{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:14:29Z","timestamp":1772118869227,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,3,22]],"date-time":"2019-03-22T00:00:00Z","timestamp":1553212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2019,4]]},"abstract":"\n Study Objective<\/jats:title>\n \n Dual therapy with once\/day dolutegravir (\n DTG<\/jats:styled-content>\n ) plus boosted darunavir (\n DRV<\/jats:styled-content>\n \/b) may be a suitable and effective strategy with a high genetic barrier to resistance in patients infected with human immunodeficiency virus (\n HIV<\/jats:styled-content>\n ). Our aim was to evaluate the effectiveness of\n DTG<\/jats:styled-content>\n plus\n DRV<\/jats:styled-content>\n \/b (\n DTG<\/jats:styled-content>\n +\n DRV<\/jats:styled-content>\n \/b) as a switch strategy in\n HIV<\/jats:styled-content>\n \u2010infected patients, irrespective of their history of virologic failure (\n VF<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n Multicenter retrospective cohort study.<\/jats:p>\n <\/jats:sec>\n \n Setting<\/jats:title>\n \n Human immunodeficiency<\/jats:styled-content>\n outpatient treatment clinics at three university hospitals in Spain.\n <\/jats:p>\n <\/jats:sec>\n \n Patients<\/jats:title>\n \n Fifty\n HIV<\/jats:styled-content>\n \u2010infected adults who had a stable antiretroviral treatment (\n ART<\/jats:styled-content>\n ) regimen and an undetectable viral load for at least 6\u00a0months, and whose\n ART<\/jats:styled-content>\n was switched to once\/day\n DTG<\/jats:styled-content>\n +\n DRV<\/jats:styled-content>\n \/b between January 2015 and January 2018 were included in the analysis. Historical genotype at the time of\n VF<\/jats:styled-content>\n was available in 44 patients.\n <\/jats:p>\n <\/jats:sec>\n \n Measurements and Main Results<\/jats:title>\n \n Patients were followed until\n VF<\/jats:styled-content>\n or treatment discontinuation for any reason. The primary outcome was the percentage of patients with a viral load of 50 copies\/mL or lower at the last follow\u2010up visit. Secondary outcomes included changes in\n CD<\/jats:styled-content>\n 4\n +<\/jats:sup>\n cell count, lipid profile, and renal function. Of the 50 patients included, median time of viral suppression was 52 months (interquartile range [IQR] 18\u2013103 mo) and nadir\n CD<\/jats:styled-content>\n 4\n +<\/jats:sup>\n 89 cells\/mm\n 3<\/jats:sup>\n (IQR 37\u2013241 cells\/mm\n 3<\/jats:sup>\n ). Patients had a history of a median of 8\n ART<\/jats:styled-content>\n combinations (IQR 4\u201311 combinations) and 3 VFs (IQR 2\u20138 VFs). The historical genotypes from 44 patients showed 41 patients (93.2%) with nucleoside\/nucleotide reverse transcriptase inhibitor (\n NRTI<\/jats:styled-content>\n ) resistance\u2010associated mutations (\n RAM<\/jats:styled-content>\n s), 32 (72.7%) with nonnucleoside reverse transcriptase inhibitor (\n NNRTI<\/jats:styled-content>\n )\n RAM<\/jats:styled-content>\n s, and 12 (27.3%) with primary protease inhibitor (\n PI<\/jats:styled-content>\n )\n RAM<\/jats:styled-content>\n s; 7 (15.9%) had darunavir\n RAM<\/jats:styled-content>\n s, and no patients had baseline integrase strand transfer inhibitor\n RAM<\/jats:styled-content>\n s. Thirty\u2010seven patients (84.1%) had resistance to at least two antiretroviral classes. After a median of 25 months (IQR 17\u201328 mo) of follow\u2010up, 49 patients (98%) maintained a viral load of 50 copies\/\n mL or lower<\/jats:styled-content>\n , and 1 patient (2%) had\n VF<\/jats:styled-content>\n . No new\n RAM<\/jats:styled-content>\n s emerged at\n VF<\/jats:styled-content>\n . At week 4, serum creatinine concentration increased a median of 0.12 mg\/dl (0.03\u20130.23 mg\/\n dl)<\/jats:styled-content>\n . At last visit, total cholesterol and low\u2010density lipoprotein cholesterol levels increased by a median of 9 mg\/\n dl<\/jats:styled-content>\n (IQR \u221218 to 40 mg\/\n dl<\/jats:styled-content>\n ) and 16 mg\/\n dl<\/jats:styled-content>\n (IQR \u22129 to 40 mg\/\n dl<\/jats:styled-content>\n ), respectively, whereas\n CD<\/jats:styled-content>\n 4\n +<\/jats:sup>\n cell count remained stable (median +13 cell\/mm\n 3<\/jats:sup>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n In this cohort of heavily treated\n HIV<\/jats:styled-content>\n \u2010infected patients with virologic suppression, switching to the combination of\n DTG<\/jats:styled-content>\n +\n DRV<\/jats:styled-content>\n \/b was a convenient regimen that was highly effective and had good tolerability.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/phar.2227","type":"journal-article","created":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T23:15:58Z","timestamp":1549408558000},"page":"501-507","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Effectiveness of Once\/Day Dolutegravir Plus Boosted Darunavir as a Switch Strategy in Heavily Treated Patients with Human Immunodeficiency Virus"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7187-0367","authenticated-orcid":false,"given":"Jordi","family":"Navarro","sequence":"first","affiliation":[{"name":"Infectious Diseases Department Vall d'Hebron University Hospital Barcelona Spain"},{"name":"Vall d'Hebron Research Institute Barcelona Spain"},{"name":"Medicine Department Autonomous University of Barcelona Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Ram\u00f3n","family":"Santos","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3 Lluita contra la Sida University Hospital Germans Trias i Pujol Badalona Spain"},{"name":"Infectious Diseases Department University Hospital Germans Trias i Pujol Badalona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Silva","sequence":"additional","affiliation":[{"name":"HIV and STI Unit Infectious Diseases Department Bellvitge University Hospital\u2010IDIBELL L'Hospitalet de Llobregrat Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joaquin","family":"Burgos","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department Vall d'Hebron University Hospital Barcelona Spain"},{"name":"Vall d'Hebron Research Institute Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicen\u00e7","family":"Falc\u00f3","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department Vall d'Hebron University Hospital Barcelona Spain"},{"name":"Vall d'Hebron Research Institute Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esteban","family":"Ribera","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department Vall d'Hebron University Hospital Barcelona Spain"},{"name":"Vall d'Hebron Research Institute Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arkaitz","family":"Imaz","sequence":"additional","affiliation":[{"name":"HIV and STI Unit Infectious Diseases Department Bellvitge University Hospital\u2010IDIBELL L'Hospitalet de Llobregrat Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Curran","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department Vall d'Hebron University Hospital Barcelona Spain"},{"name":"Vall d'Hebron Research Institute Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,3,22]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"Guidelines for the use of antiretroviral agents in HIV\u20101\u2010infected adults and adolescents","author":"Panel\u00a0on Antiretroviral Guidelines for Adults and Adolescents"},{"key":"e_1_2_7_3_1","unstructured":"European AIDS Clinical Society (EACS).Guidelines for the clinical management and treatment of HIV\u2010infected adults. 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