{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:31:30Z","timestamp":1791685890337,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T00:00:00Z","timestamp":1591833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R01 AI\u2010124965"],"award-info":[{"award-number":["1R01 AI\u2010124965"]}],"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":["U01 AI\u2010105872"],"award-info":[{"award-number":["U01 AI\u2010105872"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:p>The secondary lymphoid tissues (LT), lymph nodes (LN) and gut\u2010associated lymphoid tissue are the primary sites of HIV replication and where the latent pool of virus is maintained. We compared the pharmacokinetics of tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in LT of 13 HIV\u2010infected persons receiving a TDF\u2010containing antiretroviral regimen who subsequently switched to a TAF\u2010containing regimen. Study participants were on stable antiretroviral therapy for \u226512\u00a0months with plasma HIV\u2010RNA\u00a0&lt;\u00a048 copies\/mL for 6\u00a0months before enrollment and entry CD4 cell counts\u00a0&gt;\u00a0300\u00a0cells\/\u00b5L. Intracellular concentrations of tenofovir\u2010diphosphate (TFV\u2010DP) and emtricitabine\u2010triphosphate (FTC\u2010TP) were quantified in PBMCs and in mononuclear cells obtained from LN, ileum and rectal tissues. With TAF, the TFV\u2010DP concentrations in PBMCs and LN were 7.3\u2010fold and 6.4\u2010fold higher (ratios of geometric means of TAF to TDF), respectively, compared with TDF; ileal and rectal concentrations, however, were lower with geometric mean ratios of 0.14 and 0.18, respectively. A statistically significant relationship was observed between PBMC and LN concentrations of TFV\u2010DP. During TDF\u2010containing therapy, the expected effect of cobicistat to increase TFV plasma concentrations was observed, as were higher TFV\u2010DP concentrations in PBMCs and mononuclear cells from LN, ileum and rectal tissues. The higher TFV\u2010DP concentrations achieved with TAF in the LN provides the first human correlate of the observation in animals that TAF produced higher tenofovir LN concentrations. The ability to increase LN concentrations allows investigations of whether antiretroviral regimens with improved LN pharmacokinetics elicit a more complete virologic response in that compartment.<\/jats:p>","DOI":"10.1002\/cpt.1883","type":"journal-article","created":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T06:14:05Z","timestamp":1589004845000},"page":"971-975","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["The Lymphoid Tissue Pharmacokinetics of Tenofovir Disoproxil Fumarate and Tenofovir Alafenamide in HIV\u2010Infected Persons"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3703-7849","authenticated-orcid":false,"given":"Courtney V.","family":"Fletcher","sequence":"first","affiliation":[{"name":"Antiviral Pharmacology Laboratory University of Nebraska Medical Center Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony T.","family":"Podany","sequence":"additional","affiliation":[{"name":"Antiviral Pharmacology Laboratory University of Nebraska Medical Center Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Thorkelson","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Department of Medicine University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee C.","family":"Winchester","sequence":"additional","affiliation":[{"name":"Antiviral Pharmacology Laboratory University of Nebraska Medical Center Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Mykris","sequence":"additional","affiliation":[{"name":"Antiviral Pharmacology Laboratory University of Nebraska Medical Center Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodi","family":"Anderson","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Department of Medicine University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siri","family":"Jorstad","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Department of Medicine University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason V.","family":"Baker","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Department of Medicine University of Minnesota Minneapolis Minnesota USA"},{"name":"Infectious Diseases Hennepin Healthcare Research Institute (HHRI) Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy W.","family":"Schacker","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Department of Medicine University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,11]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0155100"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4411"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1318249111"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000002026"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16933"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2018.04.002"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2017.0072"},{"key":"e_1_2_10_8_1","unstructured":"Panel on Antiretroviral Guidelines for Adults and Adolescents.Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. 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In Conference on Retroviruses and Opportunistic Infections (CROI)."},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01064-08"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01089-12"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00733-08"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01013-06"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2018.07.032"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpt.1883","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1883","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.1883","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1883","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T13:29:02Z","timestamp":1699363742000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.1883"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,11]]},"references-count":25,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1002\/cpt.1883"],"URL":"https:\/\/doi.org\/10.1002\/cpt.1883","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,11]]},"assertion":[{"value":"2020-01-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}