{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T07:19:56Z","timestamp":1775027996806,"version":"3.50.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000866","name":"International AIDS Vaccine Initiative","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The impact of exposure to endemic infections on basal immunity and susceptibility to HIV-1 acquisition remains uncertain. We hypothesized that exposure to infections such as cytomegalovirus (CMV), malaria and sexually transmitted infections (STIs) in high-risk individuals may modulate immunity and subsequently increase susceptibility to HIV-1 acquisition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A case-control study nested in an HIV-1 negative high-risk cohort from Coastal Kenya was used. Cases were defined as volunteers who tested HIV-1 positive during follow-up and had a plasma sample collected 3 \u00b1 2 months prior to the estimated date of HIV-1 infection. Controls were individuals who remained HIV-1 negative during the follow-up and were matched 2:1 to cases by sex, age, risk group and follow-up time. STI screening was performed using microscopic and serologic tests. HIV-1 pre-infection plasma samples were used to determined exposure to CMV and malaria using enzyme-linked immunosorbent assays and to quantify forty-one cytokines and soluble factors using multiplexing assays. Multiplexing data were analyzed using principal component analysis. Associations between cytokines and soluble factors with subsequent HIV-1 acquisition were determined using conditional logistic regression models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>Overall, samples from 47 cases and 94 controls were analyzed. While exposure to malaria (p=0.675) and CMV (p=0.470) were not associated with HIV-1 acquisition, exposure to STIs was (48% [95% CI, 33.3 \u2013 63] vs. 26% [95% CI, 17.3 \u2013 35.9]. Ten analytes were significantly altered in cases compared to controls and were clustered into four principal components: PC1 (VEGF, MIP-1\u03b2, VEGF-C and IL-4), PC2 (MCP-1, IL-2 and IL-12p70), PC3 (VEGF-D) and PC4 (Eotaxin-3). PC1, which is suggestive of a Th2-modulatory pathway, was significantly associated with HIV-1 acquisition after controlling for STIs (adjusted odds ratio, (95% CI), p-value: 1.51 [1.14 \u2013 2.00], p=0.004). Elevation of Th2-associated pathways may dampen responses involved in viral immunity, leading to enhanced susceptibility to HIV-1 acquisition. Immunomodulatory interventions aimed at inhibiting activation of Th2-associated pathways may be an additional strategy to STI control for HIV-1 prevention and may reduce dampening of immune responses to vaccination.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1283559","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T04:58:27Z","timestamp":1704949107000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Exposure to common infections may shape basal immunity and potentially HIV-1 acquisition amongst a high-risk population in Coastal Kenya"],"prefix":"10.3389","volume":"14","author":[{"given":"Lynn","family":"Fwambah","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryl","family":"Andisi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Streatfield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Bromell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Hare","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joakim","family":"Esbj\u00f6rnsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thumbi","family":"Ndung\u2019u","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduard J.","family":"Sanders","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amin\u00a0S.","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eunice","family":"Nduati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,11]]},"reference":[{"key":"B1","article-title":"Global Research in Sub-Saharan Africa","year":"2023"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20130\u201312\u2013816768\u20137.00049\u20131","article-title":"Infections that cause secondary immune deficiency","author":"Bonagura","year":"2020","journal-title":"Stiehm\u2019s Immune Defic"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.9.5468\u20135481.2005","article-title":"Concurrent infection with an intestinal helminth parasite impairs host resistance to enteric","volume":"73","author":"Chen","year":"2005","journal-title":"Society"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2007.03.009","article-title":"Chronic helminth infections induce immunomodulation: Consequences and mechanisms","volume":"212","author":"van Riet","year":"2007","journal-title":"Immunobiology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/428593","article-title":"Immunity against helminths: Interactions with the host and the intercurrent infections","volume":"2010","author":"Moreau","year":"2010","journal-title":"J BioMed Biotechnol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/all.13944","article-title":"Regulation of immunity and allergy by helminth parasites","volume":"75","author":"Maizels","year":"2020","journal-title":"Allergy"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.12\u20130431","article-title":"Coinfection with Plasmodium falciparum and Schistosoma haematobium: Additional evidence of the protective effect of schistosomiasis on malaria in Senegalese children","volume":"90","author":"Lemaitre","year":"2014","journal-title":"Am J Trop Med Hyg"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2013020\u20130330\u20135","article-title":"Will helminth co\u2013infection modulate COVID\u201319 severity in endemic regions","volume":"20","author":"Bradbury","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4395","article-title":"Regulatory T cells impede acute and long\u2013term immunity to blood\u2013stage malaria through CTLA\u20134","volume":"23","author":"Kurup","year":"2017","journal-title":"Nat Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00861\u201306","article-title":"The frequency of BDCA3\u2013positive dendritic cells is increased in the peripheral circulation of Kenyan children with severe malaria","volume":"74","author":"Urban","year":"2006","journal-title":"Infect Immun"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12916\u2013019\u20131292\u2013y","article-title":"Repeated clinical malaria episodes are associated with modification of the immune system in children","volume":"17","author":"Bediako","year":"2019","journal-title":"BMC Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202438","article-title":"Chronic exposure to plasmodium falciparum is associated with phenotypic evidence of B and T cell exhaustion","volume":"190","author":"Illingworth","year":"2013","journal-title":"J Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.11.002","article-title":"PD\u20131 dependent exhaustion of CD8+ T cells drives chronic malaria","volume":"5","author":"Horne\u2013Debets","year":"2013","journal-title":"Cell Rep"},{"key":"B14","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/S2055-6640(20)30456-8","article-title":"Human cytomegalovirus (CMV) in Africa: a neglected but important pathogen","volume":"2","author":"Bates","year":"2016","journal-title":"J Virus Erad ."},{"key":"B15","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1007\/s00430\u2013019\u201300610\u2013z","article-title":"Adverse immunological imprinting by cytomegalovirus sensitizing for allergic airway disease","volume":"208","author":"Reddehase","year":"2019","journal-title":"Med Microbiol Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/sti.2010.043224","article-title":"High prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections among HIV\u20131 negative men who have sex with men in coastal Kenya","volume":"86","author":"Sanders","year":"2010","journal-title":"Sex Transm Infect"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1104423","article-title":"The initial interplay between HIV and mucosal innate immunity","volume":"14","author":"Caputo","year":"2023","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000232","article-title":"Genital inflammation, immune activation and risk of sexual HIV acquisition","volume":"11","author":"Passmore","year":"2016","journal-title":"Curr Opin HIV AIDS"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ298","article-title":"Genital inflammation and the risk of HIV acquisition in women","volume":"61","author":"Masson","year":"2015","journal-title":"Clin Infect Dis"},{"key":"B20","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/nrmicro794","article-title":"The role of sexually transmitted diseases in HIV transmission . Vol. 2, Nature Reviews Microbiology","author":"Galvin","year":"2004","journal-title":"Nat Rev Microbiol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1016\/B978\u2013012373944\u20135.00185\u20131","article-title":"Global burden of infectious diseases","volume":"1","author":"Michaud","year":"2009","journal-title":"Encycl Microbiol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/ije\/dyaa100","article-title":"Cohort profile: IAVI\u2019s HIV epidemiology and early infection cohort studies in Africa to support vaccine discovery","volume":"2020","author":"Price","year":"2020","journal-title":"Int J Epidemiol ."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116100","article-title":"Creating an African HIV clinical research and prevention trials network: HIV prevalence, incidence and transmission","volume":"10","author":"Kamali","year":"2015","journal-title":"PloS One"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000012","article-title":"Disease progression by infecting HIV\u20131 subtype in a seroconverter cohort in sub\u2013Saharan Africa","volume":"27","author":"Amornkul","year":"2013","journal-title":"AIDS"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32835b0f81","article-title":"High HIV\u20131 incidence, correlates of HIV\u20131 acquisition, and high viral loads following seroconversion among MSM","volume":"27","author":"Sanders","year":"2013","journal-title":"AIDS"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2240","DOI":"10.1128\/IAI.01585\u201307","article-title":"Breadth and magnitude of antibody responses to multiple plasmodium falciparum merozoite antigens are associated with protection from clinical malaria","volume":"76","author":"Osier","year":"2008","journal-title":"Infect Immun ."},{"key":"B27","unstructured":"EUROIMMUN Anti\u2013IgG CMV ELISA Kit"},{"key":"B28","unstructured":"V\u2013PLEX Human Biomarker 40\u2013Plex Kit"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab139","article-title":"A Stronger Innate Immune Response During Hyperacute HIV\u20131 Infection is associated with Acute retroviral syndrome","volume":"73","author":"Hassan","year":"2021","journal-title":"Clin Infect Dis"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1186\/s12916\u2013020\u201301529\u20136","article-title":"Association between the cytokine storm, immune cell dynamics, and viral replicative capacity in hyperacute HIV infection","volume":"18","author":"Muema","year":"2020","journal-title":"BMC Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix1063","article-title":"Acute retroviral syndrome is associated with high viral burden, CD4 depletion, and immune activation in systemic and tissue compartments","volume":"66","author":"Crowell","year":"2018","journal-title":"Clin Infect Dis"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0175166","article-title":"High prevalence of curable sexually transmitted infections among pregnant women in a rural county hospital in Kilifi, Kenya","volume":"12","author":"Masha","year":"2017","journal-title":"PloS One"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20132002\u201307\u20132305","article-title":"MIP\u20131\u03b1 and MIP\u20131\u03b2 differentially mediate mucosal and systemic adaptive immunity","volume":"101","author":"Lillard","year":"2003","journal-title":"Blood"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nm1105","article-title":"Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2\u2013mediated sensitization and inflammation in the lung","volume":"10","author":"Lee","year":"2004","journal-title":"Nat Med ."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.4.2059","article-title":"IL\u20134 induces differentiation and expansion of Th2 cytokine\u2013producing eosinophils","volume":"172","author":"Chen","year":"2004","journal-title":"J Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20130432.CCR\u201306\u20132416","article-title":"Vascular endothelial growth factor and its relationship to inflammatory mediators","volume":"13","author":"Angelo","year":"2007","journal-title":"Clin Cancer Res"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1172\/JCI17712","article-title":"Proinflammatory functions of vascular endothelial growth factor in alloimmunity","volume":"112","author":"Reinders","year":"2003","journal-title":"J Clin Invest"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/59.5.339","article-title":"Expression of the \u03b2\u2013chemokines RANTES and MIP\u20131\u03b2 by human brain microvessel endothelial cells in primary culture","volume":"59","author":"Shukaliak","year":"2000","journal-title":"J Neuropathol Exp Neurol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/s1359\u20136101(02)00045\u2013x","article-title":"Macrophage inflammatory protein\u20131","volume":"13","author":"Menten","year":"2002","journal-title":"Cytokine Growth Factor Rev ."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00888","article-title":"Tuning the cytokine responses: an update on interleukin (IL)\u20134 and IL\u201313 receptor complexes","volume":"888","author":"Junttila","year":"2018","journal-title":"Front Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1742\u20134690\u20139\u201382","article-title":"Macrophages and their relevance in Human Immunodeficiency Virus Type I infection","volume":"9","author":"Koppensteiner","year":"2012","journal-title":"Retrovirology. BioMed Cent"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1128\/mr.57.1.183\u2013289.1993","article-title":"HIV and the pathogenesis of AIDS, third edition","author":"Levy","year":"2007","journal-title":"Am Soc Microbiol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e15055","article-title":"The cytokine\/chemokine response in Leishmania\/HIV infection and co\u2013infection","volume":"9","author":"Maksoud","year":"2023","journal-title":"Heliyon"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12977\u2013021\u201300552\u20136","article-title":"Elevated levels of inflammatory plasma biomarkers are associated with risk of HIV infection","volume":"18","author":"McInally","year":"2021","journal-title":"Retrovirology"},{"key":"B45","doi-asserted-by":"publisher","first-page":"107598","DOI":"10.1016\/j.intimp.2021.107598","article-title":"MCP\u20131: Function, regulation, and involvement in disease","author":"Singh","year":"2021","journal-title":"Int Immunopharmacol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202205103","article-title":"Productive HIV\u20131 infection of tissue macrophages by fusion with infected CD4+ T cells","volume":"222","author":"Mascarau","year":"2023","journal-title":"J Cell Biol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0128792","article-title":"Changing malaria prevalence on the Kenyan coast since 1974: climate, drugs and vector control","volume":"10","author":"Snow","year":"2015","journal-title":"PloS One"},{"key":"B48","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1086\/504720","article-title":"Clusters of cytokines determine malaria severity in plasmodium falciparum\u2013infected patients from endemic areas of central India","author":"Prakash","year":"2006","journal-title":"J Infect Dis"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1128\/iai.55.4.877\u2013881.1987","article-title":"Killing of Plasmodium falciparum by eosinophil secretory products","volume":"55","author":"Waters","year":"1987","journal-title":"Infect Immun ."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598\u2013019\u201344125\u20132","article-title":"IL\u20131\u03b1 promotes liver inflammation and necrosis during blood\u2013stage Plasmodium chabaudi malaria","volume":"9","author":"de Menezes","year":"2019","journal-title":"Sci Rep"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1257725","article-title":"IP\u201310 and MIG are sensitive markers of early virological response to HIV\u20131 integrase inhibitors","volume":"14","author":"\u00c1lvarez","year":"2023","journal-title":"Front Immunol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000063422.38690.DC","article-title":"The antiinflammatory endothelial tyrosine kinase Tie2 interacts with a novel nuclear factor\u2013kappaB inhibitor ABIN\u20132","volume":"92","author":"Hughes","year":"2003","journal-title":"Circ Res"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/S0065\u20132776(04)86006\u20131","article-title":"Interleukin\u20132, interleukin\u201315, and their roles in human natural killer cells","volume":"86","author":"Becknell","year":"2005","journal-title":"Adv Immunol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2004.02.004","article-title":"Analyzing T\u2013cell responses to cytomegalovirus by cytokine flow cytometry","volume":"65","author":"Maeker","year":"2004","journal-title":"Hum Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1283559\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T04:58:32Z","timestamp":1704949112000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1283559\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,11]]},"references-count":54,"alternative-id":["10.3389\/fimmu.2023.1283559"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1283559","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,11]]},"article-number":"1283559"}}