{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T07:02:51Z","timestamp":1777532571081,"version":"3.51.4"},"reference-count":16,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T00:00:00Z","timestamp":1552521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Janssen Scientific Affairs, LLC"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HIV Medicine"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>The aim of the study was to evaluate darunavir and cobicistat pharmacokinetics in pregnant women with <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u20101 infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This phase 3b, open\u2010label study enrolled <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u20101\u2010infected pregnant women (18\u201326\u00a0weeks of gestation) receiving combination antiretroviral therapy with once\u2010daily darunavir\/cobicistat 800\/150\u00a0mg. The plasma pharmacokinetics of darunavir (total and unbound) and cobicistat were assessed over 24\u00a0h during the second and third trimesters (24\u201328 and 34\u201338\u00a0weeks of gestation, respectively) and 6\u201312\u00a0weeks postpartum. Pharmacokinetic parameters [area under the plasma concentration\u2013time curve over 24\u00a0h (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>24\u00a0h<\/jats:sub>), maximum plasma concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) and minimum plasma concentration (<jats:italic>C<\/jats:italic><jats:sub>min<\/jats:sub>)] were derived using noncompartmental analysis and compared using linear mixed effects modelling (pregnancy versus postpartum). Antiviral activity and safety were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seven women were enrolled in the study; six completed it. Total darunavir exposure was lower during pregnancy than postpartum (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>24\u00a0h<\/jats:sub>, 50\u201356% lower; <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>, 37\u201349% lower; <jats:italic>C<\/jats:italic><jats:sub>min<\/jats:sub>, 89\u201392% lower); unbound darunavir exposure was also reduced (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>24\u00a0h<\/jats:sub>, 40\u201345% lower; <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>, 32\u201341% lower; <jats:italic>C<\/jats:italic><jats:sub>min<\/jats:sub>, 88\u201392% lower). Cobicistat exposure was also lower during pregnancy than postpartum (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>24\u00a0h<\/jats:sub>, 49\u201363% lower; <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>, 27\u201350% lower; <jats:italic>C<\/jats:italic><jats:sub>min<\/jats:sub>, 83% lower). At study completion, five of six (83%) women were virologically suppressed (<jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u20101 <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> &lt;\u00a050 copies\/<jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content>). There was one virological failure (the patient was nonadherent; no emerging genotypic resistance was observed and susceptibility to antiretrovirals was maintained). No mother\u2010to\u2010child transmission was detected among six infants born to the six women who completed the study. Overall, darunavir\/cobicistat was well tolerated in women and infants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In view of markedly reduced darunavir and cobicistat exposures during pregnancy, this combination is not recommended in <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u20101\u2010infected pregnant women.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hiv.12721","type":"journal-article","created":{"date-parts":[[2019,3,15]],"date-time":"2019-03-15T05:29:06Z","timestamp":1552627746000},"page":"337-343","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Reduced exposure to darunavir and cobicistat in <scp>HIV<\/scp>\u20101\u2010infected pregnant women receiving a darunavir\/cobicistat\u2010based regimen"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4516-8830","authenticated-orcid":false,"given":"HM","family":"Crauwels","sequence":"first","affiliation":[{"name":"Janssen Research &amp; Development Beerse Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O","family":"Osiyemi","sequence":"additional","affiliation":[{"name":"Triple O Research Institute PA West Palm Beach FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Zorrilla","sequence":"additional","affiliation":[{"name":"University of Puerto Rico School of Medicine San Juan Puerto Rico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Bicer","sequence":"additional","affiliation":[{"name":"BICER Consulting &amp; Research Antwerp Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Brown","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC Titusville NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,3,14]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"Panel\u00a0on treatment of pregnant women with HIV infection and prevention of perinatal transmission. Recommendations for use of antiretroviral drugs in transmission in the United States. Available athttps:\/\/aidsinfo.nih.gov\/contentfiles\/lvguidelines\/PerinatalGL.pdf(accessed 13 June 2018)."},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200544100-00001"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1293.2012.01060.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/15284336.2017.1387690"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.290"},{"key":"e_1_2_7_7_1","first-page":"16","article-title":"Pharmacokinetics and safety of darunavir\/ritonavir in HIV\u2010infected pregnant women","volume":"19","author":"Khoo S","year":"2017","journal-title":"AIDS Rev"},{"key":"e_1_2_7_8_1","unstructured":"European AIDS Clinical Society.EACS Guidelines version 9.0 October2017."},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/hiv.12047"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/hiv.12366"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000001068"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-017-0184-8"},{"key":"e_1_2_7_13_1","unstructured":"PREZCOBIX\u00ae(darunavir and cobicistat) [package insert].\u00a0Titusville NJ: Janssen Therapeutics; June2018."},{"key":"e_1_2_7_14_1","unstructured":"BestBM CapparelliEV StekAet\u00a0al.Elvitegravir\/cobicistat pharmacokinetics in pregnancy and postpartum.7th International Workshop on HIV & Women. Seattle WA 11\u201312 February 2017. Oral presentation #6."},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000001755"},{"key":"e_1_2_7_16_1","unstructured":"MomperJD BestB WangJet\u00a0al.Pharmacokinetics of darunavir boosted with cobicistat during pregnancy and postpartum.22nd International AIDS Conference. Amsterdam the Netherlands 23\u201327 July 2018. Poster WEPEB118."},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.2015.1033400"}],"container-title":["HIV Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhiv.12721","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hiv.12721","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hiv.12721","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hiv.12721","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T01:20:52Z","timestamp":1724894452000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hiv.12721"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,14]]},"references-count":16,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1111\/hiv.12721"],"URL":"https:\/\/doi.org\/10.1111\/hiv.12721","archive":["Portico"],"relation":{},"ISSN":["1464-2662","1468-1293"],"issn-type":[{"value":"1464-2662","type":"print"},{"value":"1468-1293","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,14]]},"assertion":[{"value":"2019-01-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}