Etravirine in treatment-experienced HIV-1-infected children 1 year to less than 6 years of age

Abstract

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: 2-12h 12h 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 AUC_12h12hr 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.