{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T01:42:55Z","timestamp":1774316575411,"version":"3.50.1"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2018,12,18]],"date-time":"2018-12-18T00:00:00Z","timestamp":1545091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","award":["RD16\/0025\/0003"],"award-info":[{"award-number":["RD16\/0025\/0003"]}],"id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 AI50410"],"award-info":[{"award-number":["P30 AI50410"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>This study assessed the penetration and efficacy of tenofovir alafenamide (TAF) in the male genital tract (MGT) and the semen quality of individuals infected with human immunodeficiency virus (HIV)-1 who were treated with a TAF-containing regimen.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This was a prospective, open-label, single-arm study of 14 virologically-suppressed, HIV-1\u2013infected men on stable antiretroviral therapy with elvitegravir, cobicistat, emtricitabine (E\/C\/F) and tenofovir disoproxil fumarate (TDF) who switched to E\/C\/F and TAF. At baseline (pre-switch) and at 12 weeks post-switch, we measured HIV-1 RNA in seminal plasma (SP) and blood plasma (BP), tenofovir (TFV) in SP and BP, and TFV-diphosphate (dp) in peripheral blood mononuclear cells (PBMCs) and seminal mononuclear cells (SMCs) at the end of the dosing interval (C24h). Semen quality was assessed before switching and after 12 weeks on TAF.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>With TAF, TFV C24 was 11.9-fold higher in SP than in BP. This concentration was significantly lower than TFV C24 in SP with TDF, but 9.6-fold higher than the 50% inhibitory concentration (IC50) (11.5 ng\/mL). By contrast, the median TFV-dp concentration achieved with TAF in SMCs was 6% that of TFV-dp in PBMCs. The TFV-dp SMC:PBMC ratio was also significantly lower with TAF. Nonetheless, TFV-dp C24 in SMC was comparable with TAF and TDF. All the patients had HIV-1 RNA &lt;40 copies\/mL in BP and SP at baseline and at 12 weeks post-switch. No significant differences were observed in semen quality between TAF and TDF.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Extracellular and intracellular seminal TFV distribution differs between TAF and TDF. Nevertheless, both formulations, combined with elvitegravir\/cobicistat\/emtricitabine, maintained HIV-1 RNA suppression in semen. Differences in MGT distribution were not associated with differences in semen quality.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>EudraCT: 2016-001371-69<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciy1074","type":"journal-article","created":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T15:11:47Z","timestamp":1544627507000},"page":"1403-1409","source":"Crossref","is-referenced-by-count":10,"title":["Seminal Tenofovir Concentrations, Viral Suppression, and Semen Quality With Tenofovir Alafenamide, Compared With Tenofovir Disoproxil Fumarate (Spanish HIV\/AIDS Research Network, PreEC\/RIS 40)"],"prefix":"10.1093","volume":"69","author":[{"given":"Arkaitz","family":"Imaz","sequence":"first","affiliation":[{"name":"Human Immunodeficiency Virus and Sexually Transmitted Infections Unit, Department of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordi","family":"Niub\u00f3","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Hospital Universitari de Bellvitge-Bellvitge Biomedical Research Institute, L\u2019Hospitalet de Llobregat, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mackenzie L","family":"Cottrell","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilia","family":"Perez","sequence":"additional","affiliation":[{"name":"Laboratori Cl\u00ednic L\u2019Hospitalet, L\u2019Hospitalet de Llobregat, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela D M","family":"Kashuba","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan M","family":"Tiraboschi","sequence":"additional","affiliation":[{"name":"Human Immunodeficiency Virus and Sexually Transmitted Infections Unit, Department of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Morenilla","sequence":"additional","affiliation":[{"name":"Human Immunodeficiency Virus and Sexually Transmitted Infections Unit, Department of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benito","family":"Garcia","sequence":"additional","affiliation":[{"name":"Human Immunodeficiency Virus and Sexually Transmitted Infections Unit, Department of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Podzamczer","sequence":"additional","affiliation":[{"name":"Human Immunodeficiency Virus and Sexually Transmitted Infections Unit, Department of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,12,18]]},"reference":[{"key":"2019092701015367000_CIT0001","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1097\/COH.0000000000000287","article-title":"Persistent HIV-1 replication during antiretroviral therapy","volume":"11","author":"Martinez-Picado","year":"2016","journal-title":"Curr Opin HIV AIDS"},{"key":"2019092701015367000_CIT0002","first-page":"162","article-title":"Genital tract reservoirs","volume":"1","author":"Galvin","year":"2006","journal-title":"Curr Opin HIV AIDS"},{"key":"2019092701015367000_CIT0003","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1097\/COH.0b013e32833a0b69","article-title":"Antiretroviral drug concentrations in the male and female genital tract: implications for the sexual transmission of HIV","volume":"5","author":"Taylor","year":"2010","journal-title":"Curr Opin HIV AIDS"},{"key":"2019092701015367000_CIT0004","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1056\/NEJMoa1600693","article-title":"Antiretroviral therapy for the prevention of HIV-1 transmission","volume":"375","author":"Cohen","year":"2016","journal-title":"N Engl J Med"},{"key":"2019092701015367000_CIT0005","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1016\/S0140-6736(15)60616-X","article-title":"Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials","volume":"385","author":"Sax","year":"2015","journal-title":"Lancet"},{"key":"2019092701015367000_CIT0006","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1097\/QAD.0000000000001817","article-title":"A week-48 randomized phase-3 trial of darunavir\/cobicistat\/emtricitabine\/tenofovir alafenamide in treatment-naive HIV-1 patients","volume":"32","author":"Eron","year":"2018","journal-title":"AIDS"},{"key":"2019092701015367000_CIT0007","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.1016\/S2352-3018(17)30179-0","article-title":"Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial","volume":"5","author":"Orkin","year":"2018","journal-title":"Lancet HIV"},{"key":"2019092701015367000_CIT0008","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1080\/14787210.2017.1286736","article-title":"Tenofovir alafenamide, emtricitabine, elvitegravir, and cobicistat combination therapy for the treatment of HIV","volume":"15","author":"Imaz","year":"2017","journal-title":"Expert Rev Anti Infect Ther"},{"key":"2019092701015367000_CIT0009","volume-title":"Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents","author":"Panel on Antiretroviral Guidelines for Adults and Adolescents"},{"key":"2019092701015367000_CIT0010","unstructured":"European AIDS Clinical Society (EACS) Guidelines. Clinical management and treatment of HIV infected adults in Europe. Version 9.1. Available at: http:\/\/www.europeanaidsclinicalsociety.org. Accessed 19 November 2018."},{"key":"2019092701015367000_CIT0011","unstructured":"AIDS Study Group (GESIDA) of the Spanish Society of Infectious Diseases, Clinical Microbiology, the National AIDS Plan. GESIDA\/National AIDS plan consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus. Available at: http:\/\/gesida-seimc.org\/wp-content\/uploads\/2017\/02\/gesida-guiasclinicas-2016-tar.pdf. Accessed 1 June 2018."},{"key":"2019092701015367000_CIT0012","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S1473-3099(15)00348-5","article-title":"Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study","volume":"16","author":"Mills","year":"2016","journal-title":"Lancet Infect Dis"},{"key":"2019092701015367000_CIT0013","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1097\/QAI.0000000000001186","article-title":"Brief report: switching to tenofovir alafenamide, coformulated with elvitegravir, cobicistat, and emtricitabine, in HIV-infected adults with renal impairment: 96-week results from a single-arm, multicenter, open-label phase 3 study","volume":"74","author":"Post","year":"2017","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2019092701015367000_CIT0014","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1097\/QAI.0000000000001193","article-title":"A randomized, open-label trial to evaluate switching to elvitegravir\/cobicistat\/emtricitabine\/tenofovir alafenamide plus darunavir in treatment-experienced HIV-1-infected adults","volume":"74","author":"Huhn","year":"2017","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2019092701015367000_CIT0015","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1097\/QAI.0b013e3181632cc3","article-title":"The pharmacokinetics and viral activity of tenofovir in the male genital tract","volume":"47","author":"Vourvahis","year":"2008","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2019092701015367000_CIT0016","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1097\/QAI.0b013e3182965d45","article-title":"Antiviral activity, safety, and pharmacokinetics\/pharmacodynamics of tenofovir alafenamide as 10-day monotherapy in HIV-1-positive adults","volume":"63","author":"Ruane","year":"2013","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2019092701015367000_CIT0017","doi-asserted-by":"publisher","DOI":"10.3851\/IMP3277","article-title":"Differential extracellular, but similar intracellular, disposition of two tenofovir formulations in the male genital tract","author":"Dumond","year":"2018","journal-title":"Antivir Ther"},{"key":"2019092701015367000_CIT0018","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1097\/QAD.0b013e3282f4de10","article-title":"Effects of antiretroviral therapy on semen quality","volume":"22","author":"van Leeuwen","year":"2008","journal-title":"AIDS"},{"key":"2019092701015367000_CIT0019","volume-title":"WHO laboratory manual for the examination and processing of human semen","author":"World Health Organization","year":"2010","edition":"5th ed"},{"key":"2019092701015367000_CIT0020","volume-title":"Gilead Sciences. Viread [Package Insert]","year":"2010"},{"key":"2019092701015367000_CIT0021","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1093\/infdis\/jiw077","article-title":"A translational pharmacology approach to predicting outcomes of preexposure prophylaxis against HIV in Men and women using tenofovir disoproxil fumarate with or without emtricitabine","volume":"214","author":"Cottrell","year":"2016","journal-title":"J Infect Dis"},{"key":"2019092701015367000_CIT0022","doi-asserted-by":"crossref","first-page":"625983","DOI":"10.1155\/2012\/625983","article-title":"The impact of macrophage nucleotide pools on HIV-1 reverse transcription, viral replication, and the development of novel antiviral agents","volume":"2012","author":"Gavegnano","year":"2012","journal-title":"Mol Biol Int"},{"key":"2019092701015367000_CIT0023","doi-asserted-by":"crossref","first-page":"6145","DOI":"10.1128\/AAC.03591-14","article-title":"The combined anti-HIV-1 activities of emtricitabine and tenofovir plus the integrase inhibitor elvitegravir or raltegravir show high levels of synergy in vitro","volume":"58","author":"Kulkarni","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"2019092701015367000_CIT0024","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1097\/FTD.0b013e31811fef29","article-title":"Semen quality and drug concentrations in seminal plasma of patients using a didanosine or didanosine plus tenofovir containing antiretroviral regimen","volume":"29","author":"Lowe","year":"2007","journal-title":"Ther Drug Monit"},{"key":"2019092701015367000_CIT0025","doi-asserted-by":"crossref","first-page":"77ra29","DOI":"10.1126\/scitranslmed.3001888","article-title":"Genital HIV-1 RNA predicts risk of heterosexual HIV-1 transmission","volume":"3","author":"Baeten","year":"2011","journal-title":"Sci Transl Med"},{"key":"2019092701015367000_CIT0026","doi-asserted-by":"crossref","first-page":"e1001053","DOI":"10.1371\/journal.ppat.1001053","article-title":"HIV-1 populations in semen arise through multiple mechanisms","volume":"6","author":"Anderson","year":"2010","journal-title":"PLOS Pathog"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/cid\/article-pdf\/69\/8\/1403\/30063317\/ciy1074.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T01:02:24Z","timestamp":1569546144000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/69\/8\/1403\/5251937"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,18]]},"references-count":26,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2018,12,18]]},"published-print":{"date-parts":[[2019,9,27]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciy1074","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,10,15]]},"published":{"date-parts":[[2018,12,18]]}}}