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Transgender women (TGW) have increased HIV risk, but have been underrepresented in trials. For TGW on oestrogens for gender\u2010affirming hormone treatment (GAHT), TDF\/FTC\u2010oestrogen interactions may negatively affect HIV prevention or gender\u2010affirming goals. Our aim was to evaluate any pharmacokinetic drug\u2010drug interaction between GAHT and TDF\/FTC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a pharmacokinetic study, in an urban outpatient setting in 2016 to 2018, of the effects of GAHT on TFV, FTC and the active forms TFV diphosphate (TFV\u2010DP) and FTC triphosphate (FTC\u2010TP) in eight TGW and eight cisgender men (CGM). At screening, participants were HIV negative. TGW were to maintain their GAHT regimens and have plasma oestradiol concentrations &gt;100\u00a0pg\/mL. Under direct observation, participants took oral TDF\/FTC daily for seven days. At the last dose, blood was collected pre\u2010dose, one, two, four, six, eight and twenty\u2010four hours, and colon biopsies were collected at 24\u00a0hours to measure drug concentration. TGW versus CGM concentration comparisons used non\u2010parametric tests. Blood and colon tissue were also obtained to assess kinase expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Plasma TFV and FTC C<jats:sub>24<\/jats:sub> (trough) concentrations in TGW were lower by 32% (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.010) and 32% (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.038) respectively, when compared to CGM. Plasma TFV and FTC 24\u2010hr area under the concentration\u2010time curve in TGW trended toward and was significantly lower by 27% (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.065) and 24% (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.028) respectively. Peak plasma TFV and FTC concentrations, as well as all other pharmacokinetic measures, were not statistically significant when comparing TGW to CGM. Oestradiol concentrations were not different comparing before and after TDF\/FTC dosing. Plasma oestrogen concentration, renal function (estimated creatinine clearance and glomerular filtration rate), and TFV and FTC plasma concentrations (trough and area under the concentration\u2010time curve) were all correlated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>GAHT modestly reduces both TFV and FTC plasma concentrations. In TGW taking GAHT, it is unknown if this reduction will impact the HIV protective efficacy of a daily PrEP regimen. However, the combination of an on demand (2\u00a0+\u00a01\u00a0+\u00a01) PrEP regimen and GAHT may result in concentrations too low for reliable prevention of HIV infection.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25405","type":"journal-article","created":{"date-parts":[[2019,11,6]],"date-time":"2019-11-06T11:04:36Z","timestamp":1573038276000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Transgender women on oral HIV pre\u2010exposure prophylaxis have significantly lower tenofovir and emtricitabine concentrations when also taking oestrogen when compared to cisgender men"],"prefix":"10.1002","volume":"22","author":[{"given":"Eugenie","family":"Shieh","sequence":"first","affiliation":[{"name":"Department of Medicine (Clinical Pharmacology) Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A","family":"Marzinke","sequence":"additional","affiliation":[{"name":"Department of Medicine (Clinical Pharmacology) Johns Hopkins University School of Medicine Baltimore MD USA"},{"name":"Department of Pathology Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Department of Medicine (Clinical Pharmacology) Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allyson","family":"Hamlin","sequence":"additional","affiliation":[{"name":"Department of Medicine (Clinical Pharmacology) Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Bakshi","sequence":"additional","affiliation":[{"name":"Department of Medicine (Clinical Pharmacology) Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wutyi","family":"Aung","sequence":"additional","affiliation":[{"name":"Department of Medicine (Clinical Pharmacology) Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Breakey","sequence":"additional","affiliation":[{"name":"Department of Medicine (Clinical Pharmacology) Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonia","family":"Poteat","sequence":"additional","affiliation":[{"name":"Department of Social Medicine University of North Carolina Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Medicine (Endocrinology) Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namandj\u00e9 N","family":"Bumpus","sequence":"additional","affiliation":[{"name":"Department of Medicine (Clinical Pharmacology) Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5696-8665","authenticated-orcid":false,"given":"Craig W","family":"Hendrix","sequence":"additional","affiliation":[{"name":"Department of Medicine (Clinical Pharmacology) Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(12)70315-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10461-017-1869-4"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/trgh.2016.0033"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10461-016-1387-9"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1011205"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(15)00206-4"},{"key":"e_1_2_9_8_1","volume-title":"National Transgender Discrimination Survey Report on Health and Health Care","author":"Grant JM","year":"2010"},{"key":"e_1_2_9_9_1","unstructured":"PoteatT CooneyE MalikM YamanisT LujanM WirtzA.Predictors of Willingness to Take PrEP among Black and Latina Transgender Women. 25th Conference on Retroviruses and Opportunistic Infections. 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