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In a cohort of HIV<\/jats:styled-content>\u2010serodiscordant heterosexual couples, we investigated interactions between systemic inflammation and T\u2010cell activation in resistance to HIV<\/jats:styled-content> infection. Males and females in stable long\u2010term relationships with either HIV<\/jats:styled-content>\u2010infected or uninfected partners were recruited, blood T\u2010cell activation (CD<\/jats:styled-content>38, HLA<\/jats:styled-content>\u2010DR<\/jats:styled-content>, CCR<\/jats:styled-content>5 and Ki67) and plasma cytokine concentrations were evaluated. The HIV<\/jats:styled-content>\u2010negative exposed individuals had significantly lower frequencies of CCR<\/jats:styled-content>5+<\/jats:sup> CD<\/jats:styled-content>4+<\/jats:sup> and CD<\/jats:styled-content>8+<\/jats:sup> T cells than unexposed individuals. Mean fluorescence intensity of CCR<\/jats:styled-content>5 expression on CD<\/jats:styled-content>4+<\/jats:sup> T cells was significantly lower in HIV<\/jats:styled-content>\u2010negative exposed than unexposed individuals. Protective CCR<\/jats:styled-content>5 haplotypes (HHA<\/jats:styled-content>\/HHF<\/jats:styled-content>*2, HHF<\/jats:styled-content>*2\/HHF<\/jats:styled-content>*2, HHC<\/jats:styled-content>\/HHF<\/jats:styled-content>*2, HHA<\/jats:styled-content>\/HHA<\/jats:styled-content>, HHA<\/jats:styled-content>\/HHC<\/jats:styled-content> and HHA<\/jats:styled-content>\/HHD<\/jats:styled-content>) tended to be over\u2010represented in exposed compared with unexposed individuals (38% versus 28%, P<\/jats:italic> = 0\u00b758) whereas deleterious genotypes (HHC<\/jats:styled-content>\/HHD<\/jats:styled-content>, HHC<\/jats:styled-content>\/HHE<\/jats:styled-content>, HHD<\/jats:styled-content>\/HHE<\/jats:styled-content>, HHD<\/jats:styled-content>\/HHD<\/jats:styled-content> and HHE<\/jats:styled-content>\/HHE<\/jats:styled-content>) were under\u2010represented (26% versus 44%; P<\/jats:italic> = 0\u00b716). Plasma concentrations of interleukin\u20102 (P<\/jats:italic> = 0\u00b702), interferon\u2010\u03b3<\/jats:italic> (P<\/jats:italic> = 0\u00b705) and granulocyte\u2013macrophage colony\u2010stimulating factor (P<\/jats:italic> = 0\u00b7006) were lower in exposed compared with unexposed individuals. Activation marker expression and systemic cytokine concentrations were not influenced by gender. We conclude that the dominant signature of resistance to HIV<\/jats:styled-content> infection in this cohort of exposed but uninfected individuals was lower T\u2010cell CCR<\/jats:styled-content>5 expression and plasma cytokine concentrations.<\/jats:p>","DOI":"10.1111\/imm.12743","type":"journal-article","created":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T12:32:36Z","timestamp":1491913956000},"page":"464-473","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["CCR<\/scp>5 expression, haplotype and immune activation in protection from infection in HIV<\/scp>\u2010exposed uninfected individuals in HIV<\/scp>\u2010serodiscordant relationships"],"prefix":"10.1111","volume":"151","author":[{"given":"Shameem Z.","family":"Jaumdally","sequence":"first","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine Faculty of Health Sciences University of Cape Town Cape Town South 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STIs National Institute for Communicable Diseases National Health Laboratory Service Johannesburg South Africa"},{"name":"Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather B.","family":"Jaspan","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine Faculty of Health Sciences University of Cape Town Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoyam","family":"Gamieldien","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine Faculty of Health Sciences University of Cape Town Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindi","family":"Masson","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine Faculty of Health Sciences University of Cape Town Cape 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