title: Killer-cell Immunoglobulin-like Receptor (KIR) gene profiles modify HIV disease course, not HIV acquisition in South African women.
abstract: BACKGROUND
  Killer-cell Immunoglobulin-like Receptors (KIR) interact with Human Leukocyte Antigen (HLA) to modify natural killer- and T-cell function. KIR are implicated in HIV acquisition by small studies that have not been widely replicated. A role for KIR in HIV disease progression is more widely replicated and supported by functional studies.
  
  
  METHODS
  To assess the role of KIR and KIR ligands in HIV acquisition and disease course, we studied at-risk women in South Africa between 2004-2010. Logistic regression was used for nested case-control analysis of 154 women who acquired vs. 155 who did not acquire HIV, despite high exposure. Linear mixed-effects models were used for cohort analysis of 139 women followed prospectively for a median of 54 months (IQR 31-69) until 2014.
  
  
  RESULTS
  Neither KIR repertoires nor HLA alleles were associated with HIV acquisition. However, KIR haplotype BB was associated with lower viral loads (-0.44 log10 copies/ml; SE = 0.18; p = 0.03) and higher CD4+ T-cell counts (+80 cells/μl; SE = 42; p = 0.04). This was largely explained by the protective effect of KIR2DL2/KIR2DS2 on the B haplotype and reciprocal detrimental effect of KIR2DL3 on the A haplotype.
  
  
  CONCLUSIONS
  Although neither KIR nor HLA appear to have a role in HIV acquisition, our data are consistent with involvement of KIR2DL2 in HIV control. Additional studies to replicate these findings are indicated.
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa. vivekn@well.ox.ac.uk.|Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. vivekn@well.ox.ac.uk.|HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa. vivekn@well.ox.ac.uk.
authors.forename: V
authors.initials: V
authors.lastname: Naranbhai
authors.affiliation: National Institute of Communicable Diseases, Sandringham, South Africa. debradeassisrosa@gmail.com.|University of the Witwatersrand, Johannesburg, South Africa. debradeassisrosa@gmail.com.
authors.forename: D
authors.initials: D
authors.lastname: de Assis Rosa
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa. liesiew@gmail.com.
authors.forename: L
authors.initials: L
authors.lastname: Werner
authors.affiliation: HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa. ramony111@gmail.com.
authors.forename: R
authors.initials: R
authors.lastname: Moodley
authors.affiliation: Division of Virology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. heatherh@nicd.ac.za.
authors.forename: H
authors.initials: H
authors.lastname: Hong
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa. KHARSANY@ukzn.ac.za.
authors.forename: A
authors.initials: A
authors.lastname: Kharsany
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa. mlisanak@gmail.com.
authors.forename: K
authors.initials: K
authors.lastname: Mlisana
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa. singeziwe@yahoo.com.
authors.forename: S
authors.initials: S
authors.lastname: Sibeko
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa. Nigel.Garrett@caprisa.org.
authors.forename: N
authors.initials: N
authors.lastname: Garrett
authors.affiliation: University of Cape Town, Cape Town, South Africa. denis.chopera@gmail.com.
authors.forename: D
authors.initials: D
authors.lastname: Chopera
authors.affiliation: HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa. wcarr@mec.cuny.edu.|City University of New York - Medgar Evers College, New York, USA. wcarr@mec.cuny.edu.|Ragon Institute of MGH, MIT and Harvard University, Boston, USA. wcarr@mec.cuny.edu.
authors.forename: W H
authors.initials: WH
authors.lastname: Carr
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa. Quarraisha.AbdoolKarim@caprisa.org.|Mailman School of Public Health, Columbia University, New York, USA. Quarraisha.AbdoolKarim@caprisa.org.
authors.forename: Q
authors.initials: Q
authors.lastname: Abdool Karim
authors.affiliation: Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. adrian.hill@ndm.ox.ac.uk.
authors.forename: A V S
authors.initials: AV
authors.lastname: Hill
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa. Salim.AbdoolKarim@caprisa.org.|Mailman School of Public Health, Columbia University, New York, USA. Salim.AbdoolKarim@caprisa.org.
authors.forename: S S
authors.initials: SS
authors.lastname: Abdool Karim
authors.affiliation: Ragon Institute of MGH, MIT and Harvard University, Boston, USA. marcus.altfeld@hpi.uni-hamburg.de.|Leibniz Institute for Experimental Virology, Heinrich Pette Institute, Hamburg, Germany. marcus.altfeld@hpi.uni-hamburg.de.
authors.forename: M
authors.initials: M
authors.lastname: Altfeld
authors.affiliation: National Institute of Communicable Diseases, Sandringham, South Africa. clive.gray@uct.ac.za.|University of Cape Town, Cape Town, South Africa. clive.gray@uct.ac.za.
authors.forename: C M
authors.initials: CM
authors.lastname: Gray
authors.affiliation: HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa. ndungu@ukzn.ac.za.|Ragon Institute of MGH, MIT and Harvard University, Boston, USA. ndungu@ukzn.ac.za.|KwaZulu-Natal Research Institute for Tuberculosis and HIV, University of KwaZulu-Natal, Durban, South Africa. ndungu@ukzn.ac.za.|Max Planck Institute for Infection Biology, Chariteplatz, D-10117, Berlin, Germany. ndungu@ukzn.ac.za.
authors.forename: T
authors.initials: T
authors.lastname: Ndung'u
mesh_terms: D000328:Adult; D000483:Alleles; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000276:immunology*; D015236:HLA-C Antigens; D006239:Haplotypes; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D011446:Prospective Studies; D054340:Receptors, KIR / Q000235:genetics*; D013019:South Africa; D019562:Viral Load
chemical_list: D015236:HLA-C Antigens; D054340:Receptors, KIR
references.citation: J Infect Dis. 2012 Oct 1;206(7):993-1001
references.pmid: 22829639
references.citation: Clin Infect Dis. 2014 Nov 1;59(9):1322-31
references.pmid: 25038116
references.citation: Tissue Antigens. 2011 Sep;78(3):185-94
references.pmid: 21810083
references.citation: PLoS Pathog. 2013;9(7):e1003515
references.pmid: 23935489
references.citation: J Virol. 2008 Oct;82(19):9668-77
references.pmid: 18579582
references.citation: PLoS Pathog. 2011 Oct;7(10):e1002270
references.pmid: 22022261
references.citation: Science. 2010 Sep 3;329(5996):1168-74
references.pmid: 20643915
references.citation: Blood. 2007 May 15;109(10):4296-305
references.pmid: 17272507
references.citation: Science. 2013 Apr 5;340(6128):87-91
references.pmid: 23559252
references.citation: AIDS Behav. 2015 Jul;19(7):1305-16
references.pmid: 25662962
references.citation: PLoS Pathog. 2012;8(7):e1002805
references.pmid: 22807681
references.citation: PLoS One. 2011;6(2):e16541
references.pmid: 21346814
references.citation: Clin Immunol. 2010 Feb;134(2):158-68
references.pmid: 19880352
references.citation: Nat Rev Immunol. 2013 Jul;13(7):487-98
references.pmid: 23797064
references.citation: PLoS One. 2008;3(4):e1954
references.pmid: 18414658
references.citation: Eur J Immunol. 2015 Feb;45(2):492-500
references.pmid: 25359276
references.citation: J Immunol. 2009 Jan 1;182(1):92-101
references.pmid: 19109139
references.citation: Nat Genet. 2002 Aug;31(4):429-34
references.pmid: 12134147
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12879-84
references.pmid: 19561305
references.citation: J Acquir Immune Defic Syndr. 2015 Jan 1;68(1):55-61
references.pmid: 25247433
references.citation: J Infect Dis. 2007 May 15;195(10):1452-60
references.pmid: 17436225
references.citation: J Infect Dis. 2011 Feb 15;203(4):487-95
references.pmid: 21216870
references.citation: J Exp Med. 2007 Nov 26;204(12):3027-36
references.pmid: 18025129
references.citation: AIDS. 2009 Jan 14;23(2):161-75
references.pmid: 19098485
references.citation: N Engl J Med. 2000 Sep 7;343(10):702-9
references.pmid: 10974135
references.citation: AIDS. 2008 Mar 12;22(5):595-9
references.pmid: 18317000
references.citation: AIDS. 2012 Sep 10;26(14):1745-53
references.pmid: 22781225
references.citation: PLoS One. 2013;8(1):e53251
references.pmid: 23326405
references.citation: Annu Rev Med. 2013;64:203-17
references.pmid: 23020875
references.citation: J Immunol. 2003 Dec 1;171(11):5663-7
references.pmid: 14634071
references.citation: Blood. 2011 Dec 8;118(24):6387-91
references.pmid: 22031859
references.citation: Methods Mol Biol. 2012;882:391-414
references.pmid: 22665247
references.citation: Front Immunol. 2012 Nov 22;3:336
references.pmid: 23189078
references.citation: Mol Immunol. 2005 Feb;42(4):557-60
references.pmid: 15607813
references.citation: J Immunol. 2006 Nov 15;177(10):6588-92
references.pmid: 17082569
references.citation: Immunogenetics. 2001;52(3-4):195-205
references.pmid: 11220621
references.citation: AIDS Behav. 2012 Oct;16(7):1870-6
references.pmid: 22618892
references.citation: Eur J Immunol. 2014 Oct;44(10):2938-48
references.pmid: 25043727
references.citation: Blood. 2012 Nov 22;120(22):4317-23
references.pmid: 23002117
references.citation: Blood. 2009 Sep 24;114(13):2667-77
references.pmid: 19553639
references.citation: Nat Genet. 2009 Dec;41(12):1290-4
references.pmid: 19935663
references.citation: Hum Mol Genet. 2013 May 1;22(9):1903-10
references.pmid: 23372042
references.citation: Science. 2007 Aug 17;317(5840):944-7
references.pmid: 17641165
references.citation: Nature. 2011 Aug 4;476(7358):96-100
references.pmid: 21814282
references.citation: Blood. 2014 Jan 30;123(5):678-86
references.pmid: 24326534
references.citation: Hepatology. 2010 Apr;51(4):1168-75
references.pmid: 20077564
references.citation: PLoS One. 2011;6(2):e17043
references.pmid: 21347267
references.citation: Blood. 2011 Jan 6;117(1):98-107
references.pmid: 20935255
references.citation: Viral Immunol. 2005;18(3):513-22
references.pmid: 16212530