{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T07:15:47Z","timestamp":1782544547842,"version":"3.54.5"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec>\n            <jats:title>Objectives<\/jats:title>\n            <jats:p>The effect of rifapentine plus isoniazid on efavirenz pharmacokinetics was characterized in AIDS Clinical Trials Group protocol A5279 (NCT01404312). The present analyses characterize pharmacogenetic interactions between these drugs, and with nevirapine.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>A subset of HIV-positive individuals receiving efavirenz- or nevirapine-containing antiretroviral therapy in A5279 underwent pharmacokinetic evaluations at baseline, and again weeks 2 and 4 after initiating daily rifapentine plus isoniazid. Associations with polymorphisms relevant to efavirenz, nevirapine, isoniazid, and rifapentine pharmacokinetics were assessed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Of 128 participants, 101 were evaluable for associations with rifapentine and its active 25-desacetyl metabolite, 87 with efavirenz, and 38 with nevirapine. In multivariable analyses, <jats:italic toggle=\"yes\">NAT2<\/jats:italic> slow acetylators had greater week 4 plasma concentrations of rifapentine (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20092.6\u2009\u00d7\u200910<jats:sup>\u22123<\/jats:sup>) and 25-desacetyl rifapentine (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009=\u20097.0\u2009\u00d7\u200910<jats:sup>\u22125<\/jats:sup>) among all participants, and in efavirenz and nevirapine subgroups. <jats:italic toggle=\"yes\">NAT2<\/jats:italic> slow acetylators also had greater plasma efavirenz and nevirapine concentration increases from baseline to week 4, and greater decreases from baseline in clearance. <jats:italic toggle=\"yes\">CYP2B6<\/jats:italic> poor metabolizers had greater efavirenz concentrations at all weeks and greater nevirapine concentrations at baseline. None of 47 additional polymorphisms in 11 genes were significantly associated with pharmacokinetics.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Among HIV-positive individuals receiving efavirenz or nevirapine, and who then initiated rifapentine plus isoniazid in A5279, <jats:italic toggle=\"yes\">NAT2<\/jats:italic> slow acetylators had greater rifapentine and 25-desacetyl rifapentine concentrations, and greater increases from baseline in plasma efavirenz and nevirapine concentrations. These associations are likely mediated by greater isoniazid exposure in <jats:italic toggle=\"yes\">NAT2<\/jats:italic> slow acetylators.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/fpc.0000000000000417","type":"journal-article","created":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T10:50:20Z","timestamp":1597834220000},"page":"17-27","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":12,"title":["Pharmacogenetic interactions of rifapentine plus isoniazid with efavirenz or nevirapine"],"prefix":"10.1097","volume":"31","author":[{"given":"David W.","family":"Haas","sequence":"first","affiliation":[{"name":"Department of Medicine, Vanderbilt University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony T.","family":"Podany","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Science, Antiviral Pharmacology Laboratory, UNMC Center for Drug Discovery, University of Nebraska Medical Center, Omaha"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Bao","sequence":"additional","affiliation":[{"name":"Statistical and Data Analysis Center, Harvard T.H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Swindells","sequence":"additional","affiliation":[{"name":"Infectious Diseases, Internal Medicine, University of Nebraska Medical Center, Omaha"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Chaisson","sequence":"additional","affiliation":[{"name":"Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noluthando","family":"Mwelase","sequence":"additional","affiliation":[{"name":"Helen Joseph Hospital, University of Witwatersrand University, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khuanchai","family":"Supparatpinyo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Research Institute for Health Sciences and Faculty of Medicine, Chiang Mai University, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lerato","family":"Mohapi","sequence":"additional","affiliation":[{"name":"Perinatal HIV Research Unit, University of the Witwatersrand and Chris Hani Baragwanath Hospital, Soweto, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amita","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Medicine, Center for Clinical Global Health Education, Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constance A.","family":"Benson","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Global Public Health, Antiviral Research Center, University of California, San Diego"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paxton","family":"Baker","sequence":"additional","affiliation":[{"name":"Vanderbilt Technologies for Advanced Genomics, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney V.","family":"Fletcher","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Science, Antiviral Pharmacology Laboratory, UNMC Center for Drug Discovery, University of Nebraska Medical Center, Omaha; for the AIDS Clinical Trials Group A5279 Study Team"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2020,8,17]]},"reference":[{"key":"R2-20250812","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1378\/chest.09-0394","article-title":"Latent TB infection treatment acceptance and completion in the United States and Canada.","volume":"137","author":"Horsburgh","year":"2010","journal-title":"Chest"},{"key":"R3-20250812","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1056\/NEJMoa1104875","article-title":"Three months of rifapentine and isoniazid for latent 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