title: Efficacy, safety and pharmacokinetics of tenofovir disoproxil fumarate in virologic-suppressed HIV-infected children using weight-band dosing.
abstract: BACKGROUND
  Tenofovir disoproxil fumarate (TDF) is approved for children but concerns remain about long-term renal and bone toxicity. We evaluated the efficacy, safety and pharmacokinetics of TDF in treatment-experienced children during 96 weeks.
  
  
  METHODS
  This was a prospective, open-label study in HIV-infected children 3-18 years of age (≥15 kg), with viral suppression on their first-line regimen without tenofovir. Children were given TDF/lamivudine/efavirenz once daily at entry; TDF was prescribed according to weight bands. Age-, gender- and CD4-matched controls receiving TDF-sparing regimens were concomitantly enrolled. Tenofovir pharmacokinetic assessment was performed at week 4. CD4 counts, HIV-1 RNA viral load and safety assessments were determined at baseline, 24, 48 and 96 weeks.
  
  
  RESULTS
  Eighty children were enrolled (40 per group); 35 (44%) were male. Median age was 12.2 (range 3.1-17.7) years. The median administered dose was 214 mg/m. Tenofovir geometric mean AUC0-24 hours, Cmax and C24 hours were 2.66 [90% confidence interval (CI) 2.49-2.84] μg hours/mL, 0.26 (0.24-0.29) μg/mL and 0.057 (0.052-0.062) μg/mL, respectively. Estimated glomerular filtration rate did not significantly change overtime. The fractional excretion of calcium slightly increased but fractional excretion of phosphate was unchanged among children in TDF group. The bone mineral density Z score decreased in the first 24 weeks of TDF treatment and was stable afterward. The TDF group had lower cholesterol levels (P = 0.001). Thirty-nine of 40 children remained virologically suppressed. No serious adverse event related to tenofovir.
  
  
  CONCLUSIONS
  TDF substitution in children and adolescents who were otherwise stable while receiving a first-line nonnucleoside reverse transcriptase inhibitor-based regimen achieved adequate exposure without clinically significant renal or bone adverse events over 96 weeks. While reassuring, these preliminary safety findings may not exclude delayed effects on renal function and bone density.
authors.affiliation: From the *Research Institute for Health Sciences and † Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; ‡Harvard School of Public Health, Boston, Massachusetts; §Institut de Recherche pour le Développement, Marseille, France; ¶Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; and ‖Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Linda
authors.initials: L
authors.lastname: Aurpibul
authors.forename: Tim R
authors.initials: TR
authors.lastname: Cressey
authors.forename: Sirintip
authors.initials: S
authors.lastname: Sricharoenchai
authors.forename: Orasri
authors.initials: O
authors.lastname: Wittawatmongkol
authors.forename: Virat
authors.initials: V
authors.lastname: Sirisanthana
authors.forename: Wanatpreeya
authors.initials: W
authors.lastname: Phongsamart
authors.forename: Tavitiya
authors.initials: T
authors.lastname: Sudjaritruk
authors.forename: Kulkanya
authors.initials: K
authors.lastname: Chokephaibulkit
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000293:Adolescent; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects; D015519:Bone Density; D018791:CD4 Lymphocyte Count; D002118:Calcium / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003521:Cyclopropanes; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D000068698:Tenofovir; D016896:Treatment Outcome; D016482:Urinalysis; D019562:Viral Load
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D063065:Organophosphonates; D012367:RNA, Viral; D019259:Lamivudine; D000068698:Tenofovir; D000225:Adenine; C098320:efavirenz; D002118:Calcium