{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T02:22:21Z","timestamp":1649211741566},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,11,2]],"date-time":"2017-11-02T00:00:00Z","timestamp":1509580800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,11,2]],"date-time":"2017-11-02T00:00:00Z","timestamp":1509580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Gilead Sciences Canada Inc.","award":["IN-CA-236-1313"],"award-info":[{"award-number":["IN-CA-236-1313"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["AIDS Res Ther"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>As a simplification strategy for treatment-experienced HIV-infected patients who have achieved virologic suppression on a multi-drug, multi-class antiretroviral regimen, the aim of this study was to evaluate the safety, efficacy, and pharmacokinetics of once-daily elvitegravir\/cobicistat\/emtricitabine\/tenofovir disproxil fumarate (E\/C\/F\/TDF) with darunavir.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A single arm, open-label 48-week study was conducted of regimen simplification to E\/C\/F\/TDF plus darunavir 800\u00a0mg daily from stable therapy including two nucleoside\/nucleotide reverse transcriptase inhibitors, a ritonavir-boosted protease inhibitor, and an integrase inhibitor. Participants had plasma HIV viral load consistently &lt;\u00a0200 copies\/mL for \u2265\u00a06\u00a0months, estimated glomerular filtration rate (eGFR) \u2265\u00a060\u00a0mL\/min, and no genotypic resistance to major components of the study regimen. Plasma viral load was measured at weeks 2 and 4, then every 4\u00a0weeks throughout the study. Safety laboratory assessments were conducted at baseline and at weeks 12, 24, 36, and 48. Antiretroviral drug concentrations were measured at baseline and once \u2265\u00a02\u00a0weeks after the regimen change.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Ten HIV-infected adults (8 male and 2 female; median age 50.5\u00a0years) were enrolled. All maintained virologic suppression on the new regimen for 48\u00a0weeks. One subject experienced a decrease in eGFR from 62\u00a0mL\/min at baseline to 52\u00a0mL\/min at week 12; study medications were continued and his eGFR remained stable (50\u201359\u00a0mL\/min) thereafter. No subjects discontinued study medications for renal function changes or other adverse events. Darunavir trough concentration were lower on the new regimen than on darunavir\/ritonavir 800\/100\u00a0mg (n\u00a0=\u00a05; p\u00a0&lt;\u00a00.05).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Despite low darunavir trough concentrations, treatment simplification to a two-pill, once-daily regimen of E\/C\/F\/TDF plus darunavir was safe and effective for 48\u00a0weeks among 10 selected treatment-experienced HIV-infected patients.<\/jats:p>\n                <jats:p><jats:italic>Trial registration<\/jats:italic> The study protocol was registered with ClinicalTrials.gov (NCT02199613) on July 22, 2014<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12981-017-0185-4","type":"journal-article","created":{"date-parts":[[2017,11,2]],"date-time":"2017-11-02T15:52:52Z","timestamp":1509637972000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["HIV treatment simplification to elvitegravir\/cobicistat\/emtricitabine\/tenofovir disproxil fumarate (E\/C\/F\/TDF) plus darunavir: a pharmacokinetic study"],"prefix":"10.1186","volume":"14","author":[{"given":"Marianne","family":"Harris","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Ganase","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgit","family":"Watson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. Richard","family":"Harrigan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julio S. G.","family":"Montaner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark W.","family":"Hull","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,11,2]]},"reference":[{"key":"185_CR1","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/B978-1-4160-2882-6.50050-2","volume-title":"Global HIV\/AIDS medicine","author":"M Harris","year":"2008","unstructured":"Harris M, Harrigan PR, Montaner JSG. Chapter 46: Antiretroviral Therapy of Drug-resistant HIV. In: Volberding PA, Sande MA, Lange J, Greene WC, Gallant JE, editors. Global HIV\/AIDS medicine. Saunders: Elsevier; 2008. p. 537\u201345."},{"key":"185_CR2","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1056\/NEJMra1004180","volume":"365","author":"MA Wainberg","year":"2011","unstructured":"Wainberg MA, Zaharatos GJ, Brenner BG. Development of antiretroviral drug resistance. N Engl J Med. 2011;365:637\u201346.","journal-title":"N Engl J Med"},{"issue":"Suppl 2","key":"185_CR3","doi-asserted-by":"publisher","first-page":"S171","DOI":"10.1086\/313849","volume":"30","author":"MA Chesney","year":"2000","unstructured":"Chesney MA. Factors affecting adherence to antiretroviral therapy. Clin Infect Dis. 2000;30(Suppl 2):S171\u20136.","journal-title":"Clin Infect Dis"},{"key":"185_CR4","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1086\/630210","volume":"49","author":"Y Yazdanpanah","year":"2009","unstructured":"Yazdanpanah Y, Fagard C, Descamps D, et al. High rate of virologic suppression with raltegravir plus etravirine and darunavir\/ritonavir among treatment-experienced patients infected with multi-drug resistant HIV: results of the ANRS 139 TRIO trial. Clin Infect Dis. 2009;49:1441\u20139.","journal-title":"Clin Infect Dis"},{"key":"185_CR5","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1080\/13548506.2014.945601","volume":"20","author":"KR Claborn","year":"2015","unstructured":"Claborn KR, Meier E, Miller MB, Leffingwell TR. A systematic review of treatment fatigue among HIV-infected patients prescribed antiretroviral therapy. Psychol Health Med. 2015;20:255\u201365.","journal-title":"Psychol Health Med."},{"key":"185_CR6","unstructured":"Gilead Sciences Canada Inc. Stribild Product Monograph. Mississauga, Ontario, Canada; March 7, 2017."},{"key":"185_CR7","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1002\/phar.1237","volume":"33","author":"BM Shah","year":"2013","unstructured":"Shah BM, Schafer JJ, Priano J, Squires KE. Cobicistat: a new boost for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2013;33:1107\u201316.","journal-title":"Pharmacotherapy"},{"key":"185_CR8","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1097\/QAD.0b013e328345ee95","volume":"25","author":"P Cahn","year":"2011","unstructured":"Cahn P, Fourie J, Grinzstejn B, et al. Week 48 analysis of once-daily vs. twice-daily drunavir\/ritonavir in treatment-experienced HIV-1-infected patients. AIDS. 2011;25:929\u201339.","journal-title":"AIDS"},{"key":"185_CR9","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1310\/hct0906-418","volume":"9","author":"M Boffito","year":"2008","unstructured":"Boffito M, Miralles D, Hill A. Pharmacokinetics, efficacy, and safety of darunavir\/ritonavir 800\/100\u00a0mg once-daily in treatment-na\u00efve and -experienced patients. HIV Clin Trials. 2008;9:418\u201327.","journal-title":"HIV Clin Trials"},{"key":"185_CR10","unstructured":"Janssen Inc. Prezista Product monograph. Toronto, Ontario, Canada; April 7, 2017."},{"key":"185_CR11","unstructured":"Ramanathan S, Wang H, Szwarcberg J, Kearney BP. Safety\/tolerability, pharmacokinetics and boosting of twice-daily cobicistat administered alone or in combination with darunavir or tipranavir. In: 13th International Workshop on Clinical Pharmacology of HIV Therapy. Barcelona, Spain. April 16-18, 2012. (poster P08)."},{"key":"185_CR12","unstructured":"Ricard F, Wong A, Lebouche B, et al. Low darunavir concentrations in patients receiving Stribild (elvitegravir\/cobicistat\/emtricitabine\/tenofovir disproxil fumarate) and darunavir once daily. In: 16th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy. May 26\u201328, 2015. Washington, DC, USA. (poster 50)."},{"key":"185_CR13","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1093\/infdis\/jit043","volume":"207","author":"L Ryom","year":"2013","unstructured":"Ryom L, Mocroft A, Kirk O, et al. Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function: the D: a: D study. J Infect Dis. 2013;207:1359\u201369.","journal-title":"J Infect Dis"},{"key":"185_CR14","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1186\/1471-2458-12-234","volume":"12","author":"FM Islam","year":"2012","unstructured":"Islam FM, Wu J, Jansson J, Wilson DP. Relative risk of renal disease among people living with HIV: a systematic review and meta-analysis. BMC Public Health. 2012;12:234.","journal-title":"BMC Public Health"},{"key":"185_CR15","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1097\/QAD.0b013e328351f68f","volume":"26","author":"R Scherzer","year":"2012","unstructured":"Scherzer R, Estrella M, Li Y, Deeks SG, Grunfeld C, Shlipak MG. Association of tenofovir exposure with kidney disease risk in HIV infection. AIDS. 2012;26:867\u201375.","journal-title":"AIDS"},{"key":"185_CR16","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1097\/QAI.0000000000000476","volume":"68","author":"FA Post","year":"2015","unstructured":"Post FA, Winston J, Andrade-Villanueva JF, et al. Elvitegravir\/cobicistat\/emtricitabine\/ tenofovir DF in HIV-infected patients with mild-to-moderate renal impairment. J Acquir Immune Defic Syndr. 2015;68:310\u20133.","journal-title":"J Acquir Immune Defic Syndr"},{"key":"185_CR17","doi-asserted-by":"publisher","first-page":"1004.e9","DOI":"10.1016\/j.cmi.2016.08.012","volume":"22","author":"A Gonzalez-Serna","year":"2016","unstructured":"Gonzalez-Serna A, Swenson LC, Watson B, Auyeung K, Montaner J, Harrigan R. A single untimed plasma drug concentration measurement during low-level HIV viremia predicts virologic failure. Clin Microbiol Infection. 2016;22:1004.e9\u201316.","journal-title":"Clin Microbiol Infection"},{"key":"185_CR18","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1097\/QAD.0000000000000544","volume":"29","author":"The Antiretroviral Therapy Cohort Collaboration","year":"2015","unstructured":"The Antiretroviral Therapy Cohort Collaboration. (ART-CC). Impact of low-level viremia on clinical and virological outcomes in treated HIV-1-infected patients. AIDS. 2015;29:373\u201383.","journal-title":"AIDS"},{"key":"185_CR19","unstructured":"Panel on antiretroviral guidelines for adults and adolescents. Guideleins for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. http:\/\/www.aidsinfo.nih.gov\/ContentFiles\/AdultandAdolescentGL.pdf. Accessed 13 Oct 2017."},{"issue":"2","key":"185_CR20","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1001\/jama.2016.8900","volume":"316","author":"HF G\u00fcnthard","year":"2016","unstructured":"G\u00fcnthard HF, Saag MS, Benson CA, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2016 recommendations of the international antiviral society-USA Panel. JAMA. J Am Med Assoc. 2016;316(2):191\u2013210.","journal-title":"J Am Med Assoc"},{"key":"185_CR21","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1097\/QAI.0b013e31819e721b","volume":"51","author":"V Lima","year":"2009","unstructured":"Lima V, Harrigan R, Montaner JS. Increased reporting of detectable plasma HIV-1 RNA levels at the critical threshold of 50 copies per milliliter with the Taqman assay in comparison to the Amplicor assay. J Acquir Immune Defic Syndr. 2009;51:3\u20136.","journal-title":"J Acquir Immune Defic Syndr"},{"key":"185_CR22","unstructured":"Sekar V, Vanden Abeele C, Van Baelen B, et al. Pharmacokinetic\/pharmacodynamic analyses of once-daily darunavir in the ARTEMIS study. 15th Conference on Retroviruses and Opportunistic Infections. February 3\u20136, 2008. Boston, USA. (poster 769)."},{"key":"185_CR23","doi-asserted-by":"publisher","first-page":"443","DOI":"10.3851\/IMP2722","volume":"19","author":"A Gutierrez-Valencia","year":"2014","unstructured":"Gutierrez-Valencia A, Torres-Cornejo A, BenMarzouk-Hidalgo OJ, et al. Darunavir minimum plasma concentration and ritonavir-boosted darunavir monotherapy outcome in HIV-infected patients. Antivir Ther. 2014;19:443\u20137.","journal-title":"Antivir Ther"},{"key":"185_CR24","first-page":"816","volume":"72","author":"A Gutierrez-Valencia","year":"2017","unstructured":"Gutierrez-Valencia A, Benmarzouk-Hidalgo OJ, Llaves S, et al. Pharmacokinetic interactions between cobicistat-boosted elvitegravir and darunavir in HIV-infected patients. J Antimicrob Chemother. 2017;72:816\u20139.","journal-title":"J Antimicrob Chemother"},{"key":"185_CR25","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/1742-6405-11-39","volume":"11","author":"K Tashima","year":"2014","unstructured":"Tashima K, Crofoot G, Tomaka FL, et al. Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a Phase IIIb, open-label single-arm trial. AIDS Res Ther. 2014;11:39.","journal-title":"AIDS Res Ther"},{"key":"185_CR26","unstructured":"Ramanathan S, Wei X, Szwarcberg J, Chang S, Cheng AK, Kearney BP. Exposure-response analysis of once-daily elvitegravir administered as EVG\/COBI\/FTC\/TDF single tablet regimen (Quad STR) in HIV-1 infected patients. In: 19th Conference on Retroviruses and Opportunistic Infections. March 5\u20138, 2012. Seattle, USA. (poster 622)."},{"key":"185_CR27","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1002\/jcph.290","volume":"54","author":"TN Kakuda","year":"2014","unstructured":"Kakuda TN, Opsomer M, Timmers M, et al. Pharmacokinetics of darunavir in fixed-dose combination with cobicistat compared with coadministration of darunavir and ritonavir as single agents in healthy volunteers. J Clin Pharm. 2014;54:949\u201357.","journal-title":"J Clin Pharm."},{"issue":"5","key":"185_CR28","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1097\/QAI.0b013e3182364c67","volume":"58","author":"A Jackson","year":"2011","unstructured":"Jackson A, Watson V, Back D, et al. Plasma and Intracellular Pharmacokinetics of darunavir\/ritonavir once daily and raltegravir once and twice daily in HIV-1 infected individuals. J Acquir Immune Defic Syndr. 2011;58(5):450\u20137.","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"2","key":"185_CR29","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3851\/IMP1517","volume":"15","author":"L Garvey","year":"2010","unstructured":"Garvey L, Latc N, Erlwein OW, et al. The effects of a nucleoside-sparing antiretroviral regimen on the pharmacokinetics of ritonavir-boosted darunavir in HIV type-1-infected patients. Antivir Ther. 2010;15(2):213\u20138.","journal-title":"Antivir Ther"},{"issue":"2","key":"185_CR30","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1177\/0091270010371113","volume":"51","author":"I Song","year":"2011","unstructured":"Song I, Min SS, Borland J, et al. The effect of lopinavir\/ritonavir and darunavir\/ritonavir on the HIV integrase inhibitor S\/GSK1349572 in healthy participants. J Clin Pharmacol. 2011;51(2):237\u201342.","journal-title":"J Clin Pharmacol"},{"key":"185_CR31","doi-asserted-by":"publisher","first-page":"2314","DOI":"10.1128\/AAC.49.6.2314-2321.2005","volume":"49","author":"S De Meyer","year":"2005","unstructured":"De Meyer S, Azijn H, Surleraux D, et al. TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. Antimicrob Agents Chemother. 2005;49:2314\u201321.","journal-title":"Antimicrob Agents Chemother"},{"key":"185_CR32","unstructured":"S Ramanathan, H Wang, T Stondell, A Cheng, and BP Kearney. Pharmacokinetics and Drug Interaction Profile of Cobicistat boosted-Elvitegravir with Atazanavir, Rosuvastatin or Rifabutin. In: 13th International Workshop on Clinical Pharmacology of HIV Therapy, Barcelona, Spain. April 16\u201318, 2012."},{"key":"185_CR33","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.ijpharm.2016.08.063","volume":"512","author":"D Cattaneo","year":"2016","unstructured":"Cattaneo D, Baldelli S, Minisci D, et al. When food can make the difference: the case of elvitegravir-based co-formulation. Int J Pharm. 2016;512:301\u20134.","journal-title":"Int J Pharm"},{"issue":"4","key":"185_CR34","doi-asserted-by":"publisher","first-page":"229","DOI":"10.2165\/11584570-000000000-00000","volume":"50","author":"S Ramanathan","year":"2011","unstructured":"Ramanathan S, Mathias AA, German P, Kearney BP. Clinical pharmacokinetic and pharmacodynamic profile of the HIV integrase inhibitor elvitegravir. Clin Pharmacokinet. 2011;50(4):229\u201344.","journal-title":"Clin Pharmacokinet"},{"key":"185_CR35","doi-asserted-by":"publisher","first-page":"1933","DOI":"10.1093\/jac\/dkw050","volume":"71","author":"C Barcelo","year":"2016","unstructured":"Barcelo C, Gaspar F, Aouri M, et al. Population pharmacokinetic analysis of elvitegravir and cobicistat in HIV-1-infected individuals. J Antimicrob Chemother. 2016;71:1933\u201342.","journal-title":"J Antimicrob Chemother"},{"key":"185_CR36","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1097\/QAI.0000000000001193","volume":"74","author":"GD Huhn","year":"2017","unstructured":"Huhn GD, Tebas P, Gallant J, et al. A randomized, open-label trial to evaluate switching to elvitegravir\/cobicistat\/emtricitabine\/tenofovir alafenamide plus darunavir in treatment-experienced HIV-1-infected adults. J Acquir Immune Defic Syndr. 2017;74:193\u2013200.","journal-title":"J Acquir Immune Defic Syndr"},{"key":"185_CR37","unstructured":"Gilead Sciences Canada Inc. Genvoya Product Monograph. Mississauga, Ontario, Canada; May 24, 2017."}],"container-title":["AIDS Research and Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12981-017-0185-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12981-017-0185-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12981-017-0185-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T17:12:48Z","timestamp":1628615568000},"score":1,"resource":{"primary":{"URL":"https:\/\/aidsrestherapy.biomedcentral.com\/articles\/10.1186\/s12981-017-0185-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,2]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["185"],"URL":"https:\/\/doi.org\/10.1186\/s12981-017-0185-4","relation":{},"ISSN":["1742-6405"],"issn-type":[{"value":"1742-6405","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,2]]},"assertion":[{"value":"28 August 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 October 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 November 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"59"}}