Etravirine in treatment-experienced HIV-1-infected children 1 year to less than 6 years of age
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc..
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.
| Errataetall: |
CommentIn: AIDS. 2021 Jul 15;35(9):1497-1498. - PMID 34185714 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:35 |
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| Enthalten in: |
AIDS (London, England) - 35(2021), 9 vom: 15. Juli, Seite 1413-1421 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
MacBrayne, Christine E [VerfasserIn] |
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| Links: |
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| Themen: |
0C50HW4FO1 |
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| Anmerkungen: |
Date Completed 06.08.2021 Date Revised 21.09.2023 published: Print CommentIn: AIDS. 2021 Jul 15;35(9):1497-1498. - PMID 34185714 Citation Status MEDLINE |
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| doi: |
10.1097/QAD.0000000000002902 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM323870708 |
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| 041 | |a eng | ||
| 100 | 1 | |a MacBrayne, Christine E |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Etravirine in treatment-experienced HIV-1-infected children 1 year to less than 6 years of age |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 06.08.2021 | ||
| 500 | |a Date Revised 21.09.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a CommentIn: AIDS. 2021 Jul 15;35(9):1497-1498. - PMID 34185714 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. | ||
| 520 | |a OBJECTIVE: To describe the pharmacokinetics, safety, and efficacy of etravirine (ETR) in HIV-infected children 1 to less than 6 years of age | ||
| 520 | |a DESIGN: Phase I/II, open-label, multicenter, dose-finding study | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
| 650 | 7 | |a Nitriles |2 NLM | |
| 650 | 7 | |a Pyridazines |2 NLM | |
| 650 | 7 | |a Pyrimidines |2 NLM | |
| 650 | 7 | |a etravirine |2 NLM | |
| 650 | 7 | |a 0C50HW4FO1 |2 NLM | |
| 650 | 7 | |a Ritonavir |2 NLM | |
| 650 | 7 | |a O3J8G9O825 |2 NLM | |
| 700 | 1 | |a Rutstein, Richard M |e verfasserin |4 aut | |
| 700 | 1 | |a Wiznia, Andrew A |e verfasserin |4 aut | |
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| 700 | 1 | |a Moye, Jack |c Jr |e verfasserin |4 aut | |
| 700 | 1 | |a Costello, Diane G |e verfasserin |4 aut | |
| 700 | 1 | |a Reding, Christina A |e verfasserin |4 aut | |
| 700 | 1 | |a Barroso Hofer, Cristina |e verfasserin |4 aut | |
| 700 | 1 | |a Crauwels, Herta M |e verfasserin |4 aut | |
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| 700 | 1 | |a Tambuyzer, Lotke |e verfasserin |4 aut | |
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| 700 | 1 | |a Opsomer, Magda |e verfasserin |4 aut | |
| 700 | 1 | |a Kiser, Jennifer J |e verfasserin |4 aut | |
| 700 | 0 | |a and the IMPAACT P1090 Protocol Team |e verfasserin |4 aut | |
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