{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T03:12:57Z","timestamp":1784257977235,"version":"3.55.0"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T00:00:00Z","timestamp":1554336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001713","name":"European and Developing Countries Clinical Trials Partnership","doi-asserted-by":"publisher","award":["SP\u00b72011\u00b741304\u00b7038"],"award-info":[{"award-number":["SP\u00b72011\u00b741304\u00b7038"]}],"id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001342","name":"South African Department of Science and Technology","doi-asserted-by":"crossref","award":["DST\/CON 0260\/2012"],"award-info":[{"award-number":["DST\/CON 0260\/2012"]}],"id":[{"id":"10.13039\/501100001342","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0213975","type":"journal-article","created":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T17:36:48Z","timestamp":1554399408000},"page":"e0213975","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":54,"title":["Defining characteristics of genital health in South African adolescent girls and young women at high risk for HIV infection"],"prefix":"10.1371","volume":"14","author":[{"given":"Smritee","family":"Dabee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun L.","family":"Barnabas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie S.","family":"Lennard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shameem Z.","family":"Jaumdally","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoyam","family":"Gamieldien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Balle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Ursula","family":"Happel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon D.","family":"Murugan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Lise","family":"Williamson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nonhlanhla","family":"Mkhize","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janan","family":"Dietrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Chiodi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Hope","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Shattock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenda","family":"Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda-Gail","family":"Bekker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather B.","family":"Jaspan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo-Ann S.","family":"Passmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2019,4,4]]},"reference":[{"key":"ref1","unstructured":"WHO. HIV\/AIDS Fact Sheet. In: Fact sheet No360 [Internet]. World Health Organization; 2015 [cited 25 Feb 2016]. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.who.int\/mediacentre\/factsheets\/fs360\/en\/#\" xlink:type=\"simple\">http:\/\/www.who.int\/mediacentre\/factsheets\/fs360\/en\/#<\/ext-link>"},{"key":"ref2","unstructured":"UNAIDS. Empower young women and adolescents girls: Fast tracking the end of the AIDS epidemic in Africa. 2015."},{"key":"ref3","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1093\/cid\/civ298","article-title":"Genital inflammation and the risk of HIV acquisition in women","volume":"61","author":"L Masson","year":"2015","journal-title":"Clin Infect Dis"},{"key":"ref4","first-page":"1","article-title":"Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells","volume":"9","author":"KB Arnold","year":"2015","journal-title":"Mucosal Immunol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.immuni.2015.04.019","article-title":"Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract","volume":"42","author":"MN Anahtar","year":"2015","journal-title":"Immunity"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1097\/QAD.0b013e32833c323b","article-title":"Increased levels of immune activation in the genital tract of healthy young women from sub-Saharan Africa","volume":"24","author":"CR Cohen","year":"2010","journal-title":"Aids"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"4680","DOI":"10.1073\/pnas.1002611107","article-title":"Vaginal microbiome of reproductive-age women","volume":"108","author":"J Ravel","year":"2011","journal-title":"Proc Natl Acad Sci"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1099\/mic.0.081034-0","article-title":"Differences in vaginal microbiome in African American women versus women of European ancestry","volume":"160","author":"JM Fettweis","year":"2014","journal-title":"Microbiology"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1038\/ismej.2014.26","article-title":"Lactobacillus-dominated cervicovaginal microbiota associated with reduced HIV\/STI prevalence and genital HIV viral load in African women","volume":"8","author":"H Borgdorff","year":"2014","journal-title":"ISME J"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1097\/01.gco.0000242952.87125.69","article-title":"Pelvic inflammatory disease in adolescents","volume":"18","author":"RM Gray-Swain","year":"2006","journal-title":"Curr Opin Obstet Gynecol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1783\/147118906776276440","article-title":"Relationship of cervical ectopy to chlamydia infection in young women","volume":"32","author":"V Lee","year":"2006","journal-title":"J Fam Plan Reprod Heal Care"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jri.2010.07.008","article-title":"Higher levels of cervicovaginal inflammatory and regulatory cytokines and chemokines in healthy young women with immature cervical epithelium","volume":"88","author":"LY Hwang","year":"2011","journal-title":"J Reprod Immunol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1086\/427190","article-title":"Influence of sex hormones, HIV status and, concomitant sexually transmitted infection on cervicovaginal inflammation","volume":"191","author":"KG Ghanem","year":"2005","journal-title":"J Infect Dis"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jadohealth.2010.10.009","article-title":"Sexual health, HIV risk, and retention in an adolescent HIV-prevention trial preparatory cohort","volume":"49","author":"HB Jaspan","year":"2011","journal-title":"J Adolesc Heal"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"19408","DOI":"10.7448\/IAS.18.2.19408","article-title":"Adolescent girls and young women: key populations for HIV epidemic control","volume":"18","author":"RCRC Dellar","year":"2015","journal-title":"J Int AIDS Soc"},{"key":"ref16","first-page":"14","article-title":"Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations","volume":"74","author":"R Amsel","year":"1983","journal-title":"Am J Med"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1128\/JCM.29.2.297-301.1991","article-title":"Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation","volume":"29","author":"RP Nugent","year":"1991","journal-title":"J Clin Microbiol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1136\/sextrans-2015-052072","article-title":"Inflammatory cytokine biomarkers to identify women with asymptomatic sexually transmitted infections and bacterial vaginosis who are at high risk of HIV infection","volume":"92","author":"L Masson","year":"2016","journal-title":"Sex Transm Infect"},{"key":"ref19","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00410-17","article-title":"Microbial composition predicts genital tract inflammation and persistent bacterial vaginosis in South African adolescent females","volume":"86","author":"K Lennard","year":"2018","journal-title":"Infect Immun"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1126\/science.aai9383","article-title":"Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women","volume":"356","author":"NR Klatt","year":"2017","journal-title":"Science (80-)"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1177\/0956462417740487","article-title":"Converging epidemics of sexually transmitted infections and bacterial vaginosis in southern African female adolescents at risk of HIV","volume":"29","author":"SL Barnabas","year":"2018","journal-title":"Int J STD AIDS"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1097\/OLQ.0b013e318269cf90","article-title":"Prevalence and Associations of Genital Ulcer and Urethral Pathogens in Men Presenting With Genital Ulcer Syndrome to Primary Health Care Clinics in South Africa","volume":"39","author":"DA Lewis","year":"2012","journal-title":"Sex Transm Dis"},{"key":"ref23","article-title":"CCR5 expression, haplotype and immune activation in protection from infection in HIV-exposed uninfected individuals in HIV serodiscordant relationships","author":"SZ Jaumdally","year":"2017","journal-title":"Immunology"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1093\/infdis\/jir591","article-title":"Immune activation in the female genital tract during HIV infection predicts mucosal CD4 depletion and HIV shedding","volume":"204","author":"HB Jaspan","year":"2011","journal-title":"J Infect Dis"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jim.2011.01.013","article-title":"Stability and transport of cervical cytobrushes for isolation of mononuclear cells from the female genital tract","volume":"367","author":"LJ Liebenberg","year":"2011","journal-title":"J Immunol Methods"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.cacc.2006.03.005","article-title":"Multiple comparisons","volume":"17","author":"MO Columb","year":"2006","journal-title":"Curr Anaesth Crit Care"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"e61217","DOI":"10.1371\/journal.pone.0061217","article-title":"phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data","volume":"8","author":"PJ McMurdie","year":"2013","journal-title":"PLoS One"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1038\/nmeth.2658","article-title":"Differential abundance analysis for microbial marker-gene surveys","volume":"10","author":"JN Paulson","year":"2013","journal-title":"Nat Methods"},{"key":"ref29","article-title":"Generating heatmaps for Nonnegative Matrix Factorization","author":"R Gaujoux","year":"2014"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/S1471-4906(01)02039-7","article-title":"The mucosal immune system: Primary target for HIV infection and AIDS","volume":"22","author":"RS Veazey","year":"2001","journal-title":"Trends Immunol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1097\/QAI.0000000000001218","article-title":"Genital\u2014Systemic Chemokine Gradients and the Risk of HIV Acquisition in Women","volume":"74","author":"LJP Liebenberg","year":"2017","journal-title":"J Acquir Immune Defic Syndr"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1089\/aid.2016.0206","article-title":"Understanding the Intersection of Young Age, Mucosal Injury, and HIV Susceptibility","volume":"32","author":"KA Porter","year":"2016","journal-title":"AIDS Res Hum Retroviruses"},{"issue":"Suppl 1","key":"ref33","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/aji.12043","article-title":"Is early sexual debut a risk factor for HIV infection among women in sub-Saharan Africa? A systematic review","volume":"69","author":"H St\u00f6ckl","year":"2013","journal-title":"Am J Reprod Immunol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S1473-3099(11)70247-X","article-title":"Use of hormonal contraceptives and risk of HIV-1 transmission: A prospective cohort study","volume":"12","author":"R Heffron","year":"2012","journal-title":"Lancet Infect Dis"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"e1001778","DOI":"10.1371\/journal.pmed.1001778","article-title":"Hormonal contraception and the risk of HIV acquisition: An individual participant data meta-analysis","volume":"12","author":"CS Morrison","year":"2015","journal-title":"PLoS Med"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1067\/mpd.2002.128893","article-title":"The interval between menarche and age of first sexual intercourse as a risk factor for subsequent HPV infection in adolescent and young adult women","volume":"141","author":"JA Kahn","year":"2002","journal-title":"J Pediatr"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0178884","article-title":"Early menarche: A systematic review of its effect on sexual and reproductive health in low- and middle-income countries","volume":"12","author":"M Ibitoye","year":"2017","journal-title":"PLoS One"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.maturitas.2003.09.014","article-title":"Classification and pharmacology of progestins","volume":"46","author":"AE Schindler","year":"2003","journal-title":"Maturitas"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/S0002-9378(99)70120-1","article-title":"The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices","volume":"181","author":"R Rivera","year":"1999","journal-title":"Am J Obstet Gynecol"},{"key":"ref40","first-page":"431","article-title":"Depomedroxyprogesterone-induced hypoestrogenism and changes in vaginal flora and epithelium","volume":"96","author":"L Miller","year":"2000","journal-title":"Obstet Gynecol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1111\/j.1471-0528.1998.tb09940.x","article-title":"A double-blind randomised placebo controlled trial of postnatal norethisterone enanthate: The effect on postnatal depression and serum hormones","volume":"105","author":"TA Lawrie","year":"1998","journal-title":"Br J Obstet Gynaecol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/QAI.0000000000000805","article-title":"Mechanisms of HIV transmission in Depo-Provera users: The likely role of hypoestrogenism","volume":"71","author":"M Hickey","year":"2016","journal-title":"J Acquir Immune Defic Syndr"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1089\/aid.2008.0004","article-title":"Positive association between HIV RNA and IL-6 in the genital tract of Rwandan women","volume":"24","author":"GT Spear","year":"2008","journal-title":"AIDS Res Hum Retroviruses"},{"key":"ref44","first-page":"687","article-title":"TRAIL induces apoptosis and activation of NFkB","volume":"9","author":"I Jeremias","year":"1999","journal-title":"Eur Cytokine Netw"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1210\/er.2007-0001","article-title":"The complex role of estrogens in inflammation","volume":"28","author":"RH Straub","year":"2007","journal-title":"Endocr Rev"},{"key":"ref46","article-title":"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","author":"EH Byrne","year":"2015","journal-title":"Lancet Infect Dis"},{"key":"ref47","first-page":"762","article-title":"Vaginal microbiota and its role in HIV transmission and infection","volume":"37","author":"MI Petrova","year":"2013","journal-title":"Fed Eur Microbiol Soc"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jpag.2008.01.073","article-title":"Bacterial populations in the vaginas of healthy adolescent women","volume":"22","author":"T Yamamoto","year":"2009","journal-title":"J Pediatr Adolesc Gynecol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.immuni.2016.12.013","article-title":"Lactobacillus-deficient cervicovaginal bacterial communities are associated with Increased HIV acquisition in young South African women","volume":"46","author":"C Gosmann","year":"2017","journal-title":"Immunity"},{"key":"ref50","first-page":"1","article-title":"The role of lactic acid production by probiotic Lactobacillus species in vaginal health","author":"G Tachedjian","year":"2017","journal-title":"Res Microbiol"},{"key":"ref51","first-page":"1","article-title":"Vaginal lactic acid elicits an anti-inflammatory response from human cervicovaginal epithelial cells and inhibits production of pro-inflammatory mediators associated with HIV acquisition","author":"AC Hearps","year":"2017","journal-title":"Mucosal Immunol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1097\/OLQ.0000000000000298","article-title":"Hydrogen peroxide\u2013producing lactobacilli are associated with lower levels of vaginal interleukin-1\u03b2, independent of bacterial vaginosis","volume":"42","author":"C Mitchell","year":"2015","journal-title":"Sex Transm Dis"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1093\/infdis\/jiu004","article-title":"Bacteria in the vaginal microbiome alter the innate immune response and barrier properties of the human vaginal epithelia in a species-specific manner","volume":"209","author":"SY Doerflinger","year":"2014","journal-title":"J Infect Dis"},{"key":"ref54","first-page":"1","article-title":"Enhanced trapping of HIV-1 by human cervicovaginal mucus Is associated with Lactobacillus crispatus-dominant microbiota","volume":"6","author":"KL Nunn","year":"2015","journal-title":"MBio"},{"key":"ref55","article-title":"Age matters: HIV target cells in the cervix","author":"SL Achilles","year":"2016","journal-title":"Society of Mucosal Immunology"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S1286-4579(02)00056-4","article-title":"Target cells in vaginal HIV transmission","volume":"5","author":"CJ Miller","year":"2003","journal-title":"Microbes Infect"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1172\/JCI1422","article-title":"The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions","volume":"101","author":"S Qin","year":"1998","journal-title":"J Clin Invest"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/mi.2010.58","article-title":"CXCR3 and CCR5 are both required for T cell-mediated protection against C. trachomatis infection in the murine genital mucosa","volume":"4","author":"AJ Olive","year":"2011","journal-title":"Mucosal Immunol"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.virol.2016.03.022","article-title":"Female genital tract inflammation, HIV co-infection and persistent mucosal Human Papillomavirus (HPV) infections","volume":"493","author":"J-M Kriek","year":"2016","journal-title":"Virology"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0213975","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T07:55:23Z","timestamp":1663228523000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0213975"}},"subtitle":[],"editor":[{"given":"Kevin K.","family":"Ari\u00ebn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2019,4,4]]},"references-count":59,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,4,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0213975","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,4]]}}}