{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T01:27:43Z","timestamp":1755221263672,"version":"3.43.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T00:00:00Z","timestamp":1686528000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n            <jats:title>Objective<\/jats:title>\n            <jats:p>In AIDS Clinical Trials Group study A5375, a pharmacokinetic trial of levonorgestrel emergency contraception, double-dose levonorgestrel (3\u2005mg, versus standard dose 1.5\u2005mg) offset the induction effects of efavirenz or rifampin on plasma levonorgestrel exposure over 8\u2005h post-dose (AUC<jats:sub>0-8h<\/jats:sub>). We characterized the pharmacogenetics of these interactions.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Cisgender women receiving efavirenz- or dolutegravir-based HIV therapy, or on isoniazid-rifampin for tuberculosis, were followed after a single oral dose of levonorgestrel. Linear regression models, adjusted for BMI and age, characterized associations of <jats:italic toggle=\"yes\">CYP2B6<\/jats:italic> and <jats:italic toggle=\"yes\">NAT2<\/jats:italic> genotypes (which affect plasma efavirenz and isoniazid exposure, respectively) with levonorgestrel pharmacokinetic parameters.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Of 118 evaluable participants, 17 received efavirenz\/levonorgestrel 1.5\u2005mg, 35 efavirenz\/levonorgestrel 3\u2005mg, 34 isoniazid-rifampin\/levonorgestrel 3\u2005mg, and 32 (control group) dolutegravir\/levonorgestrel 1.5\u2005mg. There were 73 Black and 33 Asian participants. Regardless of genotype, women on efavirenz and isoniazid-rifampin had higher levonorgestrel clearance. In the efavirenz\/levonorgestrel 3\u2005mg group, <jats:italic toggle=\"yes\">CYP2B6<\/jats:italic> normal\/intermediate metabolizers had levonorgestrel AUC<jats:sub>0-8h<\/jats:sub> values similar to controls, while <jats:italic toggle=\"yes\">CYP2B6<\/jats:italic> poor metabolizers had AUC<jats:sub>0-8h<\/jats:sub> values of 40% lower than controls. In the isoniazid-rifampin group, <jats:italic toggle=\"yes\">NAT2<\/jats:italic> rapid\/intermediate acetylators had levonorgestrel AUC<jats:sub>0-8h<\/jats:sub> values similar to controls, while <jats:italic toggle=\"yes\">NAT2<\/jats:italic> slow acetylators had AUC<jats:sub>0-8h<\/jats:sub> values 36% higher than controls.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>\n                                 <jats:italic toggle=\"yes\">CYP2B6<\/jats:italic> poor metabolizer genotypes exacerbate the efavirenz-levonorgestrel interaction, likely by increased CYP3A induction with higher efavirenz exposure, making the interaction more difficult to overcome. <jats:italic toggle=\"yes\">NAT2<\/jats:italic> slow acetylator genotypes attenuate the rifampin-levonorgestrel interaction, likely by increased CYP3A inhibition with higher isoniazid exposure.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/fpc.0000000000000501","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T09:00:08Z","timestamp":1686560408000},"page":"126-135","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacogenetic interactions of efavirenz or rifampin and isoniazid with levonorgestrel emergency contraception during treatment of HIV or tuberculosis"],"prefix":"10.1097","volume":"33","author":[{"given":"Nana","family":"Agyemang","sequence":"first","affiliation":[{"name":"Tufts University School of Medicine, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly K.","family":"Scarsi","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paxton","family":"Baker","sequence":"additional","affiliation":[{"name":"Vanderbilt Technologies for Advanced Genomics, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura M.","family":"Smeaton","sequence":"additional","affiliation":[{"name":"Center for Biostatistics in AIDS Research, Harvard TH Chan School of Public Health; Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony T.","family":"Podany","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxine","family":"Olefsky","sequence":"additional","affiliation":[{"name":"Center for Biostatistics in AIDS Research, Harvard TH Chan School of Public Health; Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Woolley","sequence":"additional","affiliation":[{"name":"DLH Corporation, Silver Spring"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Barr","sequence":"additional","affiliation":[{"name":"Office of Research on Women\u2019s Health, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Pham","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sajeeda","family":"Mawlana","sequence":"additional","affiliation":[{"name":"Enhancing Care Foundation, Wentworth Hospital, Durban, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khuanchai","family":"Supparatpinyo","sequence":"additional","affiliation":[{"name":"Chiang Mai University, Chiang Mai"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sivaporn","family":"Gatechompol","sequence":"additional","affiliation":[{"name":"HIV-NAT, Thai Red Cross AIDS Research Center, Bangkok, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilia M.","family":"Jalil","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Gadama","sequence":"additional","affiliation":[{"name":"Johns Hopkins Research Project, Blantyre, Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharlaa","family":"Badal-Faesen","sequence":"additional","affiliation":[{"name":"Clinical HIV Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marije","family":"Van Schalkwyk","sequence":"additional","affiliation":[{"name":"Family Center for Research with Ubuntu, Division of Infectious Diseases, Department of Medicine, Stellenbosch University, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecelia","family":"Kayama","sequence":"additional","affiliation":[{"name":"University of North Carolina Project-Malawi, Lilongwe, Malawi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo F.","family":"Belaunzaran-Zamudio","sequence":"additional","affiliation":[{"name":"Contractor, Division of AIDS, National Institute of Allergy and Infectious DiseasesBethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Godfrey","sequence":"additional","affiliation":[{"name":"Office of the Global AIDS Coordinator, Department of State, Washington, DC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan E.","family":"Cohn","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosie","family":"Mngqibisa","sequence":"additional","affiliation":[{"name":"Enhancing Care Foundation, Wentworth Hospital, Durban, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Haas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University School of Medicine"},{"name":"Department of Internal Medicine, Meharry Medical College, Nashville, Tennessee, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the AIDS Clinical Trials Group A5375 Study 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