose/m2/day were investigated using centre-stratified regression with backwards elimination (P<0.1).
  
  
  RESULTS
  Of the 71 Malawian and 56 Zambian children (median age 8.4 vs 8.5 years, height-for-age -3.15 vs -1.84, respectively), only 1 (3%) of those prescribed > or =300 mg/m2/day nevirapine had subtherapeutic concentrations (<3 mg/l) compared with 22 (23%) of those prescribed <300 mg/m2/day; most children with subtherapeutic nevirapine concentrations were taking half or quarter Triomune tablets. Lower nevirapine concentrations were independently associated with lower height-for-age (indicating stunting) (0.37 mg/l per unit higher [95% confidence interval (CI): -0.003, +0.74]; P=0.05), lower prescribed dose/m2 (+0.89 mg/l per 50 mg/m2 higher [95% CI: 0.32, 1.46]; P=0.002) and higher BMI-for-age (indicating lack of wasting) (-0.42 mg/l per unit higher [95% CI: -0.80, -0.04]; P=0.03).
  
  
  CONCLUSIONS
  Currently available adult fixed-dose combination tablets are not well suited to children, particularly at younger ages: Triomune 30 is preferable to Triomune 40 because of the higher dose of nevirapine relative to stavudine. Further research is required to confirm that concentrations are reduced in stunted children but increased in wasted children. Development of appropriate paediatric fixed-dose combination tablets is essential if antiretroviral therapy is to be made widely available to children in resource-limited settings.
authors.affiliation: Department of Paediatrics, College of Medicine, Blantyre, Malawi.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Ellis
authors.forename: Rafaella F A
authors.initials: RF
authors.lastname: L'homme
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Ewings
authors.forename: Veronica
authors.initials: V
authors.lastname: Mulenga
authors.forename: Frank
authors.initials: F
authors.lastname: Bell
authors.forename: Regina
authors.initials: R
authors.lastname: Chileshe
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Molyneux
authors.forename: Julia
authors.initials: J
authors.lastname: Abernethy
authors.forename: Joep J G
authors.initials: JJ
authors.lastname: van Oosterhout
authors.forename: Chifumbe
authors.initials: C
authors.lastname: Chintu
authors.forename: A Sarah
authors.initials: AS
authors.lastname: Walker
authors.forename: Diana M
authors.initials: DM
authors.lastname: Gibb
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004338:Drug Combinations; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007223:Infant; D019259:Lamivudine / Q000008:administration & dosage*; D008295:Malawi; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D018119:Stavudine / Q000008:administration & dosage*; D013607:Tablets; D016896:Treatment Outcome; D015024:Zambia
chemical_list: D019380:Anti-HIV Agents; D004338:Drug Combinations; D018894:Reverse Transcriptase Inhibitors; D013607:Tablets; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine