{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:59:58Z","timestamp":1785373198820,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P30AI050410"],"award-info":[{"award-number":["P30AI050410"]}],"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":["R21AI145646"],"award-info":[{"award-number":["R21AI145646"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Female sex hormones used in feminizing hormone therapy (FHT) may influence activation and persistence of HIV pre\u2010exposure prophylaxis (PrEP) medications. The clinical relevance of this interaction remains unclear, particularly for transgender and cisgender women (TGW and CGW). To address this gap, we examined drug metabolites in HIV susceptible cells isolated from blood and rectal tissues of TGW and CGW.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      We enrolled 23 TGW, 13 on FHT and 10 CGW. Participants received five directly observed daily PrEP doses: emtricitabine 200\u2009mg with either tenofovir disoproxil fumarate 300\u2009mg (FTC\/TDF) or tenofovir alafenamide 25\u2009mg (FTC\/TAF). Blood and rectal tissue samples were obtained. Mononuclear and CD4\n                      <jats:sup>+<\/jats:sup>\n                      cells were isolated and analysed for intracellular triphosphorylated nucleotides (TFVdp and FTCtp) and total nucleotide pools (pTFV and pFTC) using HPLC\u2010MS\/MS. Serum hormone concentrations were quantified via enzyme immunoassay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Conclusion<\/jats:title>\n                    <jats:p>\n                      Total nucleotide pools (pTFV and pFTC) correlated with active metabolites (TFVdp and FTCtp) in blood and rectal CD4\n                      <jats:sup>+<\/jats:sup>\n                      cells (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009&gt;\u20090.75,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.001). No significant differences in pTFV or pFTC concentrations were observed between high and low oestradiol groups in either CGW or TGW (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u2009.1). No correlation was observed between serum oestradiol concentrations and nucleotide concentrations. TAF resulted in 6.8\u2010fold higher median pTFV concentrations in blood CD4\n                      <jats:sup>+<\/jats:sup>\n                      cells (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.001) but eightfold lower median pTFV concentrations in rectal CD4\n                      <jats:sup>+<\/jats:sup>\n                      cells compared to TDF (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.008). These findings suggest that neither endogenous hormonal fluctuations in CGW nor exogenous FHT in TGW adversely impact intracellular PrEP pharmacology in key HIV target cells.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70586","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T12:02:39Z","timestamp":1778155359000},"page":"2949-2959","source":"Crossref","is-referenced-by-count":0,"title":["PrEP at the site of action in cisgender and transgender women: A pharmacology study of blood and rectal CD4\n                    <sup>+<\/sup>\n                    lymphocytes"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6587-6968","authenticated-orcid":false,"given":"Elizabeth","family":"Hastie","sequence":"first","affiliation":[{"name":"University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megha","family":"Srivasta","sequence":"additional","affiliation":[{"name":"University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward R.","family":"Cachay","sequence":"additional","affiliation":[{"name":"Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Burke","sequence":"additional","affiliation":[{"name":"University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gianella","sequence":"additional","affiliation":[{"name":"University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Rawlings","sequence":"additional","affiliation":[{"name":"Maine Medical Center  Portland Maine USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank Z.","family":"Stanczyk","sequence":"additional","affiliation":[{"name":"University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Sykes","sequence":"additional","affiliation":[{"name":"University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela D. M.","family":"Kashuba","sequence":"additional","affiliation":[{"name":"University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Blumenthal","sequence":"additional","affiliation":[{"name":"University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie L.","family":"Cottrell","sequence":"additional","affiliation":[{"name":"University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1011205"},{"key":"e_1_2_11_3_1","unstructured":"Preexposure prophylaxis for the prevention of HIV infection in the United States\u20142021 update: a clinical practice guideline. 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