{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:56:42Z","timestamp":1762869402997,"version":"3.41.2"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["K23AI125122 R21AI150347 to H.E.R."],"award-info":[{"award-number":["K23AI125122 R21AI150347 to H.E.R."]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007301","name":"Harvard University Center for AIDS Research","doi-asserted-by":"crossref","award":["P30 AI060354 to H.E.R."],"award-info":[{"award-number":["P30 AI060354 to H.E.R."]}],"id":[{"id":"10.13039\/100007301","id-type":"DOI","asserted-by":"crossref"}]},{"name":"U.S. President's Emergency Plan for AIDS Relief","award":["U51HA02522 U2GGH002098"],"award-info":[{"award-number":["U51HA02522 U2GGH002098"]}]},{"name":"HHS | National Institutes of Health","award":["R01 HD058972-01"],"award-info":[{"award-number":["R01 HD058972-01"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,8,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              In adults requiring protease inhibitor (PI)-based antiretroviral therapy (ART), replacing rifampicin with rifabutin is a preferred option, but there is lack of evidence to guide rifabutin dosing in children, especially with PIs. We aimed to characterize the population pharmacokinetics of rifabutin and 25-O-desacetyl rifabutin (des-rifabutin) in children and optimize its dose. We included children from three age cohorts: (i) &lt;1-year-old cohort and (ii) 1- to 3-year-old cohort, who were ART na\u00efve and received 15- to 20-mg\/kg\/day rifabutin for 2 weeks followed by lopinavir\/ritonavir (LPV\/r)-based ART with 5.0- or 2.5 mg\/kg\/day rifabutin, respectively, while the (iii) &gt;3-year-old cohort was ART-experienced and received 2.5-mg\/kg\/day rifabutin with LPV\/r-based ART. Non-linear mixed-effects modeling was used to interpret the data. Monte Carlo simulations were performed to evaluate the study doses and optimize dosing using harmonized weight bands. Twenty-eight children were included, with a median age of 10 (range 0.67\u201315.0) years, a median weight of 11 (range 4.5\u201345) kg, and a median weight-for-age\n              <jats:italic>z<\/jats:italic>\n              score of \u22123.33 (range \u22125.15 to \u22121.32). A two-compartment disposition model, scaled allometrically by weight, was developed for rifabutin and des-rifabutin. LPV\/r increased rifabutin bioavailability by 158% (95% confidence interval: 93.2%\u2013246.0%) and reduced des-rifabutin clearance by 76.6% (74.4%\u201378.3%). Severely underweight children showed 26% (17.9%\u201333.7%) lower bioavailability. Compared to adult exposures, simulations resulted in higher median steady-state rifabutin and des-rifabutin exposures in 6\u201320 kg during tuberculosis-only treatment with 20 mg\/kg\/day. During LPV\/r co-treatment, the 2.5-mg\/kg\/day dose achieved similar exposures to adults, while the 5-mg\/kg\/day dose resulted in higher exposures in children &gt;7 kg. All study doses maintained a median\n              <jats:italic>C<\/jats:italic>\n              <jats:sub>max<\/jats:sub>\n              of &lt;900 \u00b5g\/L. The suggested weight-band dosing matches adult exposures consistently across weights and simplifies dosing.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00354-24","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T13:00:26Z","timestamp":1721653226000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Population pharmacokinetics of rifabutin among HIV\/TB co-infected children on lopinavir\/ritonavir-based antiretroviral therapy"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5483-093X","authenticated-orcid":true,"given":"Manna","family":"Semere Gebreyesus","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roeland E.","family":"Wasmann","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0982-6226","authenticated-orcid":true,"given":"Helen","family":"McIlleron","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"Oladokun","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Clinical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6822-9344","authenticated-orcid":true,"given":"Prosper","family":"Okonkwo","sequence":"additional","affiliation":[{"name":"APIN Public Health Initiatives (APIN), Abuja, Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7494-079X","authenticated-orcid":true,"given":"Paolo","family":"Denti","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3599-1468","authenticated-orcid":true,"given":"Holly E.","family":"Rawizza","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA"},{"name":"Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","unstructured":"World Health Organization. 2022. Global tuberculosis report. Available from: https:\/\/www.who.int\/teams\/global-tuberculosis-programme\/tb-reports\/global-tuberculosis-report-2022\/tb-disease-burden\/2-2-tb-mortality"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jpids\/piac060"},{"key":"e_1_3_5_4_2","unstructured":"Clinton Health Acess Initiative (CHAI). 2023. HIV market report [Internet]. Available from: https:\/\/www.clintonhealthaccess.org\/report\/2023-hiv-market-report-the-state-of-hiv-market-in-low-and-middle-income-countries\/"},{"key":"e_1_3_5_5_2","unstructured":"World Health Organization. 2021. Consolidated guidelines on HIV prevention testing treatment sevice delivery and monitoring: recommendations for a public health approach. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789240031593"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01598-10"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp263"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks218"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/606056"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/2050-6511-15-61"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084866"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2011.08.003"},{"key":"e_1_3_5_13_2","unstructured":"Department of Health and Human Services. Panel on antiretroviral guidelines for adults and adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Available from: https:\/\/clinicalinfo.hiv.gov\/en\/guidelines\/hiv-clinical-guidelines-adult-and-adolescent-arv\/drug-interactions-protease-inhibitors. Retrieved 2929 SepSeptember 2023. Accessed 2929 SepSeptember 2023"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2023.05.002"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw024"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dku382"},{"key":"e_1_3_5_17_2","unstructured":"WHO. 2016. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. Geneva Switzerland. Available from: https:\/\/www.who.int\/publications\/i\/item\/9789241549684. Retrieved 3 Oct 2023."},{"key":"e_1_3_5_18_2","unstructured":"Department of Health and Human Services. Panel on opportunistic infections in children with and exposed to HIV. Guidelines for the prevention and treatment of opportunistic infections in children with and exposed to HIV. Available from: https:\/\/clinicalinfo.hiv.gov\/en\/guidelines\/hiv-clinical-guidelines-pediatric-opportunistic-infections\/whats-new-guidelines. Retrieved 99 MarMarch 2023. Accessed 99 MarMarch 2023"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa512"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.24.25"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.23574"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajhp\/56.4.333"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.24"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-015-9459-4"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-008-9088-2"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1023\/a:1012299115260"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9592.2010.03364.x"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008030287"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-011-9255-z"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-017-9542-0"},{"key":"e_1_3_5_32_2","volume-title":"Conference of Retroviruses and Opportunistic Infections (CROI)","author":"Waalewijn H","year":"2024","unstructured":"Waalewijn H, Almett, M, Wasmann RE, Cressey TR, Easterbrook P, Olumese PE, Hesseling, AC, Tarning J, Turkova, A, Svensson E, Colbers A, Were WM, Denti P, Penazzato M. 2024. Simplifying dosing by harmonizing weight-band-based dosing across therapeutic areas in children. 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