879 
Pharmacokinetics and Dose Selection of Etravirine in HIV-infected Children between 6 and 17 Years, Inclusive
Christoph Königs*1, C Feiterna-Sperling2, S Esposito3, C Giaquinto4, T Kakuda5, R Sinha6, R MacK5, K Janssen6, and R Hoetelmans6
1J W Goethe Univ, Frankfurt, Germany; 2Klinikum Humboldt University, Berlin, Germany; 3Università di Milano, Milan, Italy; 4Università di Padova, Padova, Italy; 5Tibotec, Inc, Yardley, PA, US; and 6Tibotec BVBA, Mechelen, Belgium
Background: Etravirine (ETR) is a NNRTI approved in
combination with other ARV for the treatment of HIV-infected
treatment-experienced adults. Pediatric dosing of ETR has not been established.
The primary objective of this phase I open-label trial was to determine the
weight-based dose of ETR that will achieve exposures in treatment-experienced
children comparable to those in adults.
Methods: HIV-1-infected children between 6 and
≤17 years with at least 2 consecutive viral loads <50 copies/mL on a
stable lopinavir/ritonavir (LPV/r) -containing regimen were enrolled;
concomitant NNRTI use was excluded. The trial was conducted in two sequential stages.
In both stages, ETR was added for 7 days followed by a morning dose and 12-hour
pharmacokinetic assessment on day 8. ETR was administered following a meal and
dosed 4 mg/kg twice daily in stage I and 5.2 mg/kg twice daily in stage II; 25-
and 100-mg tablets were used. ETR pharmacokinetics were assessed using
non-compartmental analysis; pharmacokinetic parameters were compared to those
previously established in HIV-1-infected adults. Safety and tolerability were
assessed throughout the study up to 30 days post-dosing.
Results: We enrolled 21 children into each stage (7
children participated in both stages); pharmacokinetic were available in 19 and
20 in stages I and II, respectively. The mean (SD) Cmax in stage I
and II, respectively, was 495 (453) ng/mL and 757 (680) ng/mL; Cmin
was 184 (151) and 294 (278) ng/mL; and AUC12h was 4050 (3602) and
6141 (5586) ng•h/mL. Pharmacokinetic parameters in Stage II were more
comparable to adults participating in the phase III DUET-1 and -2 trials (mean
[SD] population derived Cmin was 393 [391] ng/mL and AUC12h
was 5506 [4710] ng•h/mL, n = 575). All children remained <50 copies/mL on day
8. No serious adverse events occurred during ETR treatment; 14 and 9 children
in stage I and II, respectively, reported at least 1 adverse event, mostly grade
1 or 2. Two children in stage I developed a mild (grade 1) or moderate (grade
2) rash; no rash was reported in stage II.
Conclusions: The proposed dose of ETR in children 6
to 17 years inclusive is 5.2 mg/kg twice daily. This dose provides comparable
exposure to the adult dose of ETR (200 mg twice daily) and was generally safe
and well tolerated. Further pharmacokinetic, safety, and tolerability of ETR in
this population will be investigated in the phase II trial PIANO (Pediatric
trial with Intelence as an Active NNRTI Option).
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