{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T01:42:47Z","timestamp":1774316567684,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background.<\/jats:title>\n                  <jats:p>Genital immune activation is suspected to modulate local human immunodeficiency virus (HIV) RNA levels and the risk of sexual HIV transmission.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods.<\/jats:title>\n                  <jats:p>A prospective, observational cohort study of 221 HIV-infected men undergoing male circumcision (MC) was conducted in Rakai, Uganda. Penile lavage samples collected from the coronal sulcus at baseline and 4 weekly visits after MC were assayed for pro-inflammatory cytokines and HIV RNA. The main analysis was limited to 175 men with detectable HIV plasma viral load (VL &amp;gt; 400 copies\/mL; n = 808 visits). The primary exposures of interest were individual and total cytokine detection at the previous postoperative visit. Adjusted prevalence risk ratios (adjPRR) of detectable HIV shedding (VL &amp;gt; 40 copies\/mL) were estimated by Poisson regression models with generalized estimating equations and robust variance estimators and included adjustment for plasma HIV VL.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Findings.<\/jats:title>\n                  <jats:p>Among men with a detectable plasma VL, penile HIV shedding was detected at 136 visits (16.8%). Detectable interleukin (IL)-1\u03b2 (adjPRR = 2.14; 95% confidence interval (CI) = 1.02\u20134.48), IL-6 (adjPRR = 2.24; 95% CI = 1.28\u20133.90), IL-8 (adjPRR = 2.42; 95% CI = 1.15\u20135.08), IL-10 (adjPRR = 2.51; 95% CI = 1.67\u20133.80), and IL-13 (adjPRR = 1.87; 95% CI = 1.15\u20133.03) were associated with penile HIV shedding at the subsequent visit. Men with 2\u20134 (adjPRR = 2.36; 95% CI = 1.08\u20135.14) and 5\u20137 (adjPRR = 3.00; 95% CI = 1.28\u20137.01) detectable cytokines had a greater likelihood of detectable penile HIV shedding at the subsequent visit, compared to men with \u2264 1 detectable cytokine. The total number of detectable cytokines was also associated with a higher penile log10 HIV VL at the subsequent visit among HIV shedders.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Interpretation.<\/jats:title>\n                  <jats:p>Pro-inflammatory cytokine production had a dose-dependent and temporal association with penile HIV shedding, suggesting that genital immune activation may increase the risk of sexual HIV transmission by driving local HIV replication.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciw847","type":"journal-article","created":{"date-parts":[[2016,12,8]],"date-time":"2016-12-08T20:23:42Z","timestamp":1481228622000},"page":"776-784","source":"Crossref","is-referenced-by-count":6,"title":["Penile Immune Activation and Risk of HIV Shedding: A Prospective Cohort Study"],"prefix":"10.1093","volume":"64","author":[{"given":"Eshan U.","family":"Patel","sequence":"first","affiliation":[{"name":"Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases 1 , Baltimore, Maryland ;"},{"name":"Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University 2 , Baltimore, Maryland ;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison R.","family":"Kirkpatrick","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases 1 , Baltimore, Maryland ;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Kate","family":"Grabowski","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University 2 , Baltimore, Maryland ;"},{"name":"Rakai Health Sciences Program 3 , Entebbe , ;","place":["Uganda"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Godfrey","family":"Kigozi","sequence":"additional","affiliation":[{"name":"Rakai Health Sciences Program 3 , Entebbe , ;","place":["Uganda"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald H.","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University 2 , Baltimore, Maryland ;"},{"name":"Rakai Health Sciences Program 3 , Entebbe , ;","place":["Uganda"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica L.","family":"Prodger","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases 1 , Baltimore, Maryland ;"},{"name":"Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University 2 , Baltimore, Maryland ;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew D.","family":"Redd","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases 1 , Baltimore, Maryland ;"},{"name":"Department of Medicine, School of Medicine, Johns Hopkins University 4 , Baltimore, Maryland ;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred","family":"Nalugoda","sequence":"additional","affiliation":[{"name":"Rakai Health Sciences Program 3 , Entebbe , ;","place":["Uganda"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Serwadda","sequence":"additional","affiliation":[{"name":"Rakai Health Sciences Program 3 , Entebbe , ;","place":["Uganda"]},{"name":"Institute of Public Health, Makerere University 5 , Kampala , ;","place":["Uganda"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria J.","family":"Wawer","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University 2 , Baltimore, Maryland ;"},{"name":"Rakai Health Sciences Program 3 , Entebbe , ;","place":["Uganda"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas C.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases 1 , Baltimore, Maryland ;"},{"name":"Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University 2 , Baltimore, Maryland ;"},{"name":"Rakai Health Sciences Program 3 , Entebbe , ;","place":["Uganda"]},{"name":"Department of Medicine, School of Medicine, Johns Hopkins University 4 , Baltimore, Maryland ;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron A. 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