{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T15:30:15Z","timestamp":1767972615287,"version":"3.49.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"2","funder":[{"DOI":"10.13039\/100000030","name":"United States Centers for Disease Control and Prevention","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Event-driven HIV prevention strategies are a priority for users who do not require daily pre-exposure prophylaxis (PrEP). Regimens containing integrase strand transfer inhibitors (INSTIs) are under evaluation as alternatives to daily PrEP. To better understand INSTI distribution and inform dosing selection we compared the pharmacology of two-dose boosted elvitegravir and unboosted bictegravir regimens in MSM.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and methods<\/jats:title>\n                  <jats:p>Blood, rectal and penile secretions and rectal biopsies were collected from 63 HIV-negative MSM aged 18\u201349 years. Specimens were collected up to 96 h after two oral doses of tenofovir alafenamide and emtricitabine with elvitegravir boosted by cobicistat or unboosted bictegravir given 24 h apart. Antiretroviral drugs were measured by LC-MS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Mean bictegravir plasma concentrations remained above the 95% protein-adjusted effective concentration 96 h after dosing [273 (95% CI: 164\u2013456) ng\/mL] whereas elvitegravir plasma concentrations became undetectable 48 h after the second dose. Bictegravir and elvitegravir reached rectal tissues within 2 h after the first dose, and elvitegravir tissue concentrations [1.07 (0.38\u201313.51) ng\/mg] were greater than bictegravir concentrations [0.27 (0.15\u20130.70) ng\/mg]. Both INSTIs became undetectable in tissues within 96 h. Elvitegravir and bictegravir were not consistently detected in penile secretions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Whereas bictegravir plasma concentrations persist at least 4 days after a two-oral-dose HIV prophylaxis regimen, elvitegravir accumulates in mucosal tissues. Differing elvitegravir and bictegravir distribution may result in variable mucosal and systemic antiviral activity and can inform dosing strategies for event-driven HIV prevention.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac419","type":"journal-article","created":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T18:27:41Z","timestamp":1670956061000},"page":"497-503","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacology of boosted and unboosted integrase strand transfer inhibitors for two-dose event-driven HIV prevention regimens among men"],"prefix":"10.1093","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8165-3879","authenticated-orcid":false,"given":"Richard E","family":"Haaland","sequence":"first","affiliation":[{"name":"Division of HIV\/AIDS Prevention, Centers for Disease Control and Prevention , 1600 Clifton Road NE, M\/S H17-3, Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Fountain","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS Prevention, Centers for Disease Control and Prevention , 1600 Clifton Road NE, M\/S H17-3, Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Martin","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS Prevention, Centers for Disease Control and Prevention , 1600 Clifton Road NE, M\/S H17-3, Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuong","family":"Dinh","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS Prevention, Centers for Disease Control and Prevention , 1600 Clifton Road NE, M\/S H17-3, Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Holder","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS Prevention, Centers for Disease Control and Prevention , 1600 Clifton Road NE, M\/S H17-3, Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiancheng E","family":"Edwards","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS Prevention, Centers for Disease Control and Prevention , 1600 Clifton Road NE, M\/S H17-3, Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L Davis","family":"Lupo","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS Prevention, Centers for Disease Control and Prevention , 1600 Clifton Road NE, M\/S H17-3, Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LaShonda","family":"Hall","sequence":"additional","affiliation":[{"name":"The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine , Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Conway-Washington","sequence":"additional","affiliation":[{"name":"The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine , Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"Massud","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS Prevention, Centers for Disease Control and Prevention , 1600 Clifton Road NE, M\/S H17-3, Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J Gerardo","family":"Garc\u00eda-Lerma","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS Prevention, Centers for Disease Control and Prevention , 1600 Clifton Road NE, M\/S H17-3, Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5611-0119","authenticated-orcid":false,"given":"Colleen F","family":"Kelley","sequence":"additional","affiliation":[{"name":"The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine , Atlanta, GA , USA"},{"name":"Department of Epidemiology, Rollins School of Public Health, Emory University , Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walid M","family":"Heneine","sequence":"additional","affiliation":[{"name":"Division of HIV\/AIDS Prevention, Centers for Disease Control and Prevention , 1600 Clifton Road NE, M\/S H17-3, Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"2023020108205953700_dkac419-B1","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1056\/NEJMoa1108524","article-title":"Antiretroviral prophylaxis for HIV prevention in heterosexual men and women","volume":"367","author":"Baeten","year":"2012","journal-title":"N Engl J Med"},{"key":"2023020108205953700_dkac419-B2","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1056\/NEJMoa1011205","article-title":"Preexposure chemoprophylaxis for HIV prevention in men who have sex with men","volume":"363","author":"Grant","year":"2010","journal-title":"N Engl J Med"},{"key":"2023020108205953700_dkac419-B3","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1016\/S0140-6736(13)61127-7","article-title":"Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial","volume":"381","author":"Choopanya","year":"2013","journal-title":"Lancet"},{"key":"2023020108205953700_dkac419-B4","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0140-6736(20)31065-5","article-title":"Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial","volume":"396","author":"Mayer","year":"2020","journal-title":"Lancet"},{"key":"2023020108205953700_dkac419-B5","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1056\/NEJMoa2101016","article-title":"Cabotegravir for HIV prevention in cisgender men and transgender women","volume":"385","author":"Landovitz","year":"2021","journal-title":"N Engl J 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elvitegravir and dolutegravir in plasma and mucosal secretions in rhesus macaques","volume":"70","author":"Massud","year":"2015","journal-title":"J Antimicrob Chemother"},{"key":"2023020108205953700_dkac419-B21","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1097\/QAI.0b013e3181eb376b","article-title":"Pharmacokinetics and bioavailability of an integrase and novel pharmacoenhancer-containing single-tablet fixed-dose combination regimen for the treatment of HIV","volume":"55","author":"German","year":"2010","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2023020108205953700_dkac419-B22","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1080\/17425255.2019.1604685","article-title":"Pharmacokinetics and pharmacodynamics of cytochrome P450 inhibitors for HIV treatment","volume":"15","author":"Gong","year":"2019","journal-title":"Expert Opin Drug Metab 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