{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:12:03Z","timestamp":1790471523326,"version":"4.1.0"},"reference-count":122,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,3,13]],"date-time":"2019-03-13T00:00:00Z","timestamp":1552435200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,3,13]],"date-time":"2019-03-13T00:00:00Z","timestamp":1552435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009633","name":"U.S. Department of Health &amp; Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD083026"],"award-info":[{"award-number":["R01HD083026"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The intramuscular progestin-only injectable contraceptive, depo-medroxyprogesterone acetate (DMPA-IM), is more widely used in Sub-Saharan Africa than another injectable contraceptive, norethisterone enanthate (NET-EN). Epidemiological data show a significant 1.4-fold increased risk of HIV-1 acquisition for DMPA-IM usage, while no such association is shown from limited data for NET-EN. We show that MPA, unlike NET, significantly increases R5-tropic but not X4-tropic HIV-1 replication <jats:italic>ex vivo<\/jats:italic> in human endocervical and ectocervical explant tissue from pre-menopausal donors, at physiologically relevant doses. Results support a mechanism whereby MPA, unlike NET, acts via the glucocorticoid receptor (GR) to increase HIV-1 replication in cervical tissue by increasing the relative frequency of CD4+ T cells and activated monocytes. We show that MPA, unlike NET, increases mRNA expression of the CD4 HIV-1 receptor and CCR5 but not CXCR4 chemokine receptors, via the GR. However, increased density of CD4 on CD3+ cells was not observed with MPA by flow cytometry of digested tissue. Results suggest that DMPA-IM may increase HIV-1 acquisition <jats:italic>in vivo<\/jats:italic> at least in part via direct effects on cervical tissue to increase founder R5-tropic HIV-1 replication. Our findings support differential biological mechanisms and disaggregation of DMPA-IM and NET-EN regarding HIV-1 acquisition risk category for use in high risk areas.<\/jats:p>","DOI":"10.1038\/s41598-019-40756-7","type":"journal-article","created":{"date-parts":[[2019,3,13]],"date-time":"2019-03-13T11:02:46Z","timestamp":1552474966000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["The contraceptive medroxyprogesterone acetate, unlike norethisterone, directly increases R5 HIV-1 infection in human cervical explant tissue at physiologically relevant concentrations"],"prefix":"10.1038","volume":"9","author":[{"given":"Roslyn M.","family":"Ray","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle F.","family":"Maritz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanel","family":"Avenant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Tomasicchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigcinile","family":"Dlamini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zephne","family":"van der Spuy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet P.","family":"Hapgood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,13]]},"reference":[{"key":"40756_CR1","unstructured":"GBD 2015 HIV Collaborators. Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980\u20132015: the Global Burden of Disease Study 2015. Lancet HIV 3, e361\u2013387 (2016)."},{"key":"40756_CR2","unstructured":"Joint United Nationals Programme on HIV\/AIDS (UNAIDS). Fact sheet 2016. Available at: http:\/\/www.unaids.org\/sites\/default\/files\/media_asset\/20150901_FactSheet_2015_en.pdf."},{"key":"40756_CR3","unstructured":"Darroch, J. E., Singh, S. & Weissman, E. Adding It Up: The Costs and Benefits of Investing in Family Planning and Maternal and Newborn Health 2014 - Estimation Methodology. (New York: Guttmacher Institute, 2016)."},{"key":"40756_CR4","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1097\/QAD.0b013e32835a5a52","volume":"27","author":"AR Butler","year":"2013","unstructured":"Butler, A. R. et al. Modelling the global competing risks of a potential interaction between injectable hormonal contraception and HIV risk. AIDS 27, 105\u2013113 (2013).","journal-title":"AIDS"},{"key":"40756_CR5","doi-asserted-by":"publisher","first-page":"2665","DOI":"10.1097\/QAD.0000000000001228","volume":"30","author":"CB Polis","year":"2016","unstructured":"Polis, C. B. et al. An updated systematic review of epidemiological evidence on hormonal contraceptive methods and HIV acquisition in women. AIDS 30, 2665\u20132683 (2016).","journal-title":"AIDS"},{"key":"40756_CR6","doi-asserted-by":"publisher","first-page":"e1001778","DOI":"10.1371\/journal.pmed.1001778","volume":"12","author":"CS Morrison","year":"2015","unstructured":"Morrison, C. S. et al. Hormonal contraception and the risk of HIV acquisition: an individual participant data meta-analysis. PLoS Med. 12, e1001778 (2015).","journal-title":"PLoS Med."},{"key":"40756_CR7","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1097\/GCO.0000000000000228","volume":"27","author":"LJ Ralph","year":"2015","unstructured":"Ralph, L. J., Gollub, E. L. & Jones, H. E. Hormonal contraceptive use and women\u2019s risk of HIV acquisition: priorities emerging from recent data. Curr. Opin. Obstet. Gynecol. 27, 487\u2013495 (2015).","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"40756_CR8","doi-asserted-by":"publisher","first-page":"e279","DOI":"10.1016\/S2352-3018(15)00058-2","volume":"2","author":"LM Noguchi","year":"2015","unstructured":"Noguchi, L. M. et al. Risk of HIV-1 acquisition among women who use different types of injectable progestin contraception in South Africa: a prospective cohort study. Lancet HIV 2, e279\u2013287 (2015).","journal-title":"Lancet HIV"},{"key":"40756_CR9","unstructured":"World Health Organisation. Hormonal contraceptive eligibility for women at high risk of HIV. Guidance Statement: Recommendations concerning the use of hormonal contraceptive methods by women at high risk of HIV. (World Health Organisation, Geneva, Switzerland, 2017). Available at: http:\/\/www.who.int\/reproductivehealth\/publications\/family_planning\/HC-and-HIV-2017\/en\/ (2017)."},{"key":"40756_CR10","unstructured":"ECHO. The Evidence for Contraceptive Options and HIV Outcomes (ECHO) Study. Available at: http:\/\/echo-consortium.com\/ (2016)."},{"key":"40756_CR11","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.contraception.2017.12.003","volume":"97","author":"CB Polis","year":"2018","unstructured":"Polis, C. B., Achilles, S. L., Hel, Z. & Hapgood, J. P. Is a lower-dose, subcutaneous contraceptive injectable containing depot medroxyprogesterone acetate likely to impact women\u2019s risk of HIV? Contraception 97, 191\u2013197 (2018).","journal-title":"Contraception"},{"key":"40756_CR12","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1210\/er.2017-00103","volume":"39","author":"JP Hapgood","year":"2018","unstructured":"Hapgood, J. P., Kaushic, C. & Hel, Z. Hormonal Contraception and HIV-1 Acquisition: Biological Mechanisms. Endocr. Rev. 39, 36\u201378 (2018).","journal-title":"Endocr. Rev."},{"key":"40756_CR13","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/S1473-3099(15)00429-6","volume":"16","author":"EH Byrne","year":"2016","unstructured":"Byrne, E. H. et al. Association between injectable progestin-only contraceptives and HIV acquisition and HIV target cell frequency in the female genital tract in South African women: a prospective cohort study. Lancet Infect Dis 16, 441\u2013448 (2016).","journal-title":"Lancet Infect Dis"},{"key":"40756_CR14","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1093\/infdis\/jiv233","volume":"212","author":"G Sciaranghella","year":"2015","unstructured":"Sciaranghella, G. et al. CCR5 Expression Levels in HIV-Uninfected Women Receiving Hormonal Contraception. J. Infect. Dis. 212, 1397\u20131401 (2015).","journal-title":"J. Infect. Dis."},{"key":"40756_CR15","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1038\/mi.2016.22","volume":"9","author":"NE Quispe Calla","year":"2016","unstructured":"Quispe Calla, N. E. et al. Medroxyprogesterone acetate and levonorgestrel increase genital mucosal permeability and enhance susceptibility to genital herpes simplex virus type 2 infection. Mucosal Immunol 9, 1571\u20131583 (2016).","journal-title":"Mucosal Immunol"},{"key":"40756_CR16","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.jri.2015.03.007","volume":"110","author":"S Ngcapu","year":"2015","unstructured":"Ngcapu, S. et al. Lower concentrations of chemotactic cytokines and soluble innate factors in the lower female genital tract associated with the use of injectable hormonal contraceptive. J. Reprod. Immunol. 110, 14\u201321 (2015).","journal-title":"J. Reprod. Immunol."},{"key":"40756_CR17","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1097\/QAI.0000000000000531","volume":"68","author":"KG Michel","year":"2015","unstructured":"Michel, K. G., Huijbregts, R. P., Gleason, J. L., Richter, H. E. & Hel, Z. Effect of hormonal contraception on the function of plasmacytoid dendritic cells and distribution of immune cell populations in the female reproductive tract. J. Acquir. Immune Defic. Syndr. 68, 511\u2013518 (2015).","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"40756_CR18","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1111\/aji.12415","volume":"74","author":"J Deese","year":"2015","unstructured":"Deese, J. et al. Injectable Progestin-Only Contraception is Associated With Increased Levels of Pro-Inflammatory Cytokines in the Female Genital Tract. Am. J. Reprod. Immunol. 74, 357\u2013367 (2015).","journal-title":"Am. J. Reprod. Immunol."},{"key":"40756_CR19","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1097\/QAI.0000000000000103","volume":"66","author":"C Morrison","year":"2014","unstructured":"Morrison, C. et al. Cervical inflammation and immunity associated with hormonal contraception, pregnancy, and HIV-1 seroconversion. J. Acquir. Immune Defic. Syndr. 66, 109\u2013117 (2014).","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"40756_CR20","doi-asserted-by":"publisher","first-page":"e00221","DOI":"10.1128\/mBio.00221-15","volume":"6","author":"RN Fichorova","year":"2015","unstructured":"Fichorova, R. N. et al. The Contribution of Cervicovaginal Infections to the Immunomodulatory Effects of Hormonal Contraception. MBio 6, e00221\u201300215 (2015).","journal-title":"MBio"},{"key":"40756_CR21","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1177\/1933719114565035","volume":"22","author":"GA Goldfien","year":"2015","unstructured":"Goldfien, G. A. et al. Progestin-Containing Contraceptives Alter Expression of Host Defense-Related Genes of the Endometrium and Cervix. Reprod. Sci. 22, 814\u2013828 (2015).","journal-title":"Reprod. Sci."},{"key":"40756_CR22","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1016\/j.fertnstert.2007.01.046","volume":"90","author":"A Li","year":"2008","unstructured":"Li, A., Felix, J. C., Yang, W. & Jain, J. K. Effect of mifepristone on the expression of endometrial secretory leukocyte protease inhibitor in new medroxyprogesterone acetate users. Fertil. Steril. 90, 872\u2013875 (2008).","journal-title":"Fertil. Steril."},{"key":"40756_CR23","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1016\/S0015-0282(02)04930-0","volume":"79","author":"DC Fleming","year":"2003","unstructured":"Fleming, D. C., King, A. E., Williams, A. R., Critchley, H. O. & Kelly, R. W. Hormonal contraception can suppress natural antimicrobial gene transcription in human endometrium. Fertil. Steril. 79, 856\u2013863 (2003).","journal-title":"Fertil. Steril."},{"key":"40756_CR24","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1210\/en.2012-1850","volume":"154","author":"RP Huijbregts","year":"2013","unstructured":"Huijbregts, R. P. et al. Hormonal contraception and HIV-1 infection: medroxyprogesterone acetate suppresses innate and adaptive immune mechanisms. Endocrinology 154, 1282\u20131295 (2013).","journal-title":"Endocrinology"},{"key":"40756_CR25","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1097\/QAI.0000000000000975","volume":"72","author":"K Butler","year":"2016","unstructured":"Butler, K. et al. A Depot Medroxyprogesterone Acetate Dose That Models Human Use and Its Effect on Vaginal SHIV Acquisition Risk. J. Acquir. Immune Defic. Syndr. 72, 363\u2013371 (2016).","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"40756_CR26","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1128\/IAI.01189-12","volume":"81","author":"L Kleynhans","year":"2013","unstructured":"Kleynhans, L. et al. The contraceptive depot medroxyprogesterone acetate impairs mycobacterial control and inhibits cytokine secretion in mice infected with Mycobacterium tuberculosis. Infect. Immun. 81, 1234\u20131244 (2013).","journal-title":"Infect. Immun."},{"key":"40756_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/srep37723","volume":"6","author":"NE Quispe Calla","year":"2016","unstructured":"Quispe Calla, N. E. et al. Dendritic cell function and pathogen-specific T cell immunity are inhibited in mice administered levonorgestrel prior to intranasal Chlamydia trachomatis infection. Sci. Rep. 6, 37723 (2016).","journal-title":"Sci. Rep."},{"key":"40756_CR28","doi-asserted-by":"publisher","first-page":"9845","DOI":"10.1128\/JVI.77.18.9845-9851.2003","volume":"77","author":"AE Gillgrass","year":"2003","unstructured":"Gillgrass, A. E., Ashkar, A. A., Rosenthal, K. L. & Kaushic, C. Prolonged exposure to progesterone prevents induction of protective mucosal responses following intravaginal immunization with attenuated herpes simplex virus type 2. J. Virol. 77, 9845\u20139851 (2003).","journal-title":"J. Virol."},{"key":"40756_CR29","doi-asserted-by":"publisher","first-page":"3449","DOI":"10.4049\/jimmunol.1103054","volume":"189","author":"RD Vicetti Miguel","year":"2012","unstructured":"Vicetti Miguel, R. D. et al. Dendritic cell activation and memory cell development are impaired among mice administered medroxyprogesterone acetate prior to mucosal herpes simplex virus type 1 infection. J. Immunol. 189, 3449\u20133461 (2012).","journal-title":"J. Immunol."},{"key":"40756_CR30","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1097\/QAD.0000000000000681","volume":"29","author":"ME Sampah","year":"2015","unstructured":"Sampah, M. E., Laird, G. M., Blankson, J. N., Siliciano, R. F. & Coleman, J. S. Medroxyprogesterone acetate increases HIV-1 infection of unstimulated peripheral blood mononuclear cells in vitro. AIDS 29, 1137\u20131146 (2015).","journal-title":"AIDS"},{"key":"40756_CR31","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1093\/infdis\/jiu832","volume":"211","author":"VH Ferreira","year":"2015","unstructured":"Ferreira, V. H. et al. Medroxyprogesterone Acetate Regulates HIV-1 Uptake and Transcytosis but Not Replication in Primary Genital Epithelial Cells, Resulting in Enhanced T-Cell Infection. J. Infect. Dis. 211, 1745\u20131756 (2015).","journal-title":"J. Infect. Dis."},{"key":"40756_CR32","doi-asserted-by":"publisher","first-page":"e96497","DOI":"10.1371\/journal.pone.0096497","volume":"9","author":"Y Govender","year":"2014","unstructured":"Govender, Y. et al. The injectable-only contraceptive medroxyprogesterone acetate, unlike norethisterone acetate and progesterone, regulates inflammatory genes in endocervical cells via the glucocorticoid receptor. PLoS One 9, e96497 (2014).","journal-title":"PLoS One"},{"key":"40756_CR33","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1093\/humrep\/dev035","volume":"30","author":"NE Quispe Calla","year":"2015","unstructured":"Quispe Calla, N. E., Ghonime, M. G., Cherpes, T. L. & Vicetti Miguel, R. D. Medroxyprogesterone acetate impairs human dendritic cell activation and function. Hum. Reprod. 30, 1169\u20131177 (2015).","journal-title":"Hum. Reprod."},{"key":"40756_CR34","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/j.steroids.2011.03.001","volume":"76","author":"D Africander","year":"2011","unstructured":"Africander, D., Verhoog, N. & Hapgood, J. P. Molecular mechanisms of steroid receptor-mediated actions by synthetic progestins used in HRT and contraception. Steroids 76, 636\u2013652 (2011).","journal-title":"Steroids"},{"key":"40756_CR35","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1023\/A:1020072325818","volume":"3","author":"FZ Stanczyk","year":"2002","unstructured":"Stanczyk, F. Z. Pharmacokinetics and potency of progestins used for hormone replacement therapy and contraception. Rev. Endocr. Metab. Disord. 3, 211\u2013224 (2002).","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"40756_CR36","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.mce.2008.10.008","volume":"299","author":"K Ronacher","year":"2009","unstructured":"Ronacher, K. et al. Ligand-selective transactivation and transrepression via the glucocorticoid receptor: role of cofactor interaction. Mol. Cell. Endocrinol. 299, 219\u2013231 (2009).","journal-title":"Mol. Cell. Endocrinol."},{"key":"40756_CR37","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.mce.2005.07.001","volume":"242","author":"D Koubovec","year":"2005","unstructured":"Koubovec, D., Ronacher, K., Stubsrud, E., Louw, A. & Hapgood, J. P. Synthetic progestins used in HRT have different glucocorticoid agonist properties. Mol. Cell. Endocrinol. 242, 23\u201332 (2005).","journal-title":"Mol. Cell. Endocrinol."},{"key":"40756_CR38","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1111\/aji.12214","volume":"71","author":"JP Hapgood","year":"2014","unstructured":"Hapgood, J. P., Ray, R. M., Govender, Y., Avenant, C. & Tomasicchio, M. Differential glucocorticoid receptor-mediated effects on immunomodulatory gene expression by progestin contraceptives: implications for HIV-1 pathogenesis. Am. J. Reprod. Immunol. 71, 505\u2013512 (2014).","journal-title":"Am. J. Reprod. Immunol."},{"key":"40756_CR39","doi-asserted-by":"publisher","first-page":"e24639","DOI":"10.1371\/journal.pone.0024639","volume":"6","author":"L Kleynhans","year":"2011","unstructured":"Kleynhans, L. et al. Medroxyprogesterone acetate alters Mycobacterium bovis BCG-induced cytokine production in peripheral blood mononuclear cells of contraceptive users. PLoS One 6, e24639 (2011).","journal-title":"PLoS One"},{"key":"40756_CR40","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.mce.2004.03.006","volume":"221","author":"D Koubovec","year":"2004","unstructured":"Koubovec, D., Vanden Berghe, W., Vermeulen, L., Haegeman, G. & Hapgood, J. P. Medroxyprogesterone acetate downregulates cytokine gene expression in mouse fibroblast cells. Mol. Cell. Endocrinol. 221, 75\u201385 (2004).","journal-title":"Mol. Cell. Endocrinol."},{"key":"40756_CR41","doi-asserted-by":"publisher","first-page":"31136","DOI":"10.1074\/jbc.M114.587311","volume":"289","author":"R Louw-du Toit","year":"2014","unstructured":"Louw-du Toit, R., Hapgood, J. P. & Africander, D. Medroxyprogesterone Acetate Differentially Regulates Interleukin (IL)-12 and IL-10 in a Human Ectocervical Epithelial Cell Line in a Glucocorticoid Receptor (GR)-dependent Manner. J. Biol. Chem. 289, 31136\u201331149 (2014).","journal-title":"J. Biol. Chem."},{"key":"40756_CR42","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1210\/jcem-44-1-32","volume":"44","author":"A Ortiz","year":"1977","unstructured":"Ortiz, A., Hirol, M., Stanczyk, F. Z., Goebelsmann, U. & Mishell, D. R. Serum medroxyprogesterone acetate (MPA) concentrations and ovarian function following intramuscular injection of depo-MPA. J. Clin. Endocrinol. Metab. 44, 32\u201338 (1977).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"40756_CR43","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1530\/acta.0.0990339","volume":"99","author":"S Jeppsson","year":"1982","unstructured":"Jeppsson, S., Gershagen, S., Johansson, E. D. & Rannevik, G. Plasma levels of medroxyprogesterone acetate (MPA), sex-hormone binding globulin, gonadal steroids, gonadotrophins and prolactin in women during long-term use of depo-MPA (Depo-Provera) as a contraceptive agent. Acta Endocrinol. (Copenh.) 99, 339\u2013343 (1982).","journal-title":"Acta Endocrinol. (Copenh.)"},{"key":"40756_CR44","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.contraception.2014.01.017","volume":"89","author":"AE Bonny","year":"2014","unstructured":"Bonny, A. E., Lange, H. L., Rogers, L. K., Gothard, D. M. & Reed, M. D. A pilot study of depot medroxyprogesterone acetate pharmacokinetics and weight gain in adolescent females. Contraception 89, 357\u2013360 (2014).","journal-title":"Contraception"},{"key":"40756_CR45","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/0010-7824(80)90105-5","volume":"22","author":"K Fotherby","year":"1980","unstructured":"Fotherby, K., Koetsawang, S. & Mathrubutham, M. Pharmacokinetic study of different doses of Depo Provera. Contraception 22, 527\u2013536 (1980).","journal-title":"Contraception"},{"key":"40756_CR46","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/S0015-0282(16)44895-8","volume":"34","author":"K Fotherby","year":"1980","unstructured":"Fotherby, K. et al. A preliminary pharmacokinetic and pharmacodynamic evaluation of depot-medroxyprogesterone acetate and norethisterone oenanthate. Fertil. Steril. 34, 131\u2013139 (1980).","journal-title":"Fertil. Steril."},{"key":"40756_CR47","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/0022-4731(78)90631-3","volume":"9","author":"K Shrimanker","year":"1978","unstructured":"Shrimanker, K., Saxena, B. N. & Fotherby, K. A radioimmunoassay for serum medroxyprogesterone acetate. J. Steroid Biochem. 9, 359\u2013363 (1978).","journal-title":"J. Steroid Biochem."},{"key":"40756_CR48","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/S0010-7824(76)80060-1","volume":"14","author":"S Jeppsson","year":"1976","unstructured":"Jeppsson, S. & Johansson, E. D. Medroxyprogesterone acetate, estradiol, FSH and LH in peripheral blood after intramuscular administration of Depo-Provera\u00ae to women. Contraception 14, 461\u2013469 (1976).","journal-title":"Contraception"},{"key":"40756_CR49","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/S0010-7824(96)00170-9","volume":"54","author":"P Virutamasen","year":"1996","unstructured":"Virutamasen, P. et al. Pharmacodynamic effects of depot-medroxyprogesterone acetate (DMPA) administered to lactating women on their male infants. Contraception 54, 153\u2013157 (1996).","journal-title":"Contraception"},{"key":"40756_CR50","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/0010-7824(74)90130-9","volume":"10","author":"KT Kirton","year":"1974","unstructured":"Kirton, K. T. & Cornette, J. C. Return of ovulatory cyclicity following an intramuscular injection of medroxyprogesterone acetate (Provera). Contraception 10, 39\u201345 (1974).","journal-title":"Contraception"},{"key":"40756_CR51","first-page":"157","volume":"15","author":"S Fang","year":"2004","unstructured":"Fang, S., Sun, D., Jiang, H. & Luo, H. Concentration changes of medroxyprogesterone acetate in serum and milk in lactating women who used Depo Geston\u00ae. J. Reprod. Contraception 15, 157\u2013162 (2004).","journal-title":"J. Reprod. Contraception"},{"key":"40756_CR52","first-page":"57","volume":"60","author":"S Koetsawang","year":"1977","unstructured":"Koetsawang, S. Injected long-acting medroxyprogesterone acetate. Effect on human lactation and concentrations in milk. J. Med. Assoc. Thai. 60, 57\u201360 (1977).","journal-title":"J. Med. Assoc. Thai."},{"key":"40756_CR53","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1016\/j.fertnstert.2007.07.1348","volume":"90","author":"K Nanda","year":"2008","unstructured":"Nanda, K. et al. Pharmacokinetic interactions between depot medroxyprogesterone acetate and combination antiretroviral therapy. Fertil. Steril. 90, 965\u2013971 (2008).","journal-title":"Fertil. Steril."},{"key":"40756_CR54","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/0010-7824(82)90171-8","volume":"26","author":"K Fotherby","year":"1982","unstructured":"Fotherby, K. & Koetsawang, S. Metabolism of injectable formulations of contraceptive steroids in obese and thin women. Contraception 26, 51\u201358 (1982).","journal-title":"Contraception"},{"key":"40756_CR55","unstructured":"U.S. Food and Drug Administration. Depo-SubQ Provera 104 (medroxyprogesterone acetate) injectable suspension. New drug application no. 021583. Center for Drug Evaluation and Research clinical pharmacology and biopharmaceutics review. Available at: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2005\/021584s000_depo-subQTOC.cfm."},{"key":"40756_CR56","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.contraception.2016.03.003","volume":"94","author":"K Nanda","year":"2016","unstructured":"Nanda, K. et al. Medroxyprogesterone acetate levels among Kenyan women using depot medroxyprogesterone acetate in the FEM-PrEP trial. Contraception 94, 40\u201347 (2016).","journal-title":"Contraception"},{"key":"40756_CR57","unstructured":"Pharmacia. Depo-Provera\u00ae Contraceptive Injection. (Pharmacia and Upjohn Company, 2002)."},{"key":"40756_CR58","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.contraception.2013.10.010","volume":"89","author":"JD Shelton","year":"2014","unstructured":"Shelton, J. D. & Halpern, V. Subcutaneous DMPA: a better lower dose approach. Contraception 89, 341\u2013343 (2014).","journal-title":"Contraception"},{"key":"40756_CR59","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.contraception.2004.01.011","volume":"70","author":"J Jain","year":"2004","unstructured":"Jain, J. et al. Pharmacokinetics, ovulation suppression and return to ovulation following a lower dose subcutaneous formulation of Depo-Provera. Contraception 70, 11\u201318 (2004).","journal-title":"Contraception"},{"key":"40756_CR60","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1016\/j.clinthera.2004.11.013","volume":"26","author":"YC Toh","year":"2004","unstructured":"Toh, Y. C., Jain, J., Rahnny, M. H., Bode, F. R. & Ross, D. Suppression of ovulation by a new subcutaneous depot medroxyprogesterone acetate (104 mg\/0.65 mL) contraceptive formulation in Asian women. Clin. Ther. 26, 1845\u20131854 (2004).","journal-title":"Clin. Ther."},{"key":"40756_CR61","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.contraception.2013.07.002","volume":"89","author":"V Halpern","year":"2014","unstructured":"Halpern, V., Combes, S. L., Dorflinger, L. J., Weiner, D. H. & Archer, D. F. Pharmacokinetics of subcutaneous depot medroxyprogesterone acetate injected in the upper arm. Contraception 89, 31\u201335 (2014).","journal-title":"Contraception"},{"key":"40756_CR62","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.contraception.2009.02.005","volume":"80","author":"AM Kaunitz","year":"2009","unstructured":"Kaunitz, A. M., Darney, P. D., Ross, D., Wolter, K. D. & Speroff, L. Subcutaneous DMPA vs. intramuscular DMPA: a 2-year randomized study of contraceptive efficacy and bone mineral density. Contraception 80, 7\u201317 (2009).","journal-title":"Contraception"},{"key":"40756_CR63","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/0010-7824(81)90065-2","volume":"24","author":"GW Sang","year":"1981","unstructured":"Sang, G. W., Fotherby, K., Howard, G., Elder, M. & Bye, P. G. Pharmacokinetics of norethisterone oenanthate in humans. Contraception 24, 15\u201327 (1981).","journal-title":"Contraception"},{"key":"40756_CR64","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/0010-7824(79)90022-2","volume":"19","author":"U Goebelsmann","year":"1979","unstructured":"Goebelsmann, U. et al. Serum norethindrone (NET) concentrations following intramuscular NET enanthate injection. Effect upon serum LH, FSH, estradiol and progesterone. Contraception 19, 283\u2013313 (1979).","journal-title":"Contraception"},{"key":"40756_CR65","doi-asserted-by":"publisher","first-page":"e0196043","DOI":"10.1371\/journal.pone.0196043","volume":"13","author":"MF Maritz","year":"2018","unstructured":"Maritz, M. F. et al. Medroxyprogesterone acetate, unlike norethisterone, increases HIV-1 replication in human peripheral blood mononuclear cells and an indicator cell line, via mechanisms involving the glucocorticoid receptor, increased CD4\/CD8 ratios and CCR5 levels. PLoS One 13, e0196043 (2018).","journal-title":"PLoS One"},{"key":"40756_CR66","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1128\/jvi.59.2.284-291.1986","volume":"59","author":"A Adachi","year":"1986","unstructured":"Adachi, A. et al. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J. Virol. 59, 284\u2013291 (1986).","journal-title":"J. Virol."},{"key":"40756_CR67","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.virol.2010.08.028","volume":"408","author":"TG Edmonds","year":"2010","unstructured":"Edmonds, T. G. et al. Replication competent molecular clones of HIV-1 expressing Renilla luciferase facilitate the analysis of antibody inhibition in PBMC. Virology 408, 1\u201313 (2010).","journal-title":"Virology"},{"key":"40756_CR68","doi-asserted-by":"publisher","first-page":"8392","DOI":"10.1073\/pnas.90.18.8392","volume":"90","author":"WS Pear","year":"1993","unstructured":"Pear, W. S., Nolan, G. P., Scott, M. L. & Baltimore, D. Production of high-titer helper-free retroviruses by transient transfection. Proc. Natl. Acad. Sci. USA 90, 8392\u20138396 (1993).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"40756_CR69","first-page":"493","volume":"27","author":"LJ Reed","year":"1938","unstructured":"Reed, L. J. & Muench, H. A simple method of estimating fifty percent endpoints. Am. J. Hyg. 27, 493\u2013497 (1938).","journal-title":"Am. J. Hyg."},{"key":"40756_CR70","doi-asserted-by":"publisher","first-page":"11179","DOI":"10.1128\/JVI.79.17.11179-11186.2005","volume":"79","author":"P Fletcher","year":"2005","unstructured":"Fletcher, P. et al. The nonnucleoside reverse transcriptase inhibitor UC-781 inhibits human immunodeficiency virus type 1 infection of human cervical tissue and dissemination by migratory cells. J. Virol. 79, 11179\u201311186 (2005).","journal-title":"J. Virol."},{"key":"40756_CR71","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1007\/978-1-62703-670-2_19","volume":"1087","author":"A Arakelyan","year":"2014","unstructured":"Arakelyan, A., Fitzgerald, W., Grivel, J. C., Vanpouille, C. & Margolis, L. Histocultures (tissue explants) in human retrovirology. Methods Mol Biol 1087, 233\u2013248 (2014).","journal-title":"Methods Mol Biol"},{"key":"40756_CR72","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/nprot.2008.245","volume":"4","author":"JC Grivel","year":"2009","unstructured":"Grivel, J. C. & Margolis, L. Use of human tissue explants to study human infectious agents. Nat. Protoc. 4, 256\u2013269 (2009).","journal-title":"Nat. Protoc."},{"key":"40756_CR73","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1126\/science.aai9383","volume":"356","author":"NR Klatt","year":"2017","unstructured":"Klatt, N. R. et al. Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women. Science 356, 938\u2013945 (2017).","journal-title":"Science"},{"key":"40756_CR74","doi-asserted-by":"publisher","first-page":"5577","DOI":"10.1128\/JVI.74.12.5577-5586.2000","volume":"74","author":"P Greenhead","year":"2000","unstructured":"Greenhead, P. et al. Parameters of human immunodeficiency virus infection of human cervical tissue and inhibition by vaginal virucides. J. Virol. 74, 5577\u20135586 (2000).","journal-title":"J. Virol."},{"key":"40756_CR75","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1111\/aji.12218","volume":"72","author":"MV Patel","year":"2014","unstructured":"Patel, M. V. et al. Innate immunity in the vagina (Part II): Anti-HIV activity and antiviral content of human vaginal secretions. Am. J. Reprod. Immunol. 72, 22\u201333 (2014).","journal-title":"Am. J. Reprod. Immunol."},{"key":"40756_CR76","doi-asserted-by":"publisher","first-page":"e62895","DOI":"10.1371\/journal.pone.0062895","volume":"8","author":"M Tomasicchio","year":"2013","unstructured":"Tomasicchio, M., Avenant, C., Du Toit, A., Ray, R. M. & Hapgood, J. P. The progestin-only contraceptive medroxyprogesterone acetate, but not norethisterone acetate, enhances HIV-1 Vpr-mediated apoptosis in human CD4+ T cells through the glucocorticoid receptor. PLoS One 8, e62895 (2013).","journal-title":"PLoS One"},{"key":"40756_CR77","doi-asserted-by":"publisher","first-page":"e11","DOI":"10.4081\/idr.2011.2370","volume":"3","author":"SK Eszterhas","year":"2011","unstructured":"Eszterhas, S. K., Ilonzo, N. O., Crozier, J. E., Celaj, S. & Howell, A. L. Nanoparticles containing siRNA to silence CD4 and CCR5 reduce expression of these receptors and inhibit HIV-1 infection in human female reproductive tract tissue explants. Infect Dis Rep 3, e11 (2011).","journal-title":"Infect Dis Rep"},{"key":"40756_CR78","doi-asserted-by":"publisher","first-page":"19297","DOI":"10.1074\/jbc.M110.193672","volume":"286","author":"NJ Verhoog","year":"2011","unstructured":"Verhoog, N. J., Du Toit, A., Avenant, C. & Hapgood, J. P. Glucocorticoid-independent repression of tumor necrosis factor (TNF) alpha-stimulated interleukin (IL)-6 expression by the glucocorticoid receptor: a potential mechanism for protection against an excessive inflammatory response. J. Biol. Chem. 286, 19297\u201319310 (2011).","journal-title":"J. Biol. Chem."},{"key":"40756_CR79","doi-asserted-by":"publisher","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","volume":"29","author":"MW Pfaffl","year":"2001","unstructured":"Pfaffl, M. W. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29, e45 (2001).","journal-title":"Nucleic Acids Res."},{"key":"40756_CR80","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1111\/aji.12198","volume":"71","author":"RT Trifonova","year":"2014","unstructured":"Trifonova, R. T., Lieberman, J. & van Baarle, D. Distribution of immune cells in the human cervix and implications for HIV transmission. Am. J. Reprod. Immunol. 71, 252\u2013264 (2014).","journal-title":"Am. J. Reprod. Immunol."},{"key":"40756_CR81","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.contraception.2014.02.006","volume":"90","author":"RP Huijbregts","year":"2014","unstructured":"Huijbregts, R. P., Michel, K. G. & Hel, Z. Effect of progestins on immunity: medroxyprogesterone but not norethisterone or levonorgestrel suppresses the function of T cells and pDCs. Contraception 90, 123\u2013129 (2014).","journal-title":"Contraception"},{"key":"40756_CR82","doi-asserted-by":"publisher","first-page":"e1006402","DOI":"10.1371\/journal.ppat.1006402","volume":"13","author":"A Introini","year":"2017","unstructured":"Introini, A. et al. Seminal plasma induces inflammation and enhances HIV-1 replication in human cervical tissue explants. PLoS Pathog. 13, e1006402 (2017).","journal-title":"PLoS Pathog."},{"key":"40756_CR83","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/QAD.0b013e328333acfb","volume":"24","author":"DJ Anderson","year":"2010","unstructured":"Anderson, D. J., Pudney, J. & Schust, D. J. Caveats associated with the use of human cervical tissue for HIV and microbicide research. AIDS 24, 1\u20134 (2010).","journal-title":"AIDS"},{"key":"40756_CR84","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1038\/mi.2014.26","volume":"7","author":"M Rodriguez-Garcia","year":"2014","unstructured":"Rodriguez-Garcia, M., Barr, F. D., Crist, S. G., Fahey, J. V. & Wira, C. R. Phenotype and susceptibility to HIV infection of CD4+ Th17 cells in the human female reproductive tract. Mucosal Immunol 7, 1375\u20131385 (2014).","journal-title":"Mucosal Immunol"},{"key":"40756_CR85","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1097\/QAI.0b013e318291f331","volume":"63","author":"CS Dezzutti","year":"2013","unstructured":"Dezzutti, C. S. et al. HIV-1 infection of female genital tract tissue for use in prevention studies. J. Acquir. Immune Defic. Syndr. 63, 548\u2013554 (2013).","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"40756_CR86","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1093\/cid\/civ298","volume":"61","author":"L Masson","year":"2015","unstructured":"Masson, L. et al. Genital inflammation and the risk of HIV acquisition in women. Clin. Infect. Dis. 61, 260\u2013269 (2015).","journal-title":"Clin. Infect. Dis."},{"key":"40756_CR87","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1097\/COH.0000000000000232","volume":"11","author":"JA Passmore","year":"2016","unstructured":"Passmore, J. A., Jaspan, H. B. & Masson, L. Genital inflammation, immune activation and risk of sexual HIV acquisition. Curr. Opin. HIV AIDS. 11, 156\u2013162 (2016).","journal-title":"Opin. HIV AIDS."},{"key":"40756_CR88","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1038\/mi.2016.121","volume":"10","author":"KK Smith-McCune","year":"2017","unstructured":"Smith-McCune, K. K. et al. Effects of depot-medroxyprogesterone acetate on the immune microenvironment of the human cervix and endometrium: implications for HIV susceptibility. Mucosal Immunol 10, 1270\u20131278 (2017).","journal-title":"Mucosal Immunol"},{"key":"40756_CR89","doi-asserted-by":"publisher","first-page":"e0143109","DOI":"10.1371\/journal.pone.0143109","volume":"11","author":"SC Francis","year":"2016","unstructured":"Francis, S. C. et al. Immune Activation in the Female Genital Tract: Expression Profiles of Soluble Proteins in Women at High Risk for HIV Infection. PLoS One 11, e0143109 (2016).","journal-title":"PLoS One"},{"key":"40756_CR90","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/QAI.0000000000000533","volume":"69","author":"BL Guthrie","year":"2015","unstructured":"Guthrie, B. L. et al. Depot Medroxyprogesterone Acetate Use Is Associated With Elevated Innate Immune Effector Molecules in Cervicovaginal Secretions of HIV-1-Uninfected Women. J. Acquir. Immune Defic. Syndr. 69, 1\u201310 (2015).","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"40756_CR91","doi-asserted-by":"publisher","first-page":"e0121135","DOI":"10.1371\/journal.pone.0121135","volume":"10","author":"SC Irvin","year":"2015","unstructured":"Irvin, S. C. & Herold, B. C. Molecular mechanisms linking high dose medroxyprogesterone with HIV-1 risk. PLoS One 10, e0121135 (2015).","journal-title":"PLoS One"},{"key":"40756_CR92","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.contraception.2011.06.006","volume":"84","author":"D Africander","year":"2011","unstructured":"Africander, D., Louw, R., Verhoog, N., Noeth, D. & Hapgood, J. P. Differential regulation of endogenous pro-inflammatory cytokine genes by medroxyprogesterone acetate and norethisterone acetate in cell lines of the female genital tract. Contraception 84, 423\u2013435 (2011).","journal-title":"Contraception"},{"key":"40756_CR93","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1095\/biolreprod.105.043133","volume":"73","author":"J Pudney","year":"2005","unstructured":"Pudney, J., Quayle, A. J. & Anderson, D. J. Immunological microenvironments in the human vagina and cervix: mediators of cellular immunity are concentrated in the cervical transformation zone. Biol. Reprod. 73, 1253\u20131263 (2005).","journal-title":"Biol. Reprod."},{"key":"40756_CR94","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1083\/jcb.200203150","volume":"159","author":"D McDonald","year":"2002","unstructured":"McDonald, D. et al. Visualization of the intracellular behavior of HIV in living cells. J. Cell Biol. 159, 441\u2013452 (2002).","journal-title":"J. Cell Biol."},{"key":"40756_CR95","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.jri.2007.01.006","volume":"73","author":"J Mestecky","year":"2007","unstructured":"Mestecky, J. Humoral immune responses to the human immunodeficiency virus type-1 (HIV-1) in the genital tract compared to other mucosal sites. J. Reprod. Immunol. 73, 86\u201397 (2007).","journal-title":"J. Reprod. Immunol."},{"key":"40756_CR96","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1128\/JVI.02216-12","volume":"87","author":"DF King","year":"2013","unstructured":"King, D. F. et al. Mucosal tissue tropism and dissemination of HIV-1 subtype B acute envelope-expressing chimeric virus. J. Virol. 87, 890\u2013899 (2013).","journal-title":"J. Virol."},{"key":"40756_CR97","first-page":"1341","volume":"151","author":"JB Rottman","year":"1997","unstructured":"Rottman, J. B. et al. Cellular localization of the chemokine receptor CCR5. Correlation to cellular targets of HIV-1 infection. Am. J. Pathol. 151, 1341\u20131351 (1997).","journal-title":"Am. J. Pathol."},{"key":"40756_CR98","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1038\/mi.2010.2","volume":"3","author":"E Saba","year":"2010","unstructured":"Saba, E. et al. HIV-1 sexual transmission: early events of HIV-1 infection of human cervico-vaginal tissue in an optimized ex vivo model. Mucosal Immunol 3, 280\u2013290 (2010).","journal-title":"Mucosal Immunol"},{"key":"40756_CR99","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1089\/aid.2012.0271","volume":"29","author":"N Chandra","year":"2013","unstructured":"Chandra, N. et al. Depot medroxyprogesterone acetate increases immune cell numbers and activation markers in human vaginal mucosal tissues. AIDS Res. Hum. Retroviruses. 29, 592\u2013601 (2013).","journal-title":"AIDS Res. Hum. Retroviruses."},{"key":"40756_CR100","doi-asserted-by":"publisher","first-page":"e97767","DOI":"10.1371\/journal.pone.0097767","volume":"9","author":"D Goode","year":"2014","unstructured":"Goode, D. et al. Sex hormones selectively impact the endocervical mucosal microenvironment: implications for HIV transmission. PLoS One 9, e97767 (2014).","journal-title":"PLoS One"},{"key":"40756_CR101","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1038\/mi.2016.72","volume":"10","author":"M Rodriguez-Garcia","year":"2017","unstructured":"Rodriguez-Garcia, M. et al. Dendritic cells from the human female reproductive tract rapidly capture and respond to HIV. Mucosal Immunol 10, 531\u2013544 (2017).","journal-title":"Mucosal Immunol"},{"key":"40756_CR102","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.antiviral.2017.03.003","volume":"142","author":"E Saba","year":"2017","unstructured":"Saba, E. et al. 5-Hydroxytyrosol inhibits HIV-1 replication in primary cells of the lower and upper female reproductive tract. Antiviral Res. 142, 16\u201320 (2017).","journal-title":"Antiviral Res."},{"key":"40756_CR103","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1038\/mi.2013.2","volume":"6","author":"E Saba","year":"2013","unstructured":"Saba, E. et al. Productive HIV-1 infection of human cervical tissue ex vivo is associated with the secretory phase of the menstrual cycle. Mucosal Immunol 6, 1081\u20131090 (2013).","journal-title":"Mucosal Immunol"},{"key":"40756_CR104","doi-asserted-by":"publisher","first-page":"368","DOI":"10.4049\/jimmunol.1502628","volume":"197","author":"A Swaims-Kohlmeier","year":"2016","unstructured":"Swaims-Kohlmeier, A. et al. Progesterone Levels Associate with a Novel Population of CCR5+ CD38+ CD4 T Cells Resident in the Genital Mucosa with Lymphoid Trafficking Potential. J. Immunol. 197, 368\u2013376 (2016).","journal-title":"J. Immunol."},{"key":"40756_CR105","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1038\/mi.2015.63","volume":"8","author":"G Leoni","year":"2015","unstructured":"Leoni, G., Neumann, P. A., Sumagin, R., Denning, T. L. & Nusrat, A. Wound repair: role of immune-epithelial interactions. Mucosal Immunol 8, 959\u2013968 (2015).","journal-title":"Mucosal Immunol"},{"key":"40756_CR106","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1189\/jlb.4A1116-496R","volume":"101","author":"RA Botting","year":"2017","unstructured":"Botting, R. A. et al. Phenotypic and functional consequences of different isolation protocols on skin mononuclear phagocytes. J. Leukoc. Biol. 101, 1393\u20131403 (2017).","journal-title":"J. Leukoc. Biol."},{"key":"40756_CR107","doi-asserted-by":"publisher","first-page":"e85675","DOI":"10.1371\/journal.pone.0085675","volume":"9","author":"LR McKinnon","year":"2014","unstructured":"McKinnon, L. R. et al. Optimizing viable leukocyte sampling from the female genital tract for clinical trials: an international multi-site study. PLoS One 9, e85675 (2014).","journal-title":"PLoS One"},{"key":"40756_CR108","doi-asserted-by":"publisher","first-page":"e0178193","DOI":"10.1371\/journal.pone.0178193","volume":"12","author":"SS Iyer","year":"2017","unstructured":"Iyer, S. S. et al. Characteristics of HIV target CD4 T cells collected using different sampling methods from the genital tract of HIV seronegative women. PLoS One 12, e0178193 (2017).","journal-title":"PLoS One"},{"key":"40756_CR109","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1111\/j.1365-2567.2004.01990.x","volume":"113","author":"GR Yeaman","year":"2004","unstructured":"Yeaman, G. R. et al. Chemokine receptor expression in the human ectocervix: implications for infection by the human immunodeficiency virus-type I. Immunology 113, 524\u2013533 (2004).","journal-title":"Immunology"},{"key":"40756_CR110","first-page":"571","volume":"102","author":"AK Ildgruben","year":"2003","unstructured":"Ildgruben, A. K., Sjoberg, I. M. & Hammarstrom, M. L. Influence of hormonal contraceptives on the immune cells and thickness of human vaginal epithelium. Obstet. Gynecol. 102, 571\u2013582 (2003).","journal-title":"Obstet. Gynecol."},{"key":"40756_CR111","doi-asserted-by":"publisher","first-page":"223","DOI":"10.4049\/immunohorizons.1700047","volume":"1","author":"C Tasker","year":"2017","unstructured":"Tasker, C., Davidow, A., Roche, N. E. & Chang, T. L. Depot medroxyprogesterone acetate administration alters immune markers for HIV preference and increases susceptibility of peripheral CD4(+) T cells to HIV infection. Immunohorizons 1, 223\u2013235 (2017).","journal-title":"Immunohorizons"},{"key":"40756_CR112","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/mi.2015.28","volume":"9","author":"VR Joag","year":"2016","unstructured":"Joag, V. R. et al. Identification of preferential CD4+ T-cell targets for HIV infection in the cervix. Mucosal Immunol 9, 1\u201312 (2016).","journal-title":"Mucosal Immunol"},{"key":"40756_CR113","doi-asserted-by":"publisher","first-page":"3258","DOI":"10.1128\/JVI.01796-08","volume":"83","author":"R Shen","year":"2009","unstructured":"Shen, R. et al. Macrophages in vaginal but not intestinal mucosa are monocyte-like and permissive to human immunodeficiency virus type 1 infection. J. Virol. 83, 3258\u20133267 (2009).","journal-title":"J. Virol."},{"key":"40756_CR114","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.bjid.2016.10.004","volume":"21","author":"LJ Galvao-Lima","year":"2017","unstructured":"Galvao-Lima, L. J. et al. Classical and alternative macrophages have impaired function during acute and chronic HIV-1 infection. Braz. J. Infect. Dis. 21, 42\u201350 (2017).","journal-title":"Braz. J. Infect. Dis."},{"key":"40756_CR115","first-page":"272","volume":"8","author":"P Chen","year":"2017","unstructured":"Chen, P. et al. Perturbations of Monocyte Subsets and Their Association with T Helper Cell Differentiation in Acute and Chronic HIV-1-Infected Patients. Front. Immunol. 8, 272 (2017).","journal-title":"Front. Immunol."},{"key":"40756_CR116","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.virol.2017.01.018","volume":"504","author":"TO Robinson","year":"2017","unstructured":"Robinson, T. O., Zhang, M., Ochsenbauer, C., Smythies, L. E. & Cron, R. Q. CD4 regulatory T cells augment HIV-1 expression of polarized M1 and M2 monocyte derived macrophages. Virology 504, 79\u201387 (2017).","journal-title":"Virology"},{"key":"40756_CR117","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.jsbmb.2014.05.007","volume":"143","author":"DJ Africander","year":"2014","unstructured":"Africander, D. J., Storbeck, K. H. & Hapgood, J. P. A comparative study of the androgenic properties of progesterone and the progestins, medroxyprogesterone acetate (MPA) and norethisterone acetate (NET-A). J. Steroid Biochem. Mol. Biol. 143, 404\u2013415 (2014).","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"40756_CR118","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1210\/er.2012-1008","volume":"34","author":"FZ Stanczyk","year":"2013","unstructured":"Stanczyk, F. Z., Hapgood, J. P., Winer, S. & Mishell, D. R. Jr. Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effects. Endocr. Rev. 34, 171\u2013208 (2013).","journal-title":"Endocr. Rev."},{"key":"40756_CR119","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1177\/1933719115570906","volume":"22","author":"S Ayehunie","year":"2015","unstructured":"Ayehunie, S. et al. Characterization of a Hormone-Responsive Organotypic Human Vaginal Tissue Model: Morphologic and Immunologic Effects. Reprod. Sci. 22, 980\u2013990 (2015).","journal-title":"Reprod. Sci."},{"key":"40756_CR120","doi-asserted-by":"publisher","first-page":"e1006163","DOI":"10.1371\/journal.ppat.1006163","volume":"13","author":"JA Neidleman","year":"2017","unstructured":"Neidleman, J. A. et al. Mucosal stromal fibroblasts markedly enhance HIV infection of CD4+ T cells. PLoS Pathog. 13, e1006163 (2017).","journal-title":"PLoS Pathog."},{"key":"40756_CR121","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1093\/oxfordjournals.humrep.a019335","volume":"11","author":"DJ Schust","year":"1996","unstructured":"Schust, D. J., Anderson, D. J. & Hill, J. A. Progesterone-induced immunosuppression is not mediated through the progesterone receptor. Hum. Reprod. 11, 980\u2013985 (1996).","journal-title":"Hum. Reprod."},{"key":"40756_CR122","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1210\/me.2002-0010","volume":"17","author":"JN Miner","year":"2003","unstructured":"Miner, J. N. et al. A nonsteroidal glucocorticoid receptor antagonist. Mol. Endocrinol. 17, 117\u2013127 (2003).","journal-title":"Mol. Endocrinol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40756-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40756-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40756-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T07:26:59Z","timestamp":1671262019000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40756-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,13]]},"references-count":122,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["40756"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-40756-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,13]]},"assertion":[{"value":"19 January 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 February 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 March 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"4334"}}