{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:55:13Z","timestamp":1789188913185,"version":"build-2803163510"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T00:00:00Z","timestamp":1498867200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The MONOD ANRS 12206 trial was designated to assess simplification of a successful lopinavir (LPV)-based antiretroviral treatment in HIV-infected children younger than 3 years of age using efavirenz (EFV; 25 mg\/kg of body weight\/day) to preserve the class of protease inhibitors for children in that age group. In this substudy, EFV concentrations were measured to check the consistency of an EFV dose of 25 mg\/kg and to compare it with the 2016 FDA recommended dose. Fifty-two children underwent blood sampling for pharmacokinetic study at 6 months and 12 months after switching to EFV. We applied a Bayesian approach to derive EFV pharmacokinetic parameters using the nonlinear mixed-effect modeling (NONMEM) program. The proportion of midinterval concentrations 12 h after drug intake (<jats:italic>C<\/jats:italic><jats:sub>12 h<\/jats:sub>) corresponding to the EFV therapeutic pharmacokinetic thresholds (1 to 4 mg\/liter) was assessed according to different dose regimens (25 mg\/kg in the MONOD study versus the 2016 FDA recommended dose). With both the 25 mg\/kg\/day dose and the 2016 FDA recommended EFV dose, simulations showed that the majority of<jats:italic>C<\/jats:italic><jats:sub>12 h<\/jats:sub>values were within the therapeutic range (62.6% versus 62.8%). However, there were more children underexposed with the 2016 FDA recommended dose (11.6% versus 1.2%). Conversely, there were more concentrations above the threshold of toxicity with the 25 mg\/kg dose (36.2% versus 25.6%), with<jats:italic>C<\/jats:italic><jats:sub>12 h<\/jats:sub>values of up to 15 mg\/liter. Only 1 of 52 children was switched back to LPV because of persistent sleeping disorders, but his<jats:italic>C<\/jats:italic><jats:sub>12 h<\/jats:sub>value was within therapeutic ranges. A high EFV dose of 25 mg\/kg per day in children under 3 years old achieved satisfactory therapeutic effective levels. However, the 2016 FDA recommended EFV dose appeared to provide more acceptable safe therapeutic profiles. (This study has been registered at ClinicalTrials.gov under identifier NCT01127204.)<\/jats:p>","DOI":"10.1128\/aac.00297-17","type":"journal-article","created":{"date-parts":[[2017,5,9]],"date-time":"2017-05-09T00:40:16Z","timestamp":1494290416000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Pharmacokinetics of Efavirenz at a High Dose of 25 Milligrams per Kilogram per Day in Children 2 to 3 Years Old"],"prefix":"10.1128","volume":"61","author":[{"given":"Claire","family":"Pressiat","sequence":"first","affiliation":[{"name":"Paris Descartes University, EA 7323, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Amorissani-Folquet","sequence":"additional","affiliation":[{"name":"Pediatric Department, Centre Hospitalier Universitaire of Cocody, Abidjan, C\u00f4te d'Ivoire"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Yonaba","sequence":"additional","affiliation":[{"name":"Pediatric Department, Centre Hospitalier Universitaire Yalgado Ou\u00e9draogo, Ouagadougou, Burkina Faso"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marc","family":"Treluyer","sequence":"additional","affiliation":[{"name":"Paris Descartes University, EA 7323, Paris, France"},{"name":"Clinical Pharmacology Department, AP-HP, Paris Centre Hospital Group, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9sir\u00e9 Lucien","family":"Dahourou","sequence":"additional","affiliation":[{"name":"MONOD Project, ANRS 12206, Centre de Recherche Internationale pour la Sant\u00e9, Ouagadougou, Burkina Faso"},{"name":"Centre Muraz, Bobo-Dioulasso, Burkina Faso"},{"name":"Inserm, Unit\u00e9 U1219, Universit\u00e9 Bordeaux, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Eboua","sequence":"additional","affiliation":[{"name":"Pediatric Department, Centre Hospitalier Universitaire de Yopougon, Abidjan, C\u00f4te d'Ivoire"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Blanche","sequence":"additional","affiliation":[{"name":"Paris Descartes University, EA 7323, Paris, France"},{"name":"Immunology Hematology Pediatric Unit, AP-HP, Necker Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Mea-Assande","sequence":"additional","affiliation":[{"name":"PACCI Programme, Site ANRS, MONOD Project, Abidjan, C\u00f4te d'Ivoire"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na\u00efm","family":"Bouazza","sequence":"additional","affiliation":[{"name":"Paris Descartes University, EA 7323, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frantz","family":"Foissac","sequence":"additional","affiliation":[{"name":"Paris Descartes University, EA 7323, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Malateste","sequence":"additional","affiliation":[{"name":"Inserm, Unit\u00e9 U1219, Universit\u00e9 Bordeaux, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Ouedraogo","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, CHU Charles de Gaulle, Universit\u00e9 de Ouagadougou, Ouagadougou, Burkina Faso"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Lui","sequence":"additional","affiliation":[{"name":"Paris Descartes University, EA 7323, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9riane","family":"Leroy","sequence":"additional","affiliation":[{"name":"Inserm, Unit\u00e9 U1027, Universit\u00e9 Paul Sabatier of Toulouse 3, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9borah","family":"Hirt","sequence":"additional","affiliation":[{"name":"Paris Descartes University, EA 7323, Paris, France"},{"name":"Clinical Pharmacology Department, AP-HP, Paris Centre Hospital Group, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Sustiva (efavirenz) product monograph","author":"Bristol-Myers Squibb Canada","year":"2012","unstructured":"Bristol-Myers Squibb Canada. 2012. 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