{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T14:13:51Z","timestamp":1768313631799,"version":"3.49.0"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,2,18]],"date-time":"2014-02-18T00:00:00Z","timestamp":1392681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:p>Whether hormonal contraceptives increase <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u20101 acquisition, transmission and disease progression are critical questions. Clinical research has been hampered by a lack of understanding that different progestins used in contraception exhibit differential off\u2010target effects via steroid receptors other than the progesterone receptor. Of particular, relevance is the relative effects of medroxyprogesterone acetate (<jats:styled-content style=\"fixed-case\">MPA<\/jats:styled-content>) and norethisterone enanthate (<jats:styled-content style=\"fixed-case\">NET<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">EN<\/jats:styled-content>), widely used as injectable contraceptives in sub\u2010Saharan Africa. While most high\u2010quality clinical studies find no increased risk for <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u20101 acquisition with oral contraception or injectable <jats:styled-content style=\"fixed-case\">NET<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">EN<\/jats:styled-content>, most do find an increase with <jats:styled-content style=\"fixed-case\">MPA<\/jats:styled-content>, particularly in young women. Furthermore, mounting evidence from animal, <jats:italic>ex vivo<\/jats:italic> and biochemical studies are consistent with <jats:styled-content style=\"fixed-case\">MPA<\/jats:styled-content> acting to increase <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u20101 acquisition and pathogenesis, via mechanisms involving glucocorticoid\u2010like effects on gene expression, in particular genes involved in immune function. We report that <jats:styled-content style=\"fixed-case\">MPA<\/jats:styled-content>, unlike <jats:styled-content style=\"fixed-case\">NET<\/jats:styled-content> and progesterone, represses inflammatory genes in human <jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content>s in a dose\u2010dependent manner, via the glucocorticoid receptor (<jats:styled-content style=\"fixed-case\">GR<\/jats:styled-content>), at concentrations within the physiologically relevant range. These and published results collectively suggest that the differential <jats:styled-content style=\"fixed-case\">GR<\/jats:styled-content> activity of <jats:styled-content style=\"fixed-case\">MPA<\/jats:styled-content> versus <jats:styled-content style=\"fixed-case\">NET<\/jats:styled-content> may be a mechanism whereby <jats:styled-content style=\"fixed-case\">MPA<\/jats:styled-content>, unlike <jats:styled-content style=\"fixed-case\">NET<\/jats:styled-content> or progesterone, differentially modulates <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u20101 acquisition and pathogenesis in target cells where the <jats:styled-content style=\"fixed-case\">GR<\/jats:styled-content> is the predominant steroid receptor expressed.<\/jats:p>","DOI":"10.1111\/aji.12214","type":"journal-article","created":{"date-parts":[[2014,2,18]],"date-time":"2014-02-18T12:55:53Z","timestamp":1392728153000},"page":"505-512","source":"Crossref","is-referenced-by-count":30,"title":["Differential Glucocorticoid Receptor\u2010Mediated Effects on Immunomodulatory Gene Expression by Progestin Contraceptives: Implications for <scp>HIV<\/scp>\u20101 Pathogenesis"],"prefix":"10.1111","volume":"71","author":[{"given":"Janet P.","family":"Hapgood","sequence":"first","affiliation":[{"name":"Department of Molecular and Cell Biology University of Cape Town Rondebosch South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roslyn M.","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology University of Cape Town Rondebosch South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yashini","family":"Govender","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology University of Cape Town Rondebosch South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chanel","family":"Avenant","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology University of Cape Town Rondebosch South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Tomasicchio","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology University of Cape Town Rondebosch South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,2,18]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"WHO:Hormonal Contraception and HIV: Technical Statement.2012. 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