Etravirine in treatment-experienced HIV-1 infected children 1-<6 years of age.

OBJECTIVE To describe the pharmacokinetics (PK), safety, and efficacy of etravirine (ETR) in HIV-infected children 1 to < 6 yrs. DESIGN Phase I/II, open label, multicenter, dose-finding study. METHODS Antiretroviral (ARV)-experienced children in two age cohorts (I: 2-<6 yr; II: 1-<2 yr) received weight-based ETR, swallowed whole or dispersed in liquid, with optimized ARV therapy including a ritonavir-boosted protease inhibitor. Intensive PK occurred 7-18 days after starting ETR. Participants with ETR AUC12h <2,350 ng*hr/mL had a dose increase and repeat PK. RESULTS Twenty-six children enrolled and 21 (15 in Cohort I and 6 in Cohort II) had evaluable intensive PK sampling at the final weight-based dose. On the final dose, the geometric mean ETR AUC12h was 3,823 ng*hr/mL for Cohort I and 3,328 ng*hr/mL for Cohort II. Seven children (33.3%) on the final dose, all taking ETR dispersed, had an AUC12h<2,350 ng*hr/mL and underwent a dose increase. ETR AUC12hr was 3.8-fold higher when ETR was swallowed whole vs. dispersed, p<0.0001. On the final dose, 75.0% and 33.3% in cohorts I and II, respectively had HIV-1 RNA ≤400 copies/mL or ≥2 log reductions from baseline at Week 48. Three children (11.5%) experienced a Grade ≥3 adverse event related to ETR, but only 1 discontinued. CONCLUSIONS ETR was safe and well-tolerated. Predefined PK targets were met, but overall exposures were low vs. historical data in adults, particularly in young children taking dispersed tablets. A high rate of viral efficacy was observed among those aged 2-<6 yr, but not in those <2 yrs.