{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:03:58Z","timestamp":1790960638566,"version":"4.1.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Depot medroxyprogesterone acetate (DMPA) injectable, etonogestrel subdermal implant (ENG-implant), and levonorgestrel intrauterine device (LNG-IUD) are effective, widely used female hormonal contraceptives (HC). Observational studies, but not a randomized trial, suggest increased risk of HIV acquisition with HC use, particularly DMPA. Sexual acquisition of HIV occurs via CD4+ T cells expressing C-C chemokine receptor type 5 (CCR5), though other immunologic cells play a role. This study examined longitudinal changes in CCR5+ T cells and other immunologic cells in the female genital tract following HC initiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      HIV negative participants aged 18\u201345 years, not using HC, were recruited in Atlanta, Georgia. After two pre-HC visits, participants initiated DMPA, ENG-implant, or LNG-IUD and completed visits every three months for one year. Specimens (peripheral blood, endocervical cells, cervical tissue biopsy, and cervicovaginal lavage [CVL]) were analyzed for immune cellular markers (CD45, CD3, CD4, CCR5, CD69, HLA-DR, CD38, \u03b14\u03b27, CD103, Fox-P3, and Ki-67) using flow cytometry. Effects of CVL on HIV infection of cells\n                      <jats:italic>in vitro<\/jats:italic>\n                      was assessed. Vaginal microbiome was characterized via 16S rRNA gene amplicon sequencing. Multivariable linear mixed effects models estimated association between HC and immune markers (Primary outcome: proportion of CD4+ T cells expressing CCR5; Secondary outcomes: other immune markers,\n                      <jats:italic>in vitro<\/jats:italic>\n                      HIV enhancement). A Bonferroni correction was applied.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 118 participants (mean age 25.9; 44.1% self-identified as Black race), 545 visits were completed from 2019-2023. No significant changes were observed in proportion of CCR5+ T cells in any tissue type post-HC. There were statistically significant but moderate absolute decreases in proportion of CD45+ and CD4+ T cells in CVL, and CD4+ T cells in blood, and increased proportion of CD69+ T cells in blood post-HC. Post-HC CVL vs. pre-HC enhanced HIV infection of cells\n                      <jats:italic>in vitro<\/jats:italic>\n                      for all three HC groups (p&amp;lt;0.01) and was modified by the vaginal microbiome. There was also evidence of interaction by time and microbiome parameters for several other immune cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Our findings suggest that commonly used HC methods do not result in immunologic changes that increase HIV acquisition risk. However, HIV infection enhancement with post-HC CVL\n                      <jats:italic>in vitro<\/jats:italic>\n                      warrants further study.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1655678","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T07:06:02Z","timestamp":1764227162000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["No change in key HIV target cell markers following initiation of three progestin-based hormonal contraception methods: findings from the CHIME study"],"prefix":"10.3389","volume":"16","author":[{"given":"Marisa R.","family":"Young","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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