@article{Rawizza2020,
abstract = {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 AUC 0-24 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 AUC 0-24 was 5.21 (4.38-6.60) lg{\'{A}}h/mL. Four participants had AUC 0-24 below 3.8 lg{\'{A}}h/mL (a target for the population average exposure) at week 2 and all had AUC 0-24 higher than 3.8 lg{\'{A}}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 AUC 0-24 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.},
author = {Rawizza, Holly E and Oladokun, Regina and Ejeliogu, Emeka and Oguche, Stephen and Ogunbosi, Babatunde O and Agbaji, Oche and Odaibo, Georgina and Imade, Godwin and Olaleye, David and Wiesner, Lubbe and Darin, Kristin M and Okonkwo, Prosper and Kanki, Phyllis J and Scarsi, Kimberly K and McIlleron, Helen M},
doi = {10.1093/jac/dkaa512},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Rawizza et al. - 2021 - Rifabutin pharmacokinetics and safety among TBHIV-coinfected children receiving lopinavirritonavir-containing se.pdf:pdf},
issn = {0305-7453},
journal = {Journal of Antimicrobial Chemotherapy},
keywords = {OA,OA{\_}PMC,child,fund{\_}not{\_}ack,hiv,lopinavir,original,pharmacokinetics,rifabutin,ritonavir,safety,tuberculosis},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}not{\_}ack,original},
month = {dec},
number = {3},
pages = {710--717},
pmid = {33294914},
publisher = {Oxford University Press (OUP)},
title = {{Rifabutin pharmacokinetics and safety among TB/HIV-coinfected children receiving lopinavir/ritonavir-containing second-line ART}},
url = {https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkaa512/6028468},
volume = {76},
year = {2021}
}

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The AUC 0-24 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 AUC 0-24 was 5.21 (4.38-6.60) lgÁh/mL. Four participants had AUC 0-24 below 3.8 lgÁh/mL (a target for the population average exposure) at week 2 and all had AUC 0-24 higher than 3.8 lgÁh/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 AUC 0-24 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.","author":[{"propositions":[],"lastnames":["Rawizza"],"firstnames":["Holly","E"],"suffixes":[]},{"propositions":[],"lastnames":["Oladokun"],"firstnames":["Regina"],"suffixes":[]},{"propositions":[],"lastnames":["Ejeliogu"],"firstnames":["Emeka"],"suffixes":[]},{"propositions":[],"lastnames":["Oguche"],"firstnames":["Stephen"],"suffixes":[]},{"propositions":[],"lastnames":["Ogunbosi"],"firstnames":["Babatunde","O"],"suffixes":[]},{"propositions":[],"lastnames":["Agbaji"],"firstnames":["Oche"],"suffixes":[]},{"propositions":[],"lastnames":["Odaibo"],"firstnames":["Georgina"],"suffixes":[]},{"propositions":[],"lastnames":["Imade"],"firstnames":["Godwin"],"suffixes":[]},{"propositions":[],"lastnames":["Olaleye"],"firstnames":["David"],"suffixes":[]},{"propositions":[],"lastnames":["Wiesner"],"firstnames":["Lubbe"],"suffixes":[]},{"propositions":[],"lastnames":["Darin"],"firstnames":["Kristin","M"],"suffixes":[]},{"propositions":[],"lastnames":["Okonkwo"],"firstnames":["Prosper"],"suffixes":[]},{"propositions":[],"lastnames":["Kanki"],"firstnames":["Phyllis","J"],"suffixes":[]},{"propositions":[],"lastnames":["Scarsi"],"firstnames":["Kimberly","K"],"suffixes":[]},{"propositions":[],"lastnames":["McIlleron"],"firstnames":["Helen","M"],"suffixes":[]}],"doi":"10.1093/jac/dkaa512","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Rawizza et al. - 2021 - Rifabutin pharmacokinetics and safety among TBHIV-coinfected children receiving lopinavirritonavir-containing se.pdf:pdf","issn":"0305-7453","journal":"Journal of Antimicrobial Chemotherapy","keywords":"OA,OA_PMC,child,fund_not_ack,hiv,lopinavir,original,pharmacokinetics,rifabutin,ritonavir,safety,tuberculosis","mendeley-tags":"OA,OA_PMC,fund_not_ack,original","month":"dec","number":"3","pages":"710–717","pmid":"33294914","publisher":"Oxford University Press (OUP)","title":"Rifabutin pharmacokinetics and safety among TB/HIV-coinfected children receiving lopinavir/ritonavir-containing second-line ART","url":"https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkaa512/6028468","volume":"76","year":"2021","bibtex":"@article{Rawizza2020,\r\nabstract = {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 AUC 0-24 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 AUC 0-24 was 5.21 (4.38-6.60) lg{\\'{A}}h/mL. Four participants had AUC 0-24 below 3.8 lg{\\'{A}}h/mL (a target for the population average exposure) at week 2 and all had AUC 0-24 higher than 3.8 lg{\\'{A}}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 AUC 0-24 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.},\r\nauthor = {Rawizza, Holly E and Oladokun, Regina and Ejeliogu, Emeka and Oguche, Stephen and Ogunbosi, Babatunde O and Agbaji, Oche and Odaibo, Georgina and Imade, Godwin and Olaleye, David and Wiesner, Lubbe and Darin, Kristin M and Okonkwo, Prosper and Kanki, Phyllis J and Scarsi, Kimberly K and McIlleron, Helen M},\r\ndoi = {10.1093/jac/dkaa512},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Rawizza et al. - 2021 - Rifabutin pharmacokinetics and safety among TBHIV-coinfected children receiving lopinavirritonavir-containing se.pdf:pdf},\r\nissn = {0305-7453},\r\njournal = {Journal of Antimicrobial Chemotherapy},\r\nkeywords = {OA,OA{\\_}PMC,child,fund{\\_}not{\\_}ack,hiv,lopinavir,original,pharmacokinetics,rifabutin,ritonavir,safety,tuberculosis},\r\nmendeley-tags = {OA,OA{\\_}PMC,fund{\\_}not{\\_}ack,original},\r\nmonth = {dec},\r\nnumber = {3},\r\npages = {710--717},\r\npmid = {33294914},\r\npublisher = {Oxford University Press (OUP)},\r\ntitle = {{Rifabutin pharmacokinetics and safety among TB/HIV-coinfected children receiving lopinavir/ritonavir-containing second-line ART}},\r\nurl = {https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkaa512/6028468},\r\nvolume = {76},\r\nyear = {2021}\r\n}\r\n","author_short":["Rawizza, H. 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