{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:18:34Z","timestamp":1791512314341,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Int AIDS Soc."],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Hormonal contraceptives are among the most effective forms of reversible contraception, but many other compounds, including some antiretrovirals, have clinically meaningful drug\u2013drug interactions (DDIs) with hormonal contraceptives. Islatravir is a novel human immunodeficiency virus nucleoside reverse transcriptase translocation inhibitor currently in clinical development for treatment and prevention of HIV infection. A phase 1 clinical trial was conducted to evaluate the DDI of islatravir and the combination of oral contraceptive levonorgestrel (LNG)\/ethinyl estradiol (EE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was an open\u2010label, two\u2010period, fixed\u2010sequence, DDI clinical trial in healthy, postmenopausal or bilaterally oophorectomized females aged 18 through 65 years in the United States between October 2016 and January 2017. A single dose of LNG 0.15 mg\/EE 0.03 mg was given followed by a 7\u2010day washout. Islatravir, 20 mg, was then dosed once weekly for 3 weeks; a single dose of LNG 0.15 mg\/EE 0.03 mg was given concomitantly with the third dose of islatravir. Pharmacokinetic samples for plasma LNG and EE concentrations were collected pre\u2010dose and up to 120 hours post\u2010dose in each period. Safety and tolerability were assessed throughout the trial by clinical assessments, laboratory evaluations and examination of adverse events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and Discussion<\/jats:title><jats:p>Fourteen participants were enrolled. The pharmacokinetics of LNG and EE were not meaningfully altered by co\u2010administration with islatravir. For the comparison of (islatravir + LNG\/EE)\/(LNG\/EE alone), the geometric mean ratios (GMRs) (90% confidence intervals [CIs]) for LNG AUC<jats:sub>0\u2013inf<\/jats:sub> and <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> were 1.13 (1.06, 1.20) and 0.965 (0.881, 1.06), respectively. For EE, the GMRs (90% CI) for AUC<jats:sub>0\u2013inf<\/jats:sub> and <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> were 1.05 (0.981, 1.11) and 1.02 (0.971, 1.08), respectively. Co\u2010administration of all three drugs was generally well tolerated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results of this trial support the use of LNG\/EE contraceptives in combination with islatravir without dose adjustment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25858","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T08:39:07Z","timestamp":1640162347000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A phase 1, open\u2010label study to evaluate the drug interaction between islatravir (MK\u20108591) and the oral contraceptive levonorgestrel\/ethinyl estradiol in healthy adult females"],"prefix":"10.1002","volume":"24","author":[{"given":"Wendy","family":"Ankrom","sequence":"first","affiliation":[{"name":"Merck &amp; Co., Inc. Merck Research Labs  Kenilworth New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deanne","family":"Jackson Rudd","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc. Merck Research Labs  Kenilworth New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saijuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc. Merck Research Labs  Kenilworth New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry L.","family":"Fillgrove","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc. Merck Research Labs  Kenilworth New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kezia N.","family":"Gravesande","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc. 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