{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:03:54Z","timestamp":1790960634623,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill & Melinda Gates Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000200","name":"US Agency for International Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000200","id-type":"DOI","asserted-by":"crossref"}]},{"name":"President\u2019s Emergency Plan for AIDS Relief"},{"DOI":"10.13039\/100004441","name":"Swedish International Development Cooperation Agency","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004441","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"crossref"}]},{"name":"UN Population Fund"},{"name":"Government of South Africa"},{"DOI":"10.13039\/100000200","name":"US Agency for International Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000200","id-type":"DOI","asserted-by":"crossref"}]},{"name":"US National Institute of Child Health and Human Development"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HD089831-05"],"award-info":[{"award-number":["R01HD089831-05"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"ECHO Biological Mechanisms Ancillary Study"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Cervicovaginal CD4+ T cells are preferential targets for human immunodeficiency virus (HIV) infection and have consequently been used as a proxy measure for HIV susceptibility. The ECHO randomized trial offered a unique opportunity to consider the association between contraceptives and Th17-like cells within a trial designed to evaluate HIV risk. In a mucosal substudy of the ECHO trial, we compared the impact of initiating intramuscular depot medroxyprogesterone acetate (DMPA-IM), copper-IUD, and the levonorgestrel (LNG) implant on cervical T cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Cervical cytobrushes from 58 women enrolled in the ECHO trial were collected at baseline and 1 month after contraceptive initiation. We phenotyped cervical T cells using multiparameter flow cytometry, characterized the vaginal microbiome using 16s sequencing, and determined proteomic signatures associated with Th17-like cells using mass spectrometry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Unlike the LNG implant or copper-IUD, DMPA-IM was associated with higher frequencies of cervical Th17-like cells within 1 month of initiation (P = .012), including a highly susceptible, activated population co-expressing CD38, CCR5, and \u03b14\u03b27 (P = .003). After 1 month, women using DMPA-IM also had more Th17-like cells than women using the Cu-IUD (P = .0002) or LNG implant (P = .04). Importantly, in women using DMPA-IM, proteomic signatures signifying enhanced mucosal barrier function were associated with the increased abundance of Th17-like cells. We also found that a non\u2013Lactobacillus-dominant microbiome at baseline was associated with more Th17-like cells post\u2013DMPA-IM (P = .03), although this did not influence barrier function.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our data suggest that DMPA-IM\u2013driven accumulation of HIV-susceptible Th17-like cells might be counteracted by their role in maintaining mucosal barrier integrity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT02550067.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciac284","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T04:13:15Z","timestamp":1660018395000},"page":"2000-2011","source":"Crossref","is-referenced-by-count":15,"title":["Initiating Intramuscular Depot Medroxyprogesterone Acetate Increases Frequencies of Th17-like Human Immunodeficiency Virus Target Cells in the Genital Tract of Women in South Africa: A Randomized Trial"],"prefix":"10.1093","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8471-163X","authenticated-orcid":false,"given":"Rubina","family":"Bunjun","sequence":"first","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine, Department of Pathology, University of Cape Town , Cape Town , South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanko F","family":"Ramla","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine, Department of Pathology, University of Cape Town , Cape Town , South Africa"},{"name":"The Medical Research Centre, Institute of Medical Research and Medicinal Plant Studies (IMPM), Ministry of Scientific Research and Innovation , Yaound\u00e9 , Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shameem Z","family":"Jaumdally","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine, Department of Pathology, University of Cape Town , Cape Town , South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"No\u00ebl-Romas","sequence":"additional","affiliation":[{"name":"Center for Global Health and Diseases, Case Western Reserve University , Cleveland, Ohio , USA"},{"name":"Department of Obstetrics and Gynecology, University of Manitoba , Winnipeg , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossaena","family":"Ayele","sequence":"additional","affiliation":[{"name":"Center for Global Health and Diseases, Case Western Reserve University , Cleveland, Ohio , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan P","family":"Brown","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute , Seattle, Washington , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoyam","family":"Gamieldien","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine, Department of Pathology, University of Cape Town , Cape Town , South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rushil","family":"Harryparsad","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine, Department of Pathology, University of Cape Town , Cape Town , South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smritee","family":"Dabee","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine, Department of Pathology, University of Cape Town , Cape Town , South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonasagrie","family":"Nair","sequence":"additional","affiliation":[{"name":"Desmond Tutu HIV Foundation (DTHF) , Cape Town , South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maricianah","family":"Onono","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute , Nairobi , Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thesla","family":"Palanee-Phillips","sequence":"additional","affiliation":[{"name":"Wits Reproductive Health and HIV Institute (WHRI) , Johannesburg , South Africa"},{"name":"University of Washington , Seattle, Washington , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catilin W","family":"Scoville","sequence":"additional","affiliation":[{"name":"University of Washington , Seattle, Washington , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate 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