title: Distinct genital tract HIV-specific antibody profiles associated with tenofovir gel.
abstract: The impact of topical antiretrovirals for pre-exposure prophylaxis on humoral responses following HIV infection is unknown. Using a binding antibody multiplex assay, we investigated HIV-specific IgG and IgA responses to envelope glycoproteins, p24 Gag and p66, in the genital tract (GT) and plasma following HIV acquisition in women assigned to tenofovir gel (n=24) and placebo gel (n=24) in the CAPRISA 004 microbicide trial to assess if this topical antiretroviral had an impact on mucosal and systemic antibody responses. Linear mixed effect modeling and partial least squares discriminant analysis was used to identify multivariate antibody signatures associated with tenofovir use. There were significantly higher response rates to gp120 Env (P=0.03), p24 (P=0.002), and p66 (P=0.009) in plasma and GT in women assigned to tenofovir than placebo gel at multiple time points post infection. Notably, p66 IgA titers in the GT and plasma were significantly higher in the tenofovir compared with the placebo arm (P<0.05). Plasma titers for 9 of the 10 HIV-IgG specificities predicted GT levels. Taken together, these data suggest that humoral immune responses are increased in blood and GT of individuals who acquire HIV infection in the presence of tenofovir gel.
authors.affiliation: Centre for the AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: D
authors.initials: D
authors.lastname: Archary
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Seaton
authors.affiliation: Centre for the AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.|Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.|National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg, South Africa.
authors.forename: J S
authors.initials: JS
authors.lastname: Passmore
authors.affiliation: Centre for the AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: L
authors.initials: L
authors.lastname: Werner
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: A
authors.initials: A
authors.lastname: Deal
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Dunphy
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: K B
authors.initials: KB
authors.lastname: Arnold
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Yates
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Lauffenburger
authors.affiliation: Imperial College, International AIDS Vaccine Initiative Core Immune Monitoring Laboratory, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Bergin
authors.affiliation: Centre for the AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: L J
authors.initials: LJ
authors.lastname: Liebenberg
authors.affiliation: Centre for the AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: N
authors.initials: N
authors.lastname: Samsunder
authors.affiliation: KAVI Institute of Clinical Research, School of Medicine, College of Health Sciences, University of Nairobi, Nairobi, Kenya.
authors.forename: M W
authors.initials: MW
authors.lastname: Mureithi
authors.affiliation: Heinrich-Pette Institut, Leibniz Institute for Experimental Virology, University of Hamburg, Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Altfeld
authors.affiliation: Centre for the AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: N
authors.initials: N
authors.lastname: Garrett
authors.affiliation: Centre for the AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.|Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors.forename: Q Abdool
authors.initials: QA
authors.lastname: Karim
authors.affiliation: Centre for the AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.|Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors.forename: Ss Abdool
authors.initials: SA
authors.lastname: Karim
authors.affiliation: Centre for the AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.|National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg, South Africa.
authors.forename: L
authors.initials: L
authors.lastname: Morris
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.|Departments of Surgery, Immunology and Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Tomaras
mesh_terms: D000287:Administration, Topical; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005836:Genitalia, Female / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015483:HIV Antibodies / Q000378:metabolism*; D016655:HIV Core Protein p24 / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D054303:HIV Reverse Transcriptase / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism; D000068698:Tenofovir / Q000627:therapeutic use*; D016896:Treatment Outcome; D014622:Vaginal Creams, Foams, and Jellies; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014622:Vaginal Creams, Foams, and Jellies; C514793:gp120 protein, Human immunodeficiency virus 1; C514799:p24 protein, Human Immunodeficiency Virus Type 1; D000068698:Tenofovir; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase
references.citation: J Infect Dis. 2015 Sep 1;212(5):754-9
references.pmid: 25712973
references.citation: J Immunol. 2000 Nov 1;165(9):5170-6
references.pmid: 11046049
references.citation: AIDS. 2001 Feb 16;15(3):431-2
references.pmid: 11273233
references.citation: J Immunoassay Immunochem. 2002;23(2):145-62
references.pmid: 12033640
references.citation: Microbes Infect. 2002 May;4(6):667-77
references.pmid: 12048036
references.citation: Science. 2002 Jun 28;296(5577):2354-60
references.pmid: 12089434
references.citation: J Med Virol. 2002 Jul;67(3):320-6
references.pmid: 12116021
references.citation: J Acquir Immune Defic Syndr. 2002 Aug 1;30(4):413-20
references.pmid: 12138348
references.citation: Curr Opin Infect Dis. 2003 Feb;16(1):43-9
references.pmid: 12821829
references.citation: Expert Rev Vaccines. 2004 Aug;3(4 Suppl):S65-73
references.pmid: 15285706
references.citation: Nat Med. 1997 Nov;3(11):1250-7
references.pmid: 9359700
references.citation: J Immunol. 2004 Dec 1;173(11):7078-89
references.pmid: 15557206
references.citation: J Virol. 2005 Jan;79(2):1154-63
references.pmid: 15613343
references.citation: J Immunol. 2005 Feb 15;174(4):2185-9
references.pmid: 15699150
references.citation: Immunol Rev. 2005 Aug;206:64-82
references.pmid: 16048542
references.citation: Science. 2005 Dec 9;310(5754):1646-53
references.pmid: 16339439
references.citation: Clin Infect Dis. 2006 Mar 1;42(5):700-8
references.pmid: 16447118
references.citation: Nat Rev Immunol. 2006 Feb;6(2):148-58
references.pmid: 16491139
references.citation: Virology. 2006 Sep 30;353(2):268-82
references.pmid: 17039602
references.citation: Nature. 2007 Sep 6;449(7158):101-4
references.pmid: 17805298
references.citation: J Infect Dis. 2008 Sep 1;198(5):710-4
references.pmid: 18643751
references.citation: PLoS Med. 2008 Aug 5;5(8):e157; discussion e157
references.pmid: 18684007
references.citation: J Virol. 2008 Dec;82(24):12449-63
references.pmid: 18842730
references.citation: J Immunol. 2009 Mar 15;182(6):3718-27
references.pmid: 19265150
references.citation: Mucosal Immunol. 2009 Sep;2(5):412-26
references.pmid: 19587640
references.citation: J Virol. 2010 Jul;84(14):7161-73
references.pmid: 20444898
references.citation: Science. 2010 Sep 3;329(5996):1168-74
references.pmid: 20643915
references.citation: Curr Opin HIV AIDS. 2010 Sep;5(5):397-403
references.pmid: 20978380
references.citation: N Engl J Med. 2010 Dec 30;363(27):2587-99
references.pmid: 21091279
references.citation: Am J Reprod Immunol. 2011 Mar;65(3):361-7
references.pmid: 21087333
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4388-93
references.pmid: 21368166
references.citation: Sci Signal. 2011;4(165):ra16
references.pmid: 21427409
references.citation: PLoS One. 2011;6(4):e19295
references.pmid: 21541293
references.citation: Sci Transl Med. 2011 May 4;3(81):81ra36
references.pmid: 21543722
references.citation: J Acquir Immune Defic Syndr. 2011 Aug 15;57(5):355-62
references.pmid: 21637113
references.citation: PLoS One. 2011;6(9):e23532
references.pmid: 21980336
references.citation: AIDS. 2011 Nov 13;25(17):2089-97
references.pmid: 21832938
references.citation: Nature. 2012 Feb 2;482(7383):89-93
references.pmid: 22217938
references.citation: N Engl J Med. 2012 Apr 5;366(14):1275-86
references.pmid: 22475592
references.citation: J Acquir Immune Defic Syndr. 2012 Jun 1;60(2):124-7
references.pmid: 22362152
references.citation: N Engl J Med. 2012 Aug 2;367(5):399-410
references.pmid: 22784037
references.citation: J Infect Dis. 2012 Sep 1;206(5):770-9
references.pmid: 22740713
references.citation: PLoS Biol. 2012;10(9):e1001393
references.pmid: 23055830
references.citation: Immunity. 2013 Jan 24;38(1):176-86
references.pmid: 23313589
references.citation: AIDS. 2013 Feb 20;27(4):519-28
references.pmid: 23364441
references.citation: PLoS One. 2013;8(1):e55013
references.pmid: 23383037
references.citation: J Virol. 2013 Apr;87(8):4185-201
references.pmid: 23365441
references.citation: J Clin Invest. 2013 May;123(5):2183-92
references.pmid: 23563315
references.citation: Mucosal Immunol. 2013 Jul;6(4):692-703
references.pmid: 23299618
references.citation: Nature. 2013 Sep 5;501(7465):112-5
references.pmid: 23965619
references.citation: AIDS Res Hum Retroviruses. 2013 Nov;29(11):1443-50
references.pmid: 23600365
references.citation: Cell. 2013 Oct 24;155(3):531-9
references.pmid: 24243013
references.citation: PLoS Pathog. 2013;9(11):e1003776
references.pmid: 24278022
references.citation: PLoS One. 2013;8(12):e84185
references.pmid: 24358343
references.citation: PLoS One. 2014;9(2):e87572
references.pmid: 24504509
references.citation: Sci Transl Med. 2014 Mar 19;6(228):228ra39
references.pmid: 24648342
references.citation: PLoS One. 2014;9(7):e101863
references.pmid: 25054205
references.citation: J Immunol. 2014 Sep 15;193(6):3113-25
references.pmid: 25135832
references.citation: J Immunol. 2014 Sep 15;193(6):3126-33
references.pmid: 25143442
references.citation: Cell. 2014 Sep 11;158(6):1243-53
references.pmid: 25215485
references.citation: N Engl J Med. 2015 Feb 5;372(6):509-18
references.pmid: 25651245
references.citation: Vaccine. 2015 Apr 21;33(17):2086-95
references.pmid: 25769884
references.citation: Retrovirology. 2014;11:109
references.pmid: 25499540
references.citation: Immunity. 2015 May 19;42(5):965-76
references.pmid: 25992865
references.citation: Lancet Infect Dis. 2015 Jul;15(7):803-9
references.pmid: 26043884