{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T06:21:38Z","timestamp":1790490098470,"version":"4.1.0"},"reference-count":14,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T00:00:00Z","timestamp":1562716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000278","name":"Department for International Development","doi-asserted-by":"publisher","award":["MRC MR\/M0074131\/1"],"award-info":[{"award-number":["MRC MR\/M0074131\/1"]}],"id":[{"id":"10.13039\/501100000278","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:p>The central nervous system (CNS) is a known <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content> reservoir, yet little is known about drug exposure in the brain. Our primary objective was to quantify exposure of three common antiretrovirals in brain tissue and compare exposures to plasma and cerebrospinal fluid (CSF). We also sought to identify pockets of brain most vulnerable to inadequate drug exposures and examine the role of meningitis in drug penetration into the <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>. Tenofovir, lamivudine, and efavirenz concentrations were measured using liquid chromatography and tandem mass spectrometry in plasma and <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> from 14 individuals with <jats:styled-content style=\"fixed-case\">HIV,<\/jats:styled-content> 7 with cryptococcal meningitis. In four individuals (three with meningitis) drug concentrations were also measured in 13 distinct brain tissue regions. In subjects with meningitis, geometric mean ratio (95% confidence interval) of tenofovir <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> to plasma was 66% (7\u2013598%) and 14% (6\u201331%) in subjects without meningitis. Lamivudine <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> penetration was 100% (25\u2013409%) in subjects with meningitis and 30% (24\u201337%) in subjects without meningitis. Tenofovir\u00a0brain tissue concentrations were 36% (14\u2013124%) of plasma and 49% (1\u2013572%) of <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>. Lamivudine brain concentrations were 37% (23\u201364%) of plasma and 27% (1\u2013104%) of <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>. Efavirenz brain tissue concentrations were 128% (108\u2013179%) of plasma. Tissues collected postmortem provide a unique opportunity to assess drug distribution in tissues difficult to sample in living subjects. <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> is a poor surrogate for drug exposure throughout the CNS. Antiretrovirals differentially penetrate into the CNS and penetration may be enhanced by meningitis.<\/jats:p>","DOI":"10.1111\/cts.12661","type":"journal-article","created":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T18:49:47Z","timestamp":1560797387000},"page":"445-449","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Cerebrospinal Fluid and Brain Tissue Penetration of Tenofovir, Lamivudine, and Efavirenz in Postmortem Tissues with Cryptococcal Meningitis"],"prefix":"10.1111","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5513-5509","authenticated-orcid":false,"given":"Melanie R.","family":"Nicol","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology College of Pharmacy University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelyn A.","family":"Pastick","sequence":"additional","affiliation":[{"name":"Department of Medicine Medical School University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jone\u00e9","family":"Taylor","sequence":"additional","affiliation":[{"name":"New York City Office of the Chief Medical Examiner and New York University New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivie C.","family":"Namuju","sequence":"additional","affiliation":[{"name":"Infectious Disease Institute of Makerere University Kampala Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Rhein","sequence":"additional","affiliation":[{"name":"Department of Medicine Medical School University of Minnesota Minneapolis Minnesota USA"},{"name":"Infectious Disease Institute of Makerere University Kampala Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darlisha A.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Medicine Medical School University of Minnesota Minneapolis Minnesota USA"},{"name":"Infectious Disease Institute of Makerere University Kampala Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Meya","sequence":"additional","affiliation":[{"name":"Department of Medicine Medical School University of Minnesota Minneapolis Minnesota USA"},{"name":"Infectious Disease Institute of Makerere University Kampala Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Boulware","sequence":"additional","affiliation":[{"name":"Department of Medicine Medical School University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Lukande","sequence":"additional","affiliation":[{"name":"Department of Pathology Makerere University Kampala Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,10]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/44755"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2011.02457.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2007.31"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-013-9306-4"},{"key":"e_1_2_10_5_1","first-page":"2587094","article-title":"Pharmacokinetic, pharmacogenetic, and other factors influencing CNS penetration of antiretrovirals","volume":"2016","author":"Nwogu J.N.","year":"2016","journal-title":"AIDS Res. 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