{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T06:10:58Z","timestamp":1779257458039,"version":"3.51.4"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23 AI54162, K23 AI079394, K24 AI071113, P30 AI027757, PO1 AI30731"],"award-info":[{"award-number":["K23 AI54162, K23 AI079394, K24 AI071113, P30 AI027757, PO1 AI30731"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002879","name":"Canadian HIV Trials Network, Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["CANFAR\/CTN Postdoctoral Fellowship"],"award-info":[{"award-number":["CANFAR\/CTN Postdoctoral Fellowship"]}],"id":[{"id":"10.13039\/501100002879","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000245","name":"Michael Smith Health Research BC","doi-asserted-by":"publisher","award":["Trainee Award"],"award-info":[{"award-number":["Trainee Award"]}],"id":[{"id":"10.13039\/501100000245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005895","name":"Fred Hutchinson Cancer Research Center","doi-asserted-by":"publisher","award":["Joel Meyers Infectious Disease Scholarship Grant"],"award-info":[{"award-number":["Joel Meyers Infectious Disease Scholarship Grant"]}],"id":[{"id":"10.13039\/100005895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005895","name":"Fred Hutchinson Cancer Research Center","doi-asserted-by":"publisher","award":["Early Detection Initiative"],"award-info":[{"award-number":["Early Detection Initiative"]}],"id":[{"id":"10.13039\/100005895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000862","name":"Doris Duke Charitable Foundation","doi-asserted-by":"publisher","award":["Clinical Scientist Development Award"],"award-info":[{"award-number":["Clinical Scientist Development Award"]}],"id":[{"id":"10.13039\/100000862","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Co-infection with HIV can result in impaired control of cytomegalovirus (CMV) replication, increasing the likelihood of disease and onward transmission. The objective of this analysis was to measure the impact of HIV on CMV replication in an intensively-sampled cohort in Kampala, Uganda.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>CMV seropositive men and women aged 18\u201365, with or without HIV co-infection, were followed for one month. Daily oral swabs and weekly anogenital swabs and plasma were collected. Quantitative CMV PCR was performed on all samples.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Eighty-five participants were enrolled and provided \u22651 oral swab; 43 (51%) were HIV-seropositive. People living with HIV (PLWH; median CD4 count 439 cells\/mm<jats:sup>3<\/jats:sup>; none on antiretrovirals) had 2\u20134 times greater risk of CMV detection at each anatomical site assessed. At the oral site, 773 of 1272 (61%) of samples from PLWH had CMV detected, compared to 214 of 1349 (16%) among people without HIV. Similarly, the mean CMV quantity was higher among PLWH at all anatomical sites, with the largest difference seen for oral swabs (mean difference 1.63 log\/mL; 95% CI 1.13\u20132.13). Among PLWH, absolute quantity of CD4+ T-cells was not associated with risk of CMV detection. HIV plasma RNA quantity was positively correlated with oral CMV shedding frequency, but not detection at other sites.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Mucosal and systemic CMV replication occurs at higher levels in PLWH than people without HIV, particularly oral shedding, which is a major mode of CMV transmission. Increased CMV replication despite relatively preserved CD4+ T-cell counts suggests that additional interventions are required to improve CMV control in PLWH.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0287516","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T17:26:00Z","timestamp":1691169960000},"page":"e0287516","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Increased frequency and quantity of mucosal and plasma cytomegalovirus replication among Ugandan Adults Living with HIV"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6869-2870","authenticated-orcid":true,"given":"Elisabeth","family":"McClymont","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7704-1677","authenticated-orcid":true,"given":"Jeffrey","family":"Bone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jackson","family":"Orem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred","family":"Okuku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Kalinaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Misty","family":"Saracino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2861-8035","authenticated-orcid":true,"given":"Meei-Li","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacy","family":"Selke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Wald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence","family":"Corey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3609-661X","authenticated-orcid":true,"given":"Corey","family":"Casper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Boucoiran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Johnston","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5743-3606","authenticated-orcid":true,"given":"Soren","family":"Gantt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,8,4]]},"reference":[{"issue":"1","key":"pone.0287516.ref001","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1093\/infdis\/jiw076","article-title":"Prospective Characterization of the Risk Factors for Transmission and Symptoms of Primary Human Herpesvirus Infections Among Ugandan Infants","volume":"214","author":"S Gantt","year":"2016","journal-title":"The Journal of infectious diseases"},{"issue":"4","key":"pone.0287516.ref002","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1002\/rmv.655","article-title":"Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection","volume":"20","author":"MJ Cannon","year":"2010","journal-title":"Reviews in Medical Virology"},{"key":"pone.0287516.ref003","first-page":"2456","article-title":"Fields virology","volume":"xx","author":"DM Knipe","year":"2013","journal-title":"Fields virology"},{"issue":"11","key":"pone.0287516.ref004","first-page":"1069","article-title":"Risk of developing cytomegalovirus retinitis in persons infected with the human immunodeficiency virus","volume":"5","author":"P Pertel","year":"1992","journal-title":"Journal of acquired immune deficiency syndromes"},{"issue":"8","key":"pone.0287516.ref005","doi-asserted-by":"crossref","first-page":"7027","DOI":"10.1128\/JVI.73.8.7027-7030.1999","article-title":"DNA load is an independent predictor of CMV disease and survival in advanced AIDS","volume":"73","author":"SA Spector","year":"1999","journal-title":"J Virol"},{"issue":"2","key":"pone.0287516.ref006","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1172\/JCI1101","article-title":"Plasma cytomegalovirus (CMV) DNA load predicts CMV disease and survival in AIDS patients","volume":"101","author":"SA Spector","year":"1998","journal-title":"J Clin Invest"},{"issue":"9427","key":"pone.0287516.ref007","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1016\/S0140-6736(04)16500-8","article-title":"Importance of cytomegalovirus viraemia in risk of disease progression and death in HIV-infected patients receiving highly active antiretroviral therapy","volume":"363","author":"JR Deayton","year":"2004","journal-title":"The Lancet"},{"issue":"2","key":"pone.0287516.ref008","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1056\/NEJM199907083410203","article-title":"Cytomegalovirus Infection and HIV-1 Disease Progression in Infants Born to HIV-1\u2013Infected Women","volume":"341","author":"A Kovacs","year":"1999","journal-title":"The New England Journal of Medicine"},{"key":"pone.0287516.ref009","article-title":"Effect of Immune-Modulatory Interventions on Asymptomatic Cytomegalovirus Shedding during Suppressive Antiretroviral Therapy","author":"E Hastie","year":"2023","journal-title":"J Infect Dis"},{"issue":"2","key":"pone.0287516.ref010","doi-asserted-by":"crossref","first-page":"e16103","DOI":"10.1371\/journal.pone.0016103","article-title":"Seropositivity to cytomegalovirus, inflammation, all-cause and cardiovascular disease-related mortality in the United States","volume":"6","author":"AM Simanek","year":"2011","journal-title":"PloS one"},{"issue":"7","key":"pone.0287516.ref011","doi-asserted-by":"crossref","first-page":"n\/a","DOI":"10.1161\/JAHA.116.005025","article-title":"Cytomegalovirus Infection and Relative Risk of Cardiovascular Disease (Ischemic Heart Disease, Stroke, and Cardiovascular Death): A Meta\u2010Analysis of Prospective Studies Up to 2016","volume":"6","author":"H Wang","year":"2017","journal-title":"Journal of the American Heart Association"},{"key":"pone.0287516.ref012","doi-asserted-by":"crossref","first-page":"1099356","DOI":"10.3389\/fimmu.2023.1099356","article-title":"CD4(+) T cells expressing CX3CR1, GPR56, with variable CD57 are associated with cardiometabolic diseases in persons with HIV","volume":"14","author":"CN Wanjalla","year":"2023","journal-title":"Front Immunol"},{"issue":"7","key":"pone.0287516.ref013","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.3390\/v13071266","article-title":"Cytomegalovirus as an Uninvited Guest in the Response to Vaccines in People Living with HIV","volume":"13","author":"L Royston","year":"2021","journal-title":"Viruses"},{"issue":"1","key":"pone.0287516.ref014","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1086\/514604","article-title":"Shedding of Cytomegalovirus and Herpesviruses 6, 7, and 8 in Saliva of Human Immunodeficiency Virus Type 1-Infected Patients and Healthy Controls","volume":"27","author":"E Lucht","year":"1998","journal-title":"Clinical Infectious Diseases"},{"issue":"7","key":"pone.0287516.ref015","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1128\/JCM.00256-06","article-title":"High Prevalence of Multiple Human Herpesviruses in Saliva from Human Immunodeficiency Virus-Infected Persons in the Era of Highly Active Antiretroviral Therapy","volume":"44","author":"CS Miller","year":"2006","journal-title":"J Clin Microbiol"},{"issue":"7","key":"pone.0287516.ref016","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1002\/jmv.21214","article-title":"Oral mucosal reactivation rates of herpesviruses among HIV-1 seropositive persons","volume":"80","author":"E Griffin","year":"2008","journal-title":"Journal of Medical Virology"},{"issue":"8","key":"pone.0287516.ref017","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1086\/322630","article-title":"Salivary Cytomegalovirus (CMV) Shedding, Glycoprotein B Genotype Distribution, and CMV Disease in Human Immunodeficiency Virus-Seropositive Patients","volume":"33","author":"N Fidouh-Houhou","year":"2001","journal-title":"Clin Inf Dis"},{"issue":"8","key":"pone.0287516.ref018","doi-asserted-by":"crossref","first-page":"ofaa289","DOI":"10.1093\/ofid\/ofaa289","article-title":"Sex Differences in CMV Replication and HIV Persistence During Suppressive ART","volume":"7","author":"S Gianella","year":"2020","journal-title":"Open forum infectious diseases"},{"issue":"6","key":"pone.0287516.ref019","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1093\/infdis\/jiv135","article-title":"Vaginal Cytomegalovirus Shedding Before and After Initiation of Antiretroviral Therapy in Rakai, Uganda","volume":"212","author":"S Gianella","year":"2015","journal-title":"The Journal of infectious diseases"},{"issue":"1","key":"pone.0287516.ref020","doi-asserted-by":"crossref","first-page":"e4222","DOI":"10.1371\/journal.pone.0004222","article-title":"Impact of HIV Infection and Kaposi Sarcoma on Human Herpesvirus-8 Mucosal Replication and Dissemination in Uganda","volume":"4","author":"C Johnston","year":"2009","journal-title":"PLoS ONE"},{"key":"pone.0287516.ref021","article-title":"Scaling up antiretroviral therapy in resource-limited settings","author":"W. Guidelines","year":"2003","journal-title":"treatment guidelines for a public health approach"},{"issue":"1","key":"pone.0287516.ref022","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1086\/509621","article-title":"Frequent and Asymptomatic Oropharyngeal Shedding of Human Herpesvirus 8 among Immunocompetent Men","volume":"195","author":"C Casper","year":"2007","journal-title":"J Infect Dis"},{"issue":"3","key":"pone.0287516.ref023","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1128\/JCM.42.3.1142-1148.2004","article-title":"Optimization of Quantitative Detection of Cytomegalovirus DNA in Plasma by Real-Time PCR","volume":"42","author":"M Boeckh","year":"2004","journal-title":"J Clin Microbiol"},{"issue":"19","key":"pone.0287516.ref024","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1056\/NEJM200011093431904","article-title":"Mucosal shedding of human herpesvirus 8 in men","volume":"343","author":"J Pauk","year":"2000","journal-title":"N Engl J Med"},{"issue":"5","key":"pone.0287516.ref025","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1128\/JCM.01405-06","article-title":"Optimizing PCR Positivity Criterion for Detection of Herpes Simplex Virus DNA on Skin and Mucosa","volume":"45","author":"AS Magaret","year":"2007","journal-title":"J Clin Microbiol"},{"issue":"6","key":"pone.0287516.ref026","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1177\/0962280211427759","article-title":"Extension of the modified Poisson regression model to prospective studies with correlated binary data","volume":"22","author":"GY Zou","year":"2011","journal-title":"Statistical methods in medical research"},{"key":"pone.0287516.ref027","volume-title":"R: A language and environment for statistical computing.","author":"R Core Team","year":"2018"},{"issue":"5","key":"pone.0287516.ref028","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1097\/01.qai.0000155204.96973.c3","article-title":"Cytomegalovirus viremia, mortality, and end-organ disease among patients with AIDS receiving potent antiretroviral therapies","volume":"38","author":"DA Wohl","year":"2005","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"10","key":"pone.0287516.ref029","doi-asserted-by":"crossref","first-page":"e25571","DOI":"10.1371\/journal.pone.0025571","article-title":"Cytomegalovirus Viremia as a Risk Factor for Mortality Prior to Antiretroviral Therapy among HIV-Infected Gold Miners in South Africa","volume":"6","author":"K Fielding","year":"2011","journal-title":"PLoS ONE"},{"issue":"1","key":"pone.0287516.ref030","doi-asserted-by":"crossref","first-page":"13105","DOI":"10.1038\/s41598-017-12994-0","article-title":"Virus and host-specific differences in oral human herpesvirus shedding kinetics among Ugandan women and children","volume":"7","author":"L Matrajt","year":"2017","journal-title":"Scientific reports"},{"issue":"4","key":"pone.0287516.ref031","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1002\/(SICI)1096-9071(199912)59:4<469::AID-JMV8>3.0.CO;2-L","article-title":"Cervical shedding of cytomegalovirus in human immunodeficiency virus type 1-infected women","volume":"59","author":"SB Mostad","year":"1999","journal-title":"Journal of Medical Virology"},{"issue":"4","key":"pone.0287516.ref032","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1093\/infdis\/171.4.1018","article-title":"Seminal Shedding of Human Immunodeficiency Virus Type 1 and Human Cytomegalovirus: Evidence for Different Immunologic Controls","volume":"171","author":"JN Krieger","year":"1995","journal-title":"The Journal of Infectious Diseases"},{"issue":"4","key":"pone.0287516.ref033","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1136\/sti.2008.034751","article-title":"Use of the designation \"shedder\" in mucosal detection of herpes simplex virus DNA involving repeated sampling","volume":"85","author":"A Magaret","year":"2009","journal-title":"Sex Transm Infect"},{"issue":"3","key":"pone.0287516.ref034","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1086\/314939","article-title":"Asymptomatic Primary Cytomegalovirus Infection: Virologic and Immunologic Features","volume":"180","author":"F Zanghellini","year":"1999","journal-title":"The Journal of infectious diseases"},{"issue":"7","key":"pone.0287516.ref035","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1097\/INF.0000000000001877","article-title":"Nonprimary Maternal Cytomegalovirus Infection After Viral Shedding in Infants","volume":"37","author":"I Boucoiran","year":"2018","journal-title":"The Pediatric Infectious Disease Journal"},{"key":"pone.0287516.ref036","author":"UNAIDS","year":"2022","journal-title":"Global HIV & AIDS statistics\u2014Fact sheet"},{"issue":"6","key":"pone.0287516.ref037","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1002\/jmv.24420","article-title":"Risk of congenital cytomegalovirus infection among HIV-exposed uninfected infants is not decreased by maternal nelfinavir use during pregnancy: Nelfinavir and Congenital CMV Infection","volume":"88","author":"S Gantt","year":"2016","journal-title":"Journal of Medical Virology"},{"issue":"6","key":"pone.0287516.ref038","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1097\/QAD.0000000000003499","article-title":"Predictors of intact HIV DNA levels among children in Kenya","volume":"37","author":"J Neary","year":"2023","journal-title":"Aids"},{"issue":"1","key":"pone.0287516.ref039","doi-asserted-by":"crossref","first-page":"e067640","DOI":"10.1136\/bmjopen-2022-067640","article-title":"Influence of letermovir treatment on gut inflammation in people living with HIV on antiretroviral therapy: protocol of the open-label controlled randomised CIAO study","volume":"13","author":"L Royston","year":"2023","journal-title":"BMJ Open"},{"key":"pone.0287516.ref040","unstructured":"Clinicaltrials.gov. Identifier: NCT05085366\u2014A Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1647 Cytomegalovirus (CMV) Vaccine in Healthy Participants 16 to 40 Years of Age 2023 [Available from: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05085366?term=NCT05085366&rank=1."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0287516","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T17:26:39Z","timestamp":1691169999000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0287516"}},"subtitle":[],"editor":[{"given":"Owen","family":"Ngalamika","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,8,4]]},"references-count":40,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0287516","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,4]]}}}