{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T18:35:07Z","timestamp":1775500507473,"version":"3.50.1"},"reference-count":27,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2014,1,27]],"date-time":"2014-01-27T00:00:00Z","timestamp":1390780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"},{"start":{"date-parts":[[2014,2,1]],"date-time":"2014-02-01T00:00:00Z","timestamp":1391212800000},"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":[[2014,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>We modeled nevirapine (NVP) pharmacokinetics in HIV-infected Malawian patients to assess the relationship between drug exposure and patient characteristics, genetic polymorphisms, and development of hypersensitivity reaction (HSR). One thousand one hundred seventeen patients were prospectively recruited and followed for 26 weeks with multiple or single serum samples obtained in a subset of patients for NVP quantification. Single nucleotide polymorphisms (SNPs) within<jats:italic>CYP2B6<\/jats:italic>and<jats:italic>CYP3A4<\/jats:italic>genes were typed. Nonlinear mixed effects modeling was utilized to assess the influence of patient characteristics and host genetics on NVP apparent oral clearance (CL\/F) and to explore the relationship between NVP CL\/F and HSR. Published haplotype distributions were used to simulate NVP concentrations in Caucasians versus Africans. One hundred eighty patients (101 female) were included in the model; 25 experienced HSR. No associations between patient demographics or HSR and NVP CL\/F were evident. A significant relationship between<jats:italic>CYP2B6<\/jats:italic>c.983T&gt;C and<jats:italic>CYP2B6<\/jats:italic>c.516G&gt;T and NVP CL\/F was observed (<jats:italic>P<\/jats:italic>&lt; 0.01). NVP CL\/F was reduced by 23% and 36% in patients with<jats:italic>CYP2B6<\/jats:italic>983TT\/516TT and 983TC\/516GG or GT, respectively, compared to the reference genotype. Simulated exposures suggested similar proportions (13 to 17%) of patients with subtherapeutic NVP among Caucasians and an African population. Influence of<jats:italic>CYP2B6<\/jats:italic>polymorphisms on NVP CL\/F in this population is in agreement with other reports. Our data indicate a lack of association between NVP exposure and HSR. Based on these data, dose optimization based solely on ethnicity (without individual gene testing) is unlikely to impact on risk of treatment failure or toxicity even in an African population with high carriage of poor metabolizer mutations.<\/jats:p>","DOI":"10.1128\/aac.02069-13","type":"journal-article","created":{"date-parts":[[2013,11,12]],"date-time":"2013-11-12T04:30:35Z","timestamp":1384230635000},"page":"706-712","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Population Pharmacokinetic and Pharmacogenetic Analysis of Nevirapine in Hypersensitive and Tolerant HIV-Infected Patients from Malawi"],"prefix":"10.1128","volume":"58","author":[{"given":"Laura","family":"Dickinson","sequence":"first","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masautso","family":"Chaponda","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom"},{"name":"Department of Medicine, College of Medicine, University of Malawi, Blantyre, Malawi"},{"name":"Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel F.","family":"Carr","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joep J.","family":"van Oosterhout","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, University of Malawi, Blantyre, Malawi"},{"name":"Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi"},{"name":"Dignitas International, Zomba, Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johnstone","family":"Kumwenda","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, University of Malawi, Blantyre, Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David G.","family":"Lalloo","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Munir","family":"Pirmohamed","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert S.","family":"Heyderman","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saye H.","family":"Khoo","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Progress report 2011","author":"World Health Organization","year":"2011","unstructured":"World Health Organization. 2011. Global HIV\/AIDS response: epidemic update and health sector progress towards universal access. Progress report 2011. World Health Organization, Geneva, Switzerland. http:\/\/www.who.int\/hiv\/pub\/progress_report2011\/en\/index.html. Accessed 21 May 2013."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3282f4a0ed"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/528861"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1177\/135965350501000114","article-title":"Nevirapine and efavirenz pharmacokinetics and covariate analysis in the 2NN study","volume":"10","author":"Kappelhoff BS","year":"2005","unstructured":"KappelhoffBSvan LethFMacGregorTRLangeJBeijnenJHHuitemaAD. 2005. Nevirapine and efavirenz pharmacokinetics and covariate analysis in the 2NN study. Antivir. Ther. 10:145\u2013155.","journal-title":"Antivir. 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