Etravirine in treatment-experienced HIV-1-infected children 1 year to less than 6 years of age.
AIDS
; 35(9): 1413-1421, 2021 07 15.
Article
em En
| MEDLINE
| ID: mdl-33831904
ABSTRACT
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 7-18âdays after starting ETR. Participants with ETR AUC12h less than 2350ângâh/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 3823ângâh/ml for cohort I and 3328ângâh/ml for cohort II. Seven children (33.3%) on the final dose, all taking ETR dispersed, had an AUC12â h less than 2350ângâh/ml and underwent a dose increase. ETR AUC12â 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 400âcopies/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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piridazinas
/
Infecções por HIV
/
HIV-1
/
Fármacos Anti-HIV
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article