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 50 copies/ml were enrolled. In both stages, etravirine (4 mg/kg twice daily in stage I, 5.2 mg/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 (200 mg 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 757 ng/ml (680), respectively; area under the plasma concentration–time curve over 12 h was 4050 (3602) and 6141 ng h/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 5.2 mg/kg was well tolerated in this study and this dose was selected for further investigation in clinical trials.
aDepartment of Pediatrics and Adolescent Medicine, Johann Wolfgang Goethe-University, Frankfurt am Main
bDepartment of Pediatric Pneumology and Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany
cDepartment of Maternal and Pediatric Sciences, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan
dSan Martino Hospital, University of Genoa, Genoa, Italy
eTibotec Inc., Titusville, New Jersey, USA
fJohnson & Johnson Pharmaceutical Research and Development
gTibotec BVBA, Beerse, Belgium
hDepartment of Pediatrics, University of Padua, Padua, Italy.
*Raffaella Rosso deceased.
Correspondence to Christoph Königs, MD, Department of Pediatrics and Adolescent Medicine, Johann Wolfgang Goethe-University Hospital, Hs 32, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany. Tel: +49 69 6301 83030; fax: +49 69 6301 83991; e-mail: firstname.lastname@example.org
Received 14 July, 2011
Revised 11 November, 2011
Accepted 14 November, 2011
Data previously presented at the 15th Conference on Retroviruses and Opportunistic Infections (CROI): 3–6 February 2008, Boston, Massachusetts, USA (abstract 578) and the 16th CROI: 8–11 February 2009, Montreal, Canada (abstract 879).