{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:29:09Z","timestamp":1791347349039,"version":"4.3.1"},"reference-count":49,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rifampicin-based tuberculosis (TB) treatment alters efavirenz (EFV) clearance. Polymorphisms in important drug metabolizing enzymes and the implications for EFV dosing were investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Trough EFV concentrations (C were measured m\n                      <jats:sub>in<\/jats:sub>\n                      ) in 54 South African black patients. During TB treatment, EFV dose was 600 mg in patients &lt;50 kg or 800 mg if \u226550 kg. Off TB treatment it was 600 mg. Polymorphisms in CYP2B6, CYP2A6 and UGT2B7 enzymes were sequenced. A multivariate generalized estimating equations model was fitted to assess predictors of high median EFV C. m\n                      <jats:sub>in<\/jats:sub>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During TB treatment, median EFV C was 3.2 m\n                      <jats:sub>in<\/jats:sub>\n                      (IQR 2.6\u20136.3) \u03bcg\/ml and 3.3 (2.4-9.5) \u03bcg\/ml in the 800 mg and 600 mg groups, respectively. After TB treatment EFV C was 2.0 (1.4-3.5) \u03bcg\/ml. Minor allele m\n                      <jats:sub>in<\/jats:sub>\n                      frequencies for CYP2B6 516G\u2192T, 785A\u2192G, 983T\u2192C, UGT2B7-372G\u2192A, CYP2A6*9B and CYP2A6*17 were 0.31, 0.33, 0.23, 0.29, 0.10 and 0.02, respectively. Haplotypes CYP2B6*6 and CYP2B6*18 were found in 38.9% and 25.9% of patients, respectively. Polymorphisms in all three CYP2B6 genes studied (516T-785G-983C) were present in 11.1% of patients and in this group median EFV C\n                      <jats:sub>min<\/jats:sub>\n                      was 19.2 (IQR 9.5\u201320) \u03bcg\/ml during and 4.7 (IQR 3.5\u20135.6) \u03bcg\/ml after TB treatment. The presence of TB treatment and composite genotypes CYP2B6 516 GT\/TT, CYP2B6 983 TC\/CC and CYP2A6*9B carrier status predicted median EFV C\n                      <jats:sub>min<\/jats:sub>\n                      &gt;4 \u03bcg\/ml. Adverse events due to high EFV concentrations were rare.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Because polymorphisms of EFV metabolizing enzymes are frequent and are associated with elevated EFV concentrations in this population, EFV dose increases are unnecessary when concomitant rifampicin-containing TB treatment is prescribed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp2877","type":"journal-article","created":{"date-parts":[[2014,10,15]],"date-time":"2014-10-15T08:52:59Z","timestamp":1413363179000},"page":"297-306","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Efavirenz Dosing: Influence of Drug Metabolizing Enzyme Polymorphisms and Concurrent Tuberculosis Treatment"],"prefix":"10.1177","volume":"20","author":[{"given":"Tanuja N","family":"Gengiah","sequence":"first","affiliation":[{"name":"CAPRISA \u2013 Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia H","family":"Botha","sequence":"additional","affiliation":[{"name":"Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nonhlanhla","family":"Yende-Zuma","sequence":"additional","affiliation":[{"name":"CAPRISA \u2013 Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kogieleum","family":"Naidoo","sequence":"additional","affiliation":[{"name":"CAPRISA \u2013 Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim S Abdool","family":"Karim","sequence":"additional","affiliation":[{"name":"CAPRISA \u2013 Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa"},{"name":"Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,4,1]]},"reference":[{"key":"bibr1-IMP2877","unstructured":"Food and Drug Administration. 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