{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T23:07:58Z","timestamp":1785452878333,"version":"3.56.0"},"reference-count":56,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T00:00:00Z","timestamp":1383264000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["AIDS Research and Human Retroviruses"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:p>\n                    Several microbicides, including nonoxynol-9 (N-9) and cellulose sulfate (CS), looked promising during early trials but failed in efficacy trials. We aimed to identify Phase I mucosal safety endpoints that might explain that failure. In a blinded, randomized, parallel trial, 60 healthy premenopausal sexually abstinent women applied Universal HEC placebo, 6% CS or 4% N-9 gel twice daily for 13\u00bd days. Endpoints included immune biomarkers in cervicovaginal lavage (CVL) and endocervical cytobrushes, inflammatory infiltrates in vaginal biopsies, epithelial integrity by naked eye, colposcopy, and histology, CVL anti-HIV activity, vaginal microflora, pH, and adverse events. Twenty women enrolled per group. Soluble\/cellular markers were similar with CS and placebo, except secretory leukocyte protease inhibitor (SLPI) levels decreased in CVL, and CD3\n                    <jats:sup>+<\/jats:sup>\n                    and CD45\n                    <jats:sup>+<\/jats:sup>\n                    cells increased in biopsies after CS use. Increases in interleukin (IL)-8, IL-1, IL-1RA, and myeloperoxidase (MPO) and decreases in SLPI were significant with N-9. CVL anti-HIV activity was significantly higher during CS use compared to N-9 or placebo. CS users tended to have a higher prevalence of intermediate Nugent score,\n                    <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">Enterococcus<\/jats:italic>\n                    and fewer gram-negative rods. Most Nugent scores diagnostic for bacterial vaginosis were in N-9 users. All cases of histological inflammation or deep epithelial disruption occurred in N-9 users. While the surfactant N-9 showed obvious biochemical and histological signs of inflammation, more subtle changes, including depression of SLPI, tissue influx of CD45\n                    <jats:sup>+<\/jats:sup>\n                    and CD3\n                    <jats:sup>+<\/jats:sup>\n                    cells, and subclinical microflora shifts were associated with CS use and may help to explain the clinical failure of nonsurfactant microbicides.\n                  <\/jats:p>","DOI":"10.1089\/aid.2012.0345","type":"journal-article","created":{"date-parts":[[2013,7,26]],"date-time":"2013-07-26T07:24:47Z","timestamp":1374823487000},"page":"1475-1486","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":15,"title":["Toward Early Safety Alert Endpoints: Exploring Biomarkers Suggestive of Microbicide Failure"],"prefix":"10.1177","volume":"29","author":[{"given":"Christine K.","family":"Mauck","sequence":"first","affiliation":[{"name":"CONRAD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaim Jou","family":"Lai","sequence":"additional","affiliation":[{"name":"Research Triangle Park"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra H.","family":"Weiner","sequence":"additional","affiliation":[{"name":"Research Triangle Park"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neelima","family":"Chandra","sequence":"additional","affiliation":[{"name":"Eastern Virginia Medical School (EVMS)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raina N.","family":"Fichorova","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital and Harvard Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlene S.","family":"Dezzutti","sequence":"additional","affiliation":[{"name":"University of Pittsburgh and Magee-Womens Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon L.","family":"Hillier","sequence":"additional","affiliation":[{"name":"University of Pittsburgh and Magee-Womens Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Archer","sequence":"additional","affiliation":[{"name":"Eastern Virginia Medical School (EVMS)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell D.","family":"Creinin","sequence":"additional","affiliation":[{"name":"University of California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill L.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"CONRAD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne M.","family":"Callahan","sequence":"additional","affiliation":[{"name":"CONRAD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo F.","family":"Doncel","sequence":"additional","affiliation":[{"name":"CONRAD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2013,11,1]]},"reference":[{"issue":"3","key":"e_1_3_2_2_2","first-page":"S174","article-title":"Preclinical assessment of the proinflammatory potential of microbicide candidates","author":"Doncel GF","year":"2004","unstructured":"Doncel GF, , Chandra N, , Fichorova RN. Preclinical assessment of the proinflammatory potential of microbicide candidates. J Acquir Immune Defic Syndr, 2004; Suppl 3:S174\u2013180.","journal-title":"J Acquir Immune Defic Syndr"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)62299-4"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199808203390803"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007435-199803000-00008"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007435-199803000-00007"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.qai.0000159671.25950.74"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)11079-8"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61842-5"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32834541d9"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61086-0"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0010-7824(01)00271-2"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2006.02.008"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000194797.59046.8f"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000226950.72223.5f"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2007.07.004"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2007.05.083"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0010-7824(01)00270-0"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.olq.0000253340.76118.89"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e3181644598"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0707957"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003784"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193748"},{"key":"e_1_3_2_24_2","volume-title":"Conference on Retroviruses and Opportunistic Infections","author":"Marrazzo JM","year":"2013","unstructured":"Marrazzo JM, , Ramjee G, , Nair G et al. Pre-exposure prophylaxis for HIV in women: Daily oral tenofovir, oral tenofovir\/emtricitabine, or vaginal tenofovir gel in the VOICE study (MTN-003) 2013 Conference on Retroviruses and Opportunistic Infections, 2013 Atlanta, GA."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2006.09.003"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025974"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gam028"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.29.2.297-301.1991"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006250-200210000-00025"},{"key":"e_1_3_2_30_2","first-page":"397","article-title":"Evaluation of a rapid enzyme immunoassay test for detection of Group B Streptococcus","volume":"78","author":"Gentry YV","year":"1991","unstructured":"Gentry YV, , Hillier SL, , Eschenbach DA. Evaluation of a rapid enzyme immunoassay test for detection of Group B Streptococcus. Obstet Gynecol, 1991; 78:397\u2013401.","journal-title":"Obstet Gynecol"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00984-06"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.6.1896-1905.2002"},{"key":"e_1_3_2_33_2","first-page":"493","article-title":"A simple method of estimating fifty per cent endpoints","volume":"27","author":"Reed LJ","year":"1938","unstructured":"Reed LJ, , Muench H. A simple method of estimating fifty per cent endpoints. Am J Hygiene, 1938; 27:493\u2013497.","journal-title":"Am J Hygiene"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2011.03.016"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e318186eae7"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1086\/322047"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2011.02.010"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328013d9b5"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2008.00670.x"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e31815d2f12"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016475"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e31823f2aeb"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01152-08"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023136"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1086\/498533"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.9.3607-3615.2005"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011366"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00370-12"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00168-11"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1086\/517820"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1086\/314881"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1086\/315267"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1097\/OLQ.0b013e3181a4f695"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1097\/00042560-199804010-00006"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-6-150"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1159\/000322355"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/381661a0"}],"container-title":["AIDS Research and Human Retroviruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/aid.2012.0345","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/aid.2012.0345","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/aid.2012.0345","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T11:13:13Z","timestamp":1779102793000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/aid.2012.0345"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11]]},"references-count":56,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2013,11]]}},"alternative-id":["10.1089\/aid.2012.0345"],"URL":"https:\/\/doi.org\/10.1089\/aid.2012.0345","relation":{},"ISSN":["0889-2229","1931-8405"],"issn-type":[{"value":"0889-2229","type":"print"},{"value":"1931-8405","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11]]}}}