{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T15:44:48Z","timestamp":1777045488443,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite the potential for efavirenz (EFV) to be an effective alternative antiretroviral agent, its sources of wide inter\u2010 and intra\u2010individual pharmacokinetic (PK) variability are not well\u2010characterized in children. We investigated the effects of genetic and non\u2010genetic factors, including demographic, treatment duration, baseline clinical, and biochemical characteristics, on the PKs of EFV through population\u2010PK modeling. Antiretroviral therapy (ART) na\u00efve HIV infected children, 3\u201316\u2009years (<jats:italic>n<\/jats:italic>\u00a0=\u00a0100), were enrolled in Ethiopia and received EFV\u2010based combination ART. EFV concentrations after the first dose and at steady\u2010state collected over a span of 1\u2009year were modeled using population\u2010based methods. A one\u2010compartment model with first\u2010order absorption kinetics described the observed EFV data adequately. The <jats:italic>CYP2B6*6<\/jats:italic> and <jats:italic>ABCB1c.4036A&gt;G<\/jats:italic> genotypes were identified as major factors influencing EFV clearance. The typical estimates of oral clearance, volume of distribution, and absorption rate constant for typical 22\u2009kg children with <jats:italic>CYP2B6 *1\/*1<\/jats:italic> and <jats:italic>ABCB1c.4036G\/G<\/jats:italic> genotypes were 4.3\u00a0L\/h, 124\u2009L, and 0.776\/h, respectively. Clearance was reduced by 28% and 72% in <jats:italic>CYP2B6*1\/*6<\/jats:italic> and <jats:italic>CYP2B6*6\/*6<\/jats:italic> genotypes, respectively. Compared to week 1, clearance was higher from weeks 8 and 12 in <jats:italic>CYP2B6*1\/*6<\/jats:italic> and <jats:italic>CYP2B6*1\/*1<\/jats:italic> genotypes, respectively. Simulations indicated that EFV 12\u2010h concentrations were comparable across weight bands, but more than 80% of subjects with <jats:italic>CYP2B6*6\/*6<\/jats:italic> had EFV concentrations greater than 4\u00a0\u03bcg\/mL. EFV PK variability among children is partly explained by body weight, treatment duration, <jats:italic>CYP2B6*6<\/jats:italic>, and <jats:italic>ABCB<\/jats:italic>1 rs3842 genotypes. Therefore, in addition to body weight, pediatric dosing of EFV should consider pharmacogenetic variability, duration of therapy, and individual treatment outcomes.<\/jats:p>","DOI":"10.1002\/psp4.12951","type":"journal-article","created":{"date-parts":[[2023,2,25]],"date-time":"2023-02-25T07:38:30Z","timestamp":1677310710000},"page":"783-794","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic and non\u2010genetic factors influencing efavirenz population pharmacokinetics among human immunodeficiency virus\u20101\u2010infected children in Ethiopia"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3209-2731","authenticated-orcid":false,"given":"Adugna","family":"Chala","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacy, College of Health Sciences Addis Ababa University  Addis Ababa Ethiopia"},{"name":"Department of Global Public Health 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