{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T14:48:59Z","timestamp":1761490139509,"version":"3.37.3"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,12,9]],"date-time":"2016-12-09T00:00:00Z","timestamp":1481241600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Immune activation, which is characteristic of both tuberculosis (TB) and human immunodeficiency virus (HIV) infection, is associated with impaired drug metabolism. We tested the hypothesis that elevated levels of systemic immune activation among adults with HIV\/TB initiating antiretroviral therapy (ART) would be associated with impaired clearance of isoniazid.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a prospective observational study of isoniazid pharmacokinetics (PK) and systemic immune activation prior to and 1 month after ART initiation. Nonlinear mixed effects analysis was performed to measure the covariate effect of immune activation on isoniazid clearance in a model that also included N\u2010acetyltransferase\u20102 (<jats:italic>NAT\u20102<\/jats:italic>) genotype and interoccasional variability on clearance (thereby analyzing the PK data before and after ART initiation in a single model).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We enrolled 40 patients in the PK visit prior to ART, and 24 patients returned for the second visit a median of 33\u00a0days after initiating antiretroviral therapy. The isoniazid concentration data were best described by a two\u2010compartment model with first\u2010order elimination. After accounting for <jats:italic>NAT\u20102<\/jats:italic> genotype, increasing levels of CD38 and HLA\u2010DR expression on CD8+ T cells (CD38<jats:sup>+<\/jats:sup>DR<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup>) were associated with decreasing isoniazid clearance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>HIV\/TB patients with high levels of immune activation demonstrated impaired isoniazid clearance. Future efforts should determine the role of this relationship in clinical hepatotoxicity events.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13172","type":"journal-article","created":{"date-parts":[[2016,12,10]],"date-time":"2016-12-10T09:22:31Z","timestamp":1481361751000},"page":"801-811","source":"Crossref","is-referenced-by-count":17,"title":["Isoniazid clearance is impaired among human immunodeficiency virus\/tuberculosis patients with high levels of immune activation"],"prefix":"10.1111","volume":"83","author":[{"given":"Christopher","family":"Vinnard","sequence":"first","affiliation":[{"name":"Public Health Research Institute New Jersey Medical School  Newark New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shruthi","family":"Ravimohan","sequence":"additional","affiliation":[{"name":"University of Pennsylvania, Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neo","family":"Tamuhla","sequence":"additional","affiliation":[{"name":"Pennsylvania Botswana\u2010UPenn Partnership  Gaborone Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6433-1154","authenticated-orcid":false,"given":"Vijay","family":"Ivaturi","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine University of Maryland  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jotam","family":"Pasipanodya","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute Baylor University Medical Center  Dallas Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shashikant","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute Baylor University Medical Center  Dallas Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chawangwa","family":"Modongo","sequence":"additional","affiliation":[{"name":"Pennsylvania Botswana\u2010UPenn Partnership  Gaborone Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola M.","family":"Zetola","sequence":"additional","affiliation":[{"name":"Pennsylvania Botswana\u2010UPenn Partnership  Gaborone Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Drew","family":"Weissman","sequence":"additional","affiliation":[{"name":"University of Pennsylvania, Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tawanda","family":"Gumbo","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute Baylor University Medical Center  Dallas Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory P.","family":"Bisson","sequence":"additional","affiliation":[{"name":"University of Pennsylvania, Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,12,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.5.2.231"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra021844"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920007782798216"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2010.355"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.5.1733-1738.2005"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-007-0305-5"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.5588\/ijtld.11.0377"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-012-1429-9"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200206-626OC"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2006.058867"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.157.6.9711039"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199101313240503"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00042560-199710010-00003"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.qai.0000153105.42455.c2"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2007.10.002"},{"key":"e_1_2_9_17_1","first-page":"904","article-title":"Elevated levels of CD38+ CD8+ T cells in HIV infection add to the prognostic value of low CD4+ T cell levels: results of 6\u00a0years of follow\u2010up. 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