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

Publisher: Lippincott Williams & Wilkins Country of Publication: England NLM ID: 8710219 Publication Model: Print Cited Medium: Internet ISSN: 1473-5571 (Electronic) Linking ISSN: 02699370 NLM ISO Abbreviation: AIDS Subsets: MEDLINE

Publication: 1998- : London, England : Lippincott Williams & Wilkins
Original Publication: London : Gower Academic Journals, c1987-

Anti-HIV Agents*/adverse effects ; HIV Infections*/drug therapy ; HIV-1* ; Pyridazines*/therapeutic use; Adult ; Child ; Child, Preschool ; Humans ; Nitriles/therapeutic use ; Pyrimidines ; Ritonavir/therapeutic use ; Treatment Outcome

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 AUC12h 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 AUC12h 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 AUC12  h less than 2350 ng h/ml and underwent a dose increase. ETR AUC12  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.
(Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Comment in: AIDS. 2021 Jul 15;35(9):1497-1498. (PMID: 34185714)

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0 (Anti-HIV Agents)
0 (Nitriles)
0 (Pyridazines)
0 (Pyrimidines)
0C50HW4FO1 (etravirine)
O3J8G9O825 (Ritonavir)

Date Created: 20210408 Date Completed: 20210806 Latest Revision: 20230921

20240513

PMC8270511

10.1097/QAD.0000000000002902

33831904