{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:57:12Z","timestamp":1777453032905,"version":"3.51.4"},"reference-count":44,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cobicistat (COBI), a CYP3A inhibitor, is a pharmacokinetic enhancer that increases exposures of the HIV protease inhibitors (PIs) atazanavir (ATV) and darunavir (DRV). The potential drug interaction between COBI-boosted PIs and hormonal contraceptives, which are substrates of intestinal efflux transporters and extensively metabolized by CYP enzymes, glucuronidation and sulfation, was evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a Phase I, open-label, two cohort ( n=18\/cohort), fixed-sequence study in healthy females that evaluated the drug\u2013drug interaction (DDI) between multiple-dose ATV+COBI or DRV+COBI and single-dose drospirenone\/ethinyl estradiol (EE). DDIs were evaluated using 90% confidence intervals of the geometric least-squares mean ratios of the test (drospirenone\/EE+boosted PI) versus reference (drospirenone\/EE) using lack of DDI boundaries of 70\u2013143%. Safety was assessed throughout the study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      29\/36 participants completed the study. Relative to drospirenone\/EE alone, drospirenone area under the plasma concentration versus time curve extrapolated to infinity (AUC\n                      <jats:sub>inf<\/jats:sub>\n                      ) was 1.6-fold and 2.3-fold higher, and maximum observed plasma concentration (C\n                      <jats:sub>max<\/jats:sub>\n                      ) was unaltered, upon coadministration with DRV+COBI and ATV+COBI, respectively. EE AUC\n                      <jats:sub>inf<\/jats:sub>\n                      decreased 30% with drospirenone\/EE + DRV+COBI and was unchanged with ATV+COBI + drospirenone\/EE, relative to drospirenone\/EE alone. Study treatments were generally well tolerated. The majority of adverse events were mild and consistent with known safety profiles of the compounds.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Consistent with COBI-mediated CYP3A inhibition, drospirenone exposure increased following coadministration with COBI-containing regimens, with a greater increase with ATV+COBI. Thus, clinical monitoring for drospirenone-associated hyperkalaemia is recommended with DRV+COBI and ATV+COBI should not be used with drospirenone. Lower EE exposure with DRV+COBI may be attributed to inductive effects of DRV on CYP enzymes and\/or intestinal efflux transporters (that is, P-gp) involved in EE disposition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp3343","type":"journal-article","created":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T06:41:42Z","timestamp":1578984102000},"page":"557-566","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Confirmation of the Drug\u2013drug Interaction Potential between Cobicistat-boosted Antiretroviral Regimens and Hormonal Contraceptives"],"prefix":"10.1177","volume":"24","author":[{"given":"Sophia R","family":"Majeed","sequence":"first","affiliation":[{"name":"Gilead Sciences, Foster City, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"West","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kah Hiing","family":"Ling","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moupali","family":"Das","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian P","family":"Kearney","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Foster City, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2018,11,1]]},"reference":[{"key":"bibr1-IMP3343","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2013.772579"},{"key":"bibr2-IMP3343","unstructured":"World Health Organization. HIV\/AIDS data and statistics. (Accessed 14 August 2018.) Available from http:\/\/www.who.int\/hiv\/data\/en\/."},{"key":"bibr3-IMP3343","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000001392"},{"key":"bibr4-IMP3343","unstructured":"Panel on Antiretroviral Guidelines for Adult and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. (Updated 25 October 2018. Accessed 20 June 2019.) Available from https:\/\/aidsinfo.nih.gov\/guidelines\/html\/1\/adult-and-adolescent-arv\/0."},{"key":"bibr5-IMP3343","unstructured":"World Health Organization. Contraceptive eligibility for women at high risk of HIV. (Updated 2017. Accessed 20 June 2019.) Available from https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/326653\/9789241550574-eng.pdf?ua=1."},{"key":"bibr6-IMP3343","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200746020-00003"},{"key":"bibr7-IMP3343","volume-title":"Package insert","author":"Reyataz\u00ae (atazanavir sulfate).","year":"2018"},{"key":"bibr8-IMP3343","volume-title":"Package insert","year":"2018"},{"key":"bibr9-IMP3343","volume-title":"Package insert","year":"2018"},{"key":"bibr10-IMP3343","unstructured":"Stribild\u00ae (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate). Package insert. Revised November 2018. Gilead Sciences, Foster City, CA, USA."},{"key":"bibr11-IMP3343","unstructured":"German P., Wang M., Warren D., Kearney B.P. Pharmacokinetic interaction between norgestimate\/ethinyl estradiol and EVG\/COBI\/FTC\/TDF single tablet regimen.\n                      12th International Workshop on Clinical Pharmacology of HIV Therapy.\n                      13\u201315 April 2011, Miami, FL, USA. Abstract O_17."},{"key":"bibr12-IMP3343","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.637"},{"key":"bibr13-IMP3343","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-014-0204-8"},{"key":"bibr14-IMP3343","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-014-1711-0"},{"key":"bibr15-IMP3343","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2015.03.006"},{"key":"bibr16-IMP3343","volume-title":"Package insert.","author":"Yaz\u00ae (drospirenone\/ethinyl estradiol)."},{"key":"bibr17-IMP3343","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12745"},{"key":"bibr18-IMP3343","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2007.03084.x"},{"key":"bibr19-IMP3343","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12499"},{"key":"bibr20-IMP3343","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.346"},{"key":"bibr21-IMP3343","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2005.10105.x"},{"key":"bibr22-IMP3343","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-016-0452-7"},{"key":"bibr23-IMP3343","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-23375-6"},{"key":"bibr24-IMP3343","doi-asserted-by":"publisher","DOI":"10.1177\/1060028017717018"},{"key":"bibr25-IMP3343","volume-title":"Package insert","author":"Tybost\u00ae (cobicistat).","year":"2018"},{"key":"bibr26-IMP3343","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e3182645648"},{"key":"bibr27-IMP3343","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq324"},{"key":"bibr28-IMP3343","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00486-13"},{"key":"bibr29-IMP3343","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e3181f52f0c"},{"key":"bibr30-IMP3343","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.256"},{"key":"bibr31-IMP3343","unstructured":"Custodio J.M., West S.K., Sengupta D. Evaluation of the drug-drug interaction (DDI) potential between cobicistat-boosted protease inhibitors and statins.\n                      International Workshop on Clinical Pharmacology of Antiviral Therapy.\n                      14\u201316 June 2017, Chicago, IL, USA. Abstract Oral #4."},{"key":"bibr32-IMP3343","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy201"},{"key":"bibr33-IMP3343","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2007.03084.x"},{"key":"bibr34-IMP3343","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1724"},{"key":"bibr35-IMP3343","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2003.02015.x"},{"key":"bibr36-IMP3343","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e3181eb5ff5"},{"key":"bibr37-IMP3343","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12668"},{"key":"bibr38-IMP3343","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2009.228"},{"key":"bibr39-IMP3343","volume-title":"Summary of Product Characteristics.","author":"Tybost\u00ae (cobicistat)."},{"key":"bibr40-IMP3343","volume-title":"Package insert","author":"Norvir\u00ae (Ritonavir).","year":"2017"},{"key":"bibr41-IMP3343","doi-asserted-by":"publisher","DOI":"10.2217\/WHE.10.36"},{"key":"bibr42-IMP3343","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-016-0452-7"},{"key":"bibr43-IMP3343","doi-asserted-by":"publisher","DOI":"10.1089\/apc.2013.0009"},{"key":"bibr44-IMP3343","volume-title":"Summary of Product Characteristics.","author":"Yasmin\u00ae (drospirenone\/ethinyl estradiol).","year":"2018"}],"container-title":["Antiviral Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP3343","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3851\/IMP3343","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP3343","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:52:50Z","timestamp":1777380770000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3851\/IMP3343"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,1]]},"references-count":44,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2019,11]]}},"alternative-id":["10.3851\/IMP3343"],"URL":"https:\/\/doi.org\/10.3851\/imp3343","relation":{},"ISSN":["1359-6535","2040-2058"],"issn-type":[{"value":"1359-6535","type":"print"},{"value":"2040-2058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,1]]}}}