Pharmacokinetics and short-term safety and tolerability of etravirine in treatment-experienced HIV-1-infected children and adolescents

Christoph Königs, Cornelia Feiterna-Sperling, Susanna Esposito, Claudio Viscoli, Raffaella Rosso, Thomas N. Kakuda, Ruud Leemans, Monika Peeters, Rebecca MacK, Ingeborg Peeters, Rekha Sinha, Katia Boven, Carlo Giaquinto

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: To evaluate the pharmacokinetics, weight-based dose selection and short-term safety and tolerability of etravirine in HIV-1-infected children and adolescents. Design: Phase I, nonrandomized, open-label study in two stages. Methods: Children and adolescents aged at least 6 years to 17 years or less on a stable lopinavir/ritonavir-based antiretroviral regimen with HIV-1 RNA plasma viral load less than 50copies/ml were enrolled. In both stages, etravirine (4mg/kg twice daily in stage I, 5.2mg/kg twice daily in stage II), added to the existing antiretroviral regimen, was administered for 7 days followed by a morning dose and 12-h pharmacokinetic assessment on day 8. Pharmacokinetic parameters were determined using noncompartmental analysis. Data were compared with those previously established in HIV-1-infected adults on a similar etravirine (200mg twice daily) combination antiretroviral regimen. Results: Twenty-one patients were recruited to each stage; 19 and 20 had evaluable pharmacokinetics in stages I and II, respectively. Mean (SD) maximum plasma concentrations in stages I and II were 495 (453) and 757ng/ml (680), respectively; area under the plasma concentration-time curve over 12h was 4050 (3602) and 6141ngh/ml (5586), respectively. Statistical/qualitative comparisons showed comparable exposures with adults in stage II; however, the upper 90% confidence interval fell outside the predefined range. Plasma viral load remained undetectable on day 8 in all patients, and etravirine was well tolerated at both doses. CONCLUSION:: Etravirine 5.2mg/kg was well tolerated in this study and this dose was selected for further investigation in clinical trials.

Original languageEnglish
Pages (from-to)447-455
Number of pages9
JournalAIDS (London, England)
Volume26
Issue number4
DOIs
Publication statusPublished - Feb 20 2012

Keywords

  • children
  • etravirine
  • HIV-1
  • pediatric
  • pharmacokinetics
  • phase I

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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