{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T19:27:28Z","timestamp":1775762848990,"version":"3.50.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T00:00:00Z","timestamp":1718841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurologic Disorders and Stroke","doi-asserted-by":"publisher","award":["R21NS108344"],"award-info":[{"award-number":["R21NS108344"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurologic Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS086312"],"award-info":[{"award-number":["R01NS086312"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K08AI134262"],"award-info":[{"award-number":["K08AI134262"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U01AI125003-04S1"],"award-info":[{"award-number":["U01AI125003-04S1"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01DA05315"],"award-info":[{"award-number":["R01DA05315"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University"},{"name":"of Minnesota"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1UM1TR004405-01A1"],"award-info":[{"award-number":["1UM1TR004405-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Central nervous system (CNS) compartmentalization provides opportunity for human immunodeficiency virus (HIV) persistence and resistance development. Differences between cerebrospinal fluid (CSF) and cerebral matter regarding HIV persistence are well described. However, CSF is often used as surrogate for CNS drug exposure, and knowledge from solid brain tissue is rare.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Dolutegravir, tenofovir, lamivudine, and efavirenz concentrations were measured across 13 CNS regions plus plasma in samples collected during autopsy in 49 Ugandan decedents. Median time from death to autopsy was 8 hours (interquartile range, 5\u201315 hours). To evaluate postmortem redistribution, a time course study was performed in a mouse model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Regions with the highest penetration ratios were choroid plexus\/arachnoid (dolutegravir and tenofovir), CSF (lamivudine), and cervical spinal cord\/meninges (efavirenz); the lowest were corpus callosum (dolutegravir and tenofovir), frontal lobe (lamivudine), and parietal lobe (efavirenz). On average, brain concentrations were 84%, 87%, and 76% of CSF for dolutegravir, tenofovir, and lamivudine, respectively. Postmortem redistribution was observed in the mouse model, with tenofovir and lamivudine concentration increased by 350% and efavirenz concentration decreased by 24% at 24 hours postmortem.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Analysis of postmortem tissue provides a unique opportunity to investigate CNS antiretroviral penetration. Regional differences were observed paving the way to identify mechanisms of viral compartmentalization and\/or neurotoxicity.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiae325","type":"journal-article","created":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T18:05:16Z","timestamp":1718906716000},"page":"1215-1223","source":"Crossref","is-referenced-by-count":5,"title":["Postmortem Analysis of Dolutegravir, Tenofovir, Lamivudine, and Efavirenz Penetration in Multiple Central Nervous System Compartments"],"prefix":"10.1093","volume":"230","author":[{"given":"Fan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, University of Minnesota , Minneapolis, Minnesota ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kara","family":"Rademeyer","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Outcomes Sciences, Virginia Commonwealth University , Richmond, Virginia ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivie C","family":"Namuju","sequence":"additional","affiliation":[{"name":"Department of Research, Infectious Diseases Institute , Kampala ,","place":["Uganda"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kizito","family":"Abdusalaamu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Makerere University, Kampala ,","place":["Uganda"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Fisher","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Analytical Services, University of Minnesota , Minneapolis, Minnesota ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8854-0321","authenticated-orcid":false,"given":"David B","family":"Meya","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota , 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