Rifabutin pharmacokinetics and safety among TB/HIV-coinfected children receiving lopinavir/ritonavir-containing second-line ART
© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy..
BACKGROUND: Treatment options are limited for TB/HIV-coinfected children who require PI-based ART. Rifabutin is the preferred rifamycin for adults on PIs, but the one study evaluating rifabutin with PIs among children was stopped early due to severe neutropenia.
METHODS: We evaluated rifabutin safety and plasma pharmacokinetics among coinfected children 3-15 years of age receiving rifabutin 2.5 mg/kg daily with standard doses of lopinavir/ritonavir. The AUC0-24 at 2, 4 and 8 weeks after rifabutin initiation was described using intensive sampling and non-compartmental analysis. Clinical and laboratory toxicities were intensively monitored at 12 visits throughout the study.
RESULTS: Among 15 children with median (IQR) age 13.1 (10.9-14.0) years and weight 25.5 (22.3-30.5) kg, the median (IQR) rifabutin AUC0-24 was 5.21 (4.38-6.60) μg·h/mL. Four participants had AUC0-24 below 3.8 μg·h/mL (a target for the population average exposure) at week 2 and all had AUC0-24 higher than 3.8 μg·h/mL at the 4 and 8 week visits. Of 506 laboratory evaluations during rifabutin, grade 3 and grade 4 abnormalities occurred in 16 (3%) and 2 (0.4%) instances, respectively, involving 9 (60%) children. Specifically, grade 3 (n = 4) and grade 4 (n = 1) neutropenia resolved without treatment interruption or clinical sequelae in all patients. One child died at week 4 of HIV-related complications.
CONCLUSIONS: In children, rifabutin 2.5 mg/kg daily achieved AUC0-24 comparable to adults and favourable HIV and TB treatment outcomes were observed. Severe neutropenia was relatively uncommon and improved with ongoing rifabutin therapy. These data support the use of rifabutin for TB/HIV-coinfected children who require lopinavir/ritonavir.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:76 |
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| Enthalten in: |
The Journal of antimicrobial chemotherapy - 76(2021), 3 vom: 11. Feb., Seite 710-717 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rawizza, Holly E [VerfasserIn] |
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| Links: |
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| Themen: |
1W306TDA6S |
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| Anmerkungen: |
Date Completed 05.07.2021 Date Revised 06.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/jac/dkaa512 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM318604213 |
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| 100 | 1 | |a Rawizza, Holly E |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Rifabutin pharmacokinetics and safety among TB/HIV-coinfected children receiving lopinavir/ritonavir-containing second-line ART |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 05.07.2021 | ||
| 500 | |a Date Revised 06.03.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. | ||
| 520 | |a BACKGROUND: Treatment options are limited for TB/HIV-coinfected children who require PI-based ART. Rifabutin is the preferred rifamycin for adults on PIs, but the one study evaluating rifabutin with PIs among children was stopped early due to severe neutropenia | ||
| 520 | |a METHODS: We evaluated rifabutin safety and plasma pharmacokinetics among coinfected children 3-15 years of age receiving rifabutin 2.5 mg/kg daily with standard doses of lopinavir/ritonavir. The AUC0-24 at 2, 4 and 8 weeks after rifabutin initiation was described using intensive sampling and non-compartmental analysis. Clinical and laboratory toxicities were intensively monitored at 12 visits throughout the study | ||
| 520 | |a RESULTS: Among 15 children with median (IQR) age 13.1 (10.9-14.0) years and weight 25.5 (22.3-30.5) kg, the median (IQR) rifabutin AUC0-24 was 5.21 (4.38-6.60) μg·h/mL. Four participants had AUC0-24 below 3.8 μg·h/mL (a target for the population average exposure) at week 2 and all had AUC0-24 higher than 3.8 μg·h/mL at the 4 and 8 week visits. Of 506 laboratory evaluations during rifabutin, grade 3 and grade 4 abnormalities occurred in 16 (3%) and 2 (0.4%) instances, respectively, involving 9 (60%) children. Specifically, grade 3 (n = 4) and grade 4 (n = 1) neutropenia resolved without treatment interruption or clinical sequelae in all patients. One child died at week 4 of HIV-related complications | ||
| 520 | |a CONCLUSIONS: In children, rifabutin 2.5 mg/kg daily achieved AUC0-24 comparable to adults and favourable HIV and TB treatment outcomes were observed. Severe neutropenia was relatively uncommon and improved with ongoing rifabutin therapy. These data support the use of rifabutin for TB/HIV-coinfected children who require lopinavir/ritonavir | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
| 650 | 7 | |a Rifabutin |2 NLM | |
| 650 | 7 | |a 1W306TDA6S |2 NLM | |
| 650 | 7 | |a Lopinavir |2 NLM | |
| 650 | 7 | |a 2494G1JF75 |2 NLM | |
| 650 | 7 | |a Ritonavir |2 NLM | |
| 650 | 7 | |a O3J8G9O825 |2 NLM | |
| 700 | 1 | |a Oladokun, Regina |e verfasserin |4 aut | |
| 700 | 1 | |a Ejeliogu, Emeka |e verfasserin |4 aut | |
| 700 | 1 | |a Oguche, Stephen |e verfasserin |4 aut | |
| 700 | 1 | |a Ogunbosi, Babatunde O |e verfasserin |4 aut | |
| 700 | 1 | |a Agbaji, Oche |e verfasserin |4 aut | |
| 700 | 1 | |a Odaibo, Georgina |e verfasserin |4 aut | |
| 700 | 1 | |a Imade, Godwin |e verfasserin |4 aut | |
| 700 | 1 | |a Olaleye, David |e verfasserin |4 aut | |
| 700 | 1 | |a Wiesner, Lubbe |e verfasserin |4 aut | |
| 700 | 1 | |a Darin, Kristin M |e verfasserin |4 aut | |
| 700 | 1 | |a Okonkwo, Prosper |e verfasserin |4 aut | |
| 700 | 1 | |a Kanki, Phyllis J |e verfasserin |4 aut | |
| 700 | 1 | |a Scarsi, Kimberly K |e verfasserin |4 aut | |
| 700 | 1 | |a McIlleron, Helen M |e verfasserin |4 aut | |
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