{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:03:56Z","timestamp":1790960636471,"version":"4.1.0"},"reference-count":29,"publisher":"BMJ","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01 HD077888"],"award-info":[{"award-number":["R01 HD077888"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01 HD099091"],"award-info":[{"award-number":["R01 HD099091"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Sex Transm Infect"],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To examine innate immunity predictors of HIV-1 acquisition as biomarkers of HSV-2 risk and biological basis for epidemiologically established HIV-1 predisposition in HSV-2 infected women.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed longitudinal samples from HIV-1 negative visits of 1019\u2009women before and after HSV-2 acquisition. We measured cervical and serum biomarkers of inflammation and immune activation previously linked to HIV-1 risk. Protein levels were Box-Cox transformed and ORs for HSV-2 acquisition were calculated based on top quartile or below\/above median levels for all HSV-2 negative visits. Bivariate analysis determined the likelihood of HSV-2 acquisition by biomarker levels preceding infection. Linear mixed-effects models evaluated if biomarkers differed by HSV-2 status defined as negative, incident or established infections with an established infection cut-off starting at 6 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the cervical compartment, two biomarkers of HIV-1 risk (low SLPI and high BD-2) also predicted HSV-2 acquisition. In addition, HSV-2 acquisition was associated with IL-1\u03b2, IL-6, IL-8, MIP-3\u03b1, ICAM-1 and VEGF when below median levels. Systemic immunity predictors of HSV-2 acquisition were high sCD14 and IL-6, with highest odds when concomitantly increased (OR=2.23, 1.49\u20133.35). Concomitant systemic and mucosal predictors of HSV-2 acquisition risk included (1) serum top quartile sCD14 with cervical low SLPI, VEGF and ICAM-1, or high BD-2; (2) serum high IL-6 with cervical low VEGF and ICAM-1, SLPI, IL-1\u03b2 and IL-6; and (3) serum low C reactive protein with cervical high BD-2 (the only combination also predictive of HIV-1 acquisition). Most cervical biomarkers were decreased after HSV-2 acquisition compared with the HSV-2 negative visits, with incident infections associated with a larger number of suppressed cervical biomarkers and lower serum IL-6 levels compared with established infections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A combination of systemic immunoinflammatory and cervical immunosuppressed states predicts HSV-2 acquisition. A persistently suppressed innate immunity during incident HSV-2 infection may add to the increased HIV-1 susceptibility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/sextrans-2022-055458","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T13:25:20Z","timestamp":1663161920000},"page":"sextrans-2022-055458","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Cervical and systemic innate immunity predictors of HIV risk linked to genital herpes acquisition and time from HSV-2 seroconversion"],"prefix":"10.1136","author":[{"given":"Yashini","family":"Govender","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles 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F","family":"Doncel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9980-5735","authenticated-orcid":false,"given":"Raina Nakova","family":"Fichorova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"2023051210202352000_sextrans-2022-055458v2.1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002511"},{"key":"2023051210202352000_sextrans-2022-055458v2.2","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000198081.09337.a7"},{"key":"2023051210202352000_sextrans-2022-055458v2.3","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3282004929"},{"key":"2023051210202352000_sextrans-2022-055458v2.4","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0b013e32833a8844"},{"key":"2023051210202352000_sextrans-2022-055458v2.5","doi-asserted-by":"publisher","DOI":"10.1258\/ijsa.2012.011356"},{"key":"2023051210202352000_sextrans-2022-055458v2.6","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/942937"},{"key":"2023051210202352000_sextrans-2022-055458v2.7","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1097\/QAI.0000000000002299","article-title":"Concomitant imbalances of systemic and mucosal immunity increase HIV acquisition risk","volume":"84","author":"Morrison","year":"2020","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2023051210202352000_sextrans-2022-055458v2.8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0224359"},{"key":"2023051210202352000_sextrans-2022-055458v2.9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119237"},{"key":"2023051210202352000_sextrans-2022-055458v2.10","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-131-1-199907060-00004"},{"key":"2023051210202352000_sextrans-2022-055458v2.11","doi-asserted-by":"crossref","first-page":"e00221","DOI":"10.1128\/mBio.00221-15","article-title":"The contribution of cervicovaginal infections to the immunomodulatory effects of hormonal 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