{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T16:57:07Z","timestamp":1774371427672,"version":"3.50.1"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"National Institute of Neurologic Diseases and Stroke","award":["R21NS108344"],"award-info":[{"award-number":["R21NS108344"]}]},{"name":"National Institute of Neurologic Diseases and Stroke","award":["R01NS086312"],"award-info":[{"award-number":["R01NS086312"]}]},{"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\/100007249","name":"University of Minnesota","doi-asserted-by":"publisher","award":["UL1TR002494"],"award-info":[{"award-number":["UL1TR002494"]}],"id":[{"id":"10.13039\/100007249","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinical and Translational Science Award","award":["UL1TR002494"],"award-info":[{"award-number":["UL1TR002494"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Optimal penetration of anti-infectives in the female genital tract (FGT) is paramount in the treatment and prevention of infectious diseases. While exposure of anti-infectives in lower FGT tissues (e.g. cervix, vagina) has been described, little data exist on upper genital tissues (e.g. ovary, uterus).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Autopsies were performed and post-mortem tissues were collected within 24\u2005h of death for female participants with advanced HIV in Uganda (n\u200a=\u200a27). Tenofovir, lamivudine, efavirenz and fluconazole concentrations were measured using LC-MS\/MS in plasma, ovarian, uterine, cervical and vaginal tissues. Tissue penetration was calculated as tissue-to-plasma concentration ratios (TPRs).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>TPRs of tenofovir, lamivudine and fluconazole were highest in vaginal tissue (medians 1.86, 1.83 and 0.94, respectively), while the TPR of efavirenz was highest in ovarian tissue (median 0.65). With cervix as a reference compartment, vaginal TPRs were significantly higher than cervical for all four drugs; TPRs of efavirenz in uterine and ovarian compartments were also significantly higher than cervical. Most of the post-mortem FGT samples had a TPR of greater than 1 for tenofovir and lamivudine, while less than 50% had a TPR of greater than 1 for both efavirenz and fluconazole.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Penetration of anti-infectives was not homogeneous among the FGT compartments. Approximately 70% of FGT tissues had a TPR of greater than 1 for tenofovir and lamivudine, favouring the prevention of local HIV replication and transmission in the FGT.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac300","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T05:13:56Z","timestamp":1663132436000},"page":"3180-3186","source":"Crossref","is-referenced-by-count":3,"title":["A post-mortem analysis of tenofovir, lamivudine, efavirenz and fluconazole penetration in female genital tissues"],"prefix":"10.1093","volume":"77","author":[{"given":"Fan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, University of Minnesota , Minneapolis, MN , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivie C","family":"Namuju","sequence":"additional","affiliation":[{"name":"Infectious Disease Institute , Kampala , Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1306-1713","authenticated-orcid":false,"given":"Katelyn A","family":"Pastick","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota , Minneapolis, MN , USA"},{"name":"Massachusetts General Hospital , Boston, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kizito","family":"Abdusalaamu","sequence":"additional","affiliation":[{"name":"Infectious Disease Institute , Kampala , Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Usha","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, University of Minnesota , Minneapolis, MN , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsey","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, University of Minnesota , Minneapolis, MN , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4715-0060","authenticated-orcid":false,"given":"David R","family":"Boulware","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota , Minneapolis, MN , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Lukande","sequence":"additional","affiliation":[{"name":"Makerere University , Kampala , Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David B","family":"Meya","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota , Minneapolis, MN , USA"},{"name":"Makerere University , Kampala , Uganda"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5513-5509","authenticated-orcid":false,"given":"Melanie R","family":"Nicol","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, University of Minnesota , Minneapolis, MN , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"2023062919535575600_dkac300-B1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1004440","article-title":"Vaginal challenge with an SIV-based dual reporter system reveals that infection can occur throughout the upper and lower female reproductive tract","volume":"10","author":"Stieh","year":"2014","journal-title":"PLoS Pathog"},{"key":"2023062919535575600_dkac300-B2","first-page":"223","article-title":"Tuboovarian abscess associated with Candida glabrata in a woman with an intrauterine device. 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