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

• Published in: AIDS (London) Vol. 35; no. 9; pp. 1413 - 1421
• Main Authors: MacBrayne, Christine E., Rutstein, Richard M., Wiznia, Andrew A., Graham, Bobbie, Alvero, Carmelita G., Fairlie, Lee, Lypen, Kathryn, George, Kathleen H., Townley, Ellen, Moye, Jack, Costello, Diane G., Reding, Christina A., Barroso Hofer, Cristina, Crauwels, Herta M., Woot de Trixhe, Xavier, Tambuyzer, Lotke, Vanveggel, Simon, Opsomer, Magda, Kiser, Jennifer J.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 15.07.2021
• Subjects: Clinical Science
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0000000000002902

Objective: To describe the pharmacokinetics, safety, and efficacy of etravirine (ETR) in HIV-infected children 1 to less than 6 years of age. Design: Phase I/II, open-label, multicenter, dose-finding study. Methods: Antiretroviral therapy (ART)-experienced children in two age cohorts (I: 2 to <6 years; II: 1 to less than 2 years) received weight-based ETR, swallowed whole or dispersed in liquid, with optimized ART including a ritonavir-boosted protease inhibitor. Intensive pharmacokinetics occurred 7–18 days after starting ETR. Participants with ETR AUC 12h less than 2350 ng h/ml had a dose increase and repeat pharmacokinetics. Results: Twenty-six children enrolled and 21 (15 in cohort I and 6 in cohort II) had evaluable intensive pharmacokinetics sampling at the final weight-based dose. On the final dose, the geometric mean ETR AUC 12h was 3823 ng h/ml for cohort I and 3328 ng h/ml for cohort II. Seven children (33.3%) on the final dose, all taking ETR dispersed, had an AUC 12 h less than 2350 ng h/ml and underwent a dose increase. ETR AUC 12 h was 3.8-fold higher when ETR was swallowed whole vs. dispersed, P less than 0.0001. On the final dose, 75 and 33.3% in cohorts I and II, respectively, had HIV-1 RNA 400 copies/ml or less or at least 2 log reductions from baseline at week 48. Three children (11.5%) experienced a grade at least 3 adverse event related to ETR but only 1 discontinued. Conclusion: ETR was well tolerated. Predefined pharmacokinetics 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 to more than 6 years but not in those less than 2 years.