{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T06:09:07Z","timestamp":1789366147594,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2017,9,20]],"date-time":"2017-09-20T00:00:00Z","timestamp":1505865600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>A clinical study was conduct in HIV\u2010infected children to evaluate the prophylactic doses of cotrimoxazole [sulfamethoxazole (SMX) and trimethoprim (TMP)] advised by the WHO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Children received lopinavir\u2010based antiretroviral therapy with cotrimoxazole prophylaxis (200\u00a0mg of SMX\/40\u00a0mg of TMP once daily). A nonlinear mixed effects modelling approach was used to analyse plasma concentrations. Factors that could impact the pharmacokinetic profile were investigated. The model was subsequently used to simulate individual exposure and evaluate different administration schemes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The cohort comprised 136 children [average age: 1.9 years (range: [0.7\u20134]), average weight: 9.5\u00a0kg (range: [6\u201316.3])]. A dose per kg was justified by the significant influence of implementing an allometrically scaled body size covariate on SMX and TMP pharmacokinetics. SMX and TPM clearance were estimated at 0.49\u00a0l\u00a0h<jats:sup>\u22121<\/jats:sup>\/9.5\u00a0kg and 3.06\u00a0l\u00a0h<jats:sup>\u22121<\/jats:sup>\/9.5\u00a0kg, respectively. The simulated exposures obtained after administration of oral dosing recommended by the WHO for children from 10 to 15\u00a0kg were significantly lower than in adults for SMX and TMP. This could induce a reduction of effectiveness of cotrimoxazole. Simulations show that regimens of 30\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>of SMX and 6\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>of TMP in the 5\u201310\u00a0kg group and 25\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>of SMX and 5\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>of TMP in the 10\u201315\u00a0kg group are more suitable doses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this context of high prevalence of opportunistic infections, a lower exposure to cotrimoxazole in children than adults was noted. To achieve comparable exposure to adults, a dosing scheme per kg was proposed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13397","type":"journal-article","created":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T19:52:38Z","timestamp":1502481158000},"page":"2729-2740","source":"Crossref","is-referenced-by-count":5,"title":["Suboptimal cotrimoxazole prophylactic concentrations in HIV\u2010infected children according to the WHO guidelines"],"prefix":"10.1111","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0728-2701","authenticated-orcid":false,"given":"Claire","family":"Pressiat","sequence":"first","affiliation":[{"name":"Paris Descartes University, EA 7323 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique","family":"Mea\u2010Assande","sequence":"additional","affiliation":[{"name":"PACCI Programme, Site ANRS, MONOD Project 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\u2010Marc","family":"Treluyer","sequence":"additional","affiliation":[{"name":"Paris Descartes University, EA 7323 Paris France"},{"name":"Clinical Pharmacology Department AP\u2010HP, Paris Centre Hospital Group Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9sir\u00e9\u2010Lucien","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\u2010Dioulasso Burkina Faso"},{"name":"Inserm, Unit\u00e9 U1219 Universit\u00e9 Bordeaux Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Amorissani\u2010Folquet","sequence":"additional","affiliation":[{"name":"Pediatric Department Centre Hospitalier Universitaire of Cocody 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\u2010HP, Necker Hospital Paris 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":"Diarra","family":"Ye","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":"Karen","family":"Malateste","sequence":"additional","affiliation":[{"name":"Inserm, Unit\u00e9 U1219 Universit\u00e9 Bordeaux Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Paris Descartes University, EA 7323 Paris France"},{"name":"Clinical Pharmacology Department AP\u2010HP, Paris Centre Hospital Group Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeriane","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\u2010HP, Paris Centre Hospital Group Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the MONOD Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200406002-00004"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17140-7"},{"key":"e_1_2_9_4_1","unstructured":"World Health Organisation.Guideline on when to start antiretroviral therapy and on pre\u2010exposure prophylaxis for HIV. 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