{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T21:19:19Z","timestamp":1778879959809,"version":"3.51.4"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Tenofovir is a component of preferred combination antiretroviral therapy (ART) regimens in Africa. Few pharmacogenetic studies have been conducted on tenofovir exposure in Africa, where genetic diversity is greatest.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Objective<\/jats:title>\n            <jats:p>We characterized the pharmacogenetics of plasma tenofovir clearance in Southern Africans receiving tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Adults randomized to TAF or TDF in dolutegravir-containing arms of the ADVANCE trial (NCT03122262) were studied. Linear regression models stratified by study arm examined associations with unexplained variability in tenofovir clearance. We investigated genetic associations with polymorphisms selected <jats:italic toggle=\"yes\">a priori<\/jats:italic> followed by genome-wide associations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>A total of 268 participants (138 and 130 in the TAF and TDF arm, respectively) were evaluable for associations. Among polymorphisms previously associated with any drug-related phenotype, <jats:italic toggle=\"yes\">IFNL4<\/jats:italic> rs12979860 was associated with more rapid tenofovir clearance in both arms (TAF: <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.003; TDF: <jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20090.003). Genome-wide, the lowest <jats:italic toggle=\"yes\">P<\/jats:italic> values for tenofovir clearance in TAF and TDF arms were <jats:italic toggle=\"yes\">LINC01684<\/jats:italic> rs9305223 (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20093.0\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>) and intergenic rs142693425 (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20091.4\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>), respectively.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Among Southern Africans randomized to TAF or TDF in ADVANCE, unexplained variability in tenofovir clearance was associated with a polymorphism in <jats:italic toggle=\"yes\">IFNL4<\/jats:italic>, an immune-response gene. It is unclear how this gene would affect tenofovir disposition.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/fpc.0000000000000495","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T10:14:56Z","timestamp":1682504096000},"page":"79-87","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV"],"prefix":"10.1097","volume":"33","author":[{"given":"Zinhle","family":"Cindi","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aida N.","family":"Kawuma","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Maartens","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Bradford","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simiso","family":"Sokhela","sequence":"additional","affiliation":[{"name":"Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nomathemba","family":"Chandiwana","sequence":"additional","affiliation":[{"name":"Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willem D. Francois","family":"Venter","sequence":"additional","affiliation":[{"name":"Ezintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roeland E.","family":"Wasmann","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Denti","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lubbe","family":"Wiesner","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marylyn D.","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Department of Genetics and Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Haas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center"},{"name":"Department of Internal Medicine, Meharry Medical College, Nashville, Tennessee, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phumla","family":"Sinxadi","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2023,3,6]]},"reference":[{"key":"R4-20250808","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1080\/00498250500354493","article-title":"Multidrug 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