{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:01:13Z","timestamp":1790805673090,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T00:00:00Z","timestamp":1607472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007301","name":"Harvard University Center for AIDS Research","doi-asserted-by":"publisher","award":["P30 AI060354"],"award-info":[{"award-number":["P30 AI060354"]}],"id":[{"id":"10.13039\/100007301","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K23AI125122"],"award-info":[{"award-number":["K23AI125122"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cooperative Agreement","award":["U51HA02522"],"award-info":[{"award-number":["U51HA02522"]}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206379\/Z\/17\/Z"],"award-info":[{"award-number":["206379\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"publisher","award":["UM1AI068634"],"award-info":[{"award-number":["UM1AI068634"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"publisher","award":["UM1AI068636"],"award-info":[{"award-number":["UM1AI068636"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"publisher","award":["UM1AI106701"],"award-info":[{"award-number":["UM1AI106701"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Maternal Pediatric Adolescent AIDS Clinical Trials Group","award":["U01 AI068632"],"award-info":[{"award-number":["U01 AI068632"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We evaluated rifabutin safety and plasma pharmacokinetics among coinfected children 3\u201315\u2009years of age receiving rifabutin 2.5\u2009mg\/kg daily with standard doses of lopinavir\/ritonavir. The AUC0\u201324 at 2, 4 and 8\u2009weeks 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among 15 children with median (IQR) age 13.1 (10.9\u201314.0) years and weight 25.5 (22.3\u201330.5) kg, the median (IQR) rifabutin AUC0\u201324 was 5.21 (4.38\u20136.60) \u03bcg\u00b7h\/mL. Four participants had AUC0\u201324 below 3.8\u2009\u03bcg\u00b7h\/mL (a target for the population average exposure) at week 2 and all had AUC0\u201324 higher than 3.8\u2009\u03bcg\u00b7h\/mL at the 4 and 8\u2009week 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\u2009=\u20094) and grade 4 (n\u2009=\u20091) neutropenia resolved without treatment interruption or clinical sequelae in all patients. One child died at week 4 of HIV-related complications.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In children, rifabutin 2.5\u2009mg\/kg daily achieved AUC0\u201324 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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaa512","type":"journal-article","created":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T04:33:54Z","timestamp":1606278834000},"page":"710-717","source":"Crossref","is-referenced-by-count":5,"title":["Rifabutin pharmacokinetics and safety among TB\/HIV-coinfected children receiving lopinavir\/ritonavir-containing second-line ART"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3599-1468","authenticated-orcid":false,"given":"Holly E","family":"Rawizza","sequence":"first","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Boston, MA, USA"},{"name":"Harvard T.H. Chan School of Public Health, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Oladokun","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emeka","family":"Ejeliogu","sequence":"additional","affiliation":[{"name":"College of Health Sciences, Jos University Teaching Hospital, University of Jos, Jos, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Oguche","sequence":"additional","affiliation":[{"name":"College of Health Sciences, Jos University Teaching Hospital, University of Jos, Jos, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babatunde O","family":"Ogunbosi","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oche","family":"Agbaji","sequence":"additional","affiliation":[{"name":"College of Health Sciences, Jos University Teaching Hospital, University of Jos, Jos, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina","family":"Odaibo","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Godwin","family":"Imade","sequence":"additional","affiliation":[{"name":"College of Health Sciences, Jos University Teaching Hospital, University of Jos, Jos, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Olaleye","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Ibadan, University College Hospital, Ibadan, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9070-8699","authenticated-orcid":false,"given":"Lubbe","family":"Wiesner","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin M","family":"Darin","sequence":"additional","affiliation":[{"name":"Northwestern University School of Professional Studies, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prosper","family":"Okonkwo","sequence":"additional","affiliation":[{"name":"APIN Public Health Initiatives Ltd\/Gte, Abuja, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phyllis J","family":"Kanki","sequence":"additional","affiliation":[{"name":"Harvard T.H. Chan School of Public Health, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly K","family":"Scarsi","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen M","family":"McIlleron","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,9]]},"reference":[{"key":"2021021208585080500_dkaa512-B1","year":"2019"},{"key":"2021021208585080500_dkaa512-B2","doi-asserted-by":"crossref","first-page":"e438\u201344","DOI":"10.1016\/S2352-3018(15)00137-X","article-title":"Causes of hospital admission among people living with HIV worldwide: a systematic review and meta-analysis","volume":"2","author":"Ford","year":"2015","journal-title":"Lancet HIV"},{"key":"2021021208585080500_dkaa512-B3","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.5588\/ijtld.13.0030","article-title":"Risk factors for mortality in Malawian children with human immunodeficiency virus and tuberculosis co-infection","volume":"17","author":"Buck","year":"2013","journal-title":"Int J Tuberc Lung Dis"},{"key":"2021021208585080500_dkaa512-B4","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S1473-3099(16)30474-1","article-title":"Mortality in children diagnosed with tuberculosis: a systematic review and meta-analysis","volume":"17","author":"Jenkins","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"2021021208585080500_dkaa512-B5","year":"2016","edition":"Second Edition"},{"key":"2021021208585080500_dkaa512-B6","year":"2018"},{"key":"2021021208585080500_dkaa512-B7","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1128\/AAC.48.5.1553-1560.2004","article-title":"Pharmacokinetics of adjusted-dose lopinavir-ritonavir combined with rifampin in healthy volunteers","volume":"48","author":"La Porte","year":"2004","journal-title":". 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