{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:42:09Z","timestamp":1775151729797,"version":"3.50.1"},"reference-count":27,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Raltegravir is an antiretroviral with potential value for preexposure prophylaxis (PrEP) against HIV, but the intracellular pharmacokinetics in genital tissue have not been described. In this study, healthy, HIV-uninfected nonpregnant women took 400 mg of raltegravir twice daily for 22 days. On day 8, 15, and 22, blood was collected 0, 4, 6, 8, and 12 h and cervical biopsy specimens taken 0, 6, and 12 h after raltegravir dosing. Plasma and intracellular raltegravir concentrations in peripheral blood mononuclear cells (PBMC) and cervical tissue were measured by tandem mass spectrometry. Linear mixed effects models evaluated correlations between different sample types, as well as differences in concentration between phases of the menstrual cycle. Ten women were enrolled: 9 completed all three visits and 1 completed two visits. The age (mean \u00b1 standard deviation) of participants was 30 \u00b1 8 years. Trough plasma concentrations of raltegravir 12 h after a directly observed dose were above the HIV 95% inhibitory concentration (IC\n            <jats:sub>95<\/jats:sub>\n            ) of 33 nM (14.6 ng\/ml) in 96% of measurements, compared to 67% of PBMC and 89% of cervical tissue trough values. Across all measurements, only 2% (3\/135) of plasma values fell below the IC\n            <jats:sub>95<\/jats:sub>\n            , compared to 10% (13\/135) for PBMC and 6% (5\/81) for cervical tissue. There was no impact of menstrual phase on raltegravir concentrations. In conclusion, cervical tissue raltegravir concentrations were no greater than plasma concentrations, and \u223c10% of all cervical tissue trough values were below the IC\n            <jats:sub>95<\/jats:sub>\n            , making the current twice-daily formulation of raltegravir impractical for PrEP.\n          <\/jats:p>","DOI":"10.1128\/aac.02757-13","type":"journal-article","created":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T04:54:28Z","timestamp":1396328068000},"page":"3360-3365","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Correlation between Plasma, Intracellular, and Cervical Tissue Levels of Raltegravir at Steady-State Dosing in Healthy Women"],"prefix":"10.1128","volume":"58","author":[{"given":"Caroline","family":"Mitchell","sequence":"first","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Roemer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evangelyn","family":"Nkwopara","sequence":"additional","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Robbins","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theodore","family":"Cory","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tessa","family":"Rue","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Washington, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Courtney V.","family":"Fletcher","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Frenkel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Washington, Seattle, Washington, USA"},{"name":"Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA"},{"name":"Seattle Children's Research Institute, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199411033311801"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)80008-7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1011205"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1108524"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e3182986f69"},{"key":"e_1_3_2_7_2","volume-title":"Consolidated guidelines on the use of antiretrovirals for the treatment and prevention of HIV infection","author":"WHO","year":"2013","unstructured":"WHO. 2013. 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