title: Innate Antibacterial Activity in Female Genital Tract Secretions Is Associated with Increased Risk of HIV Acquisition.
abstract: Greater inhibitory activity against Escherichia coli and levels of human β defensin (HBD)-2 in genital tract secretions predicted HIV acquisition in women in the HPTN 035 trial. We investigated whether higher levels of E. coli inhibitory activity and antimicrobial peptides in cervicovaginal lavage (CVL) samples predicted HIV acquisition in women in the CAPRISA 002 Acute Infection Study. E. coli inhibitory activity and antimicrobial peptides were quantified in CVL from a subset of CAPRISA 002 participants who did not seroconvert (n=39) and from seroconverting women prior to infection (n=17) and during acute infection (n=11). Women who acquired HIV had significantly greater preinfection CVL E. coli inhibitory activity (p=0.01) and HBD-1 levels (p=0.02) compared to women who remained uninfected. Preinfection E. coli inhibitory activity remained significantly associated with seroconversion following adjustment for the presence of bacterial vaginosis (OR 1.45; 95% CI 1.07, 1.97). Partial least squares discriminant analysis confirmed that preinfection CVL E. coli inhibitory activity, together with higher CVL concentrations of HBD-1 and secretory leukocyte protease inhibitor, distinguished seroconverters from nonseroconverters with 67% calibration accuracy. CVL concentrations of human neutrophil peptides (HNP) 1-3 increased significantly with acute infection (p=0.001) and correlated with plasma viral set point (r=0.66, p=0.03). E. coli inhibitory activity in genital tract secretions could provide a biomarker of HIV risk. The correlation between HNP 1-3 and viral set point merits further investigation of the relationship between mucosal inflammation during early HIV infection and disease progression.
authors.affiliation: 1 Department of Pediatrics, Albert Einstein College of Medicine , Bronx, New York.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pellett Madan
authors.affiliation: 2 Institute of Infectious Diseases and Molecular Medicine, University of Cape Town , Cape Town, South Africa .|3 Centre for the AIDS Programme of Research in South Africa (CAPRISA) , Durban, South Africa .
authors.forename: Lindi
authors.initials: L
authors.lastname: Masson
authors.affiliation: 1 Department of Pediatrics, Albert Einstein College of Medicine , Bronx, New York.
authors.forename: Jessica
authors.initials: J
authors.lastname: Tugetman
authors.affiliation: 3 Centre for the AIDS Programme of Research in South Africa (CAPRISA) , Durban, South Africa .
authors.forename: Lise
authors.initials: L
authors.lastname: Werner
authors.affiliation: 3 Centre for the AIDS Programme of Research in South Africa (CAPRISA) , Durban, South Africa .
authors.forename: Anneke
authors.initials: A
authors.lastname: Grobler
authors.affiliation: 3 Centre for the AIDS Programme of Research in South Africa (CAPRISA) , Durban, South Africa .|4 Nelson R. Mandela School of Medicine, University of KwaZulu-Natal , Durban, South Africa .|5 Department of Medical Microbiology, National Health Laboratory Service , Durban, South Africa .
authors.forename: Koleka
authors.initials: K
authors.lastname: Mlisana
authors.affiliation: 6 Department of Epidemiology and Population Health, Albert Einstein College of Medicine , Bronx, New York.
authors.forename: Yungtai
authors.initials: Y
authors.lastname: Lo
authors.affiliation: 7 Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts.
authors.forename: Denise
authors.initials: D
authors.lastname: Che
authors.affiliation: 7 Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts.
authors.forename: Kelly B
authors.initials: KB
authors.lastname: Arnold
authors.affiliation: 3 Centre for the AIDS Programme of Research in South Africa (CAPRISA) , Durban, South Africa .|4 Nelson R. Mandela School of Medicine, University of KwaZulu-Natal , Durban, South Africa .
authors.forename: Salim S
authors.initials: SS
authors.lastname: Abdool Karim
authors.affiliation: 2 Institute of Infectious Diseases and Molecular Medicine, University of Cape Town , Cape Town, South Africa .|3 Centre for the AIDS Programme of Research in South Africa (CAPRISA) , Durban, South Africa .
authors.forename: Jo-Ann S
authors.initials: JA
authors.lastname: Passmore
authors.affiliation: 1 Department of Pediatrics, Albert Einstein College of Medicine , Bronx, New York.
authors.forename: Betsy C
authors.initials: BC
authors.lastname: Herold
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000032:analysis; D012634:Bodily Secretions / Q000276:immunology*; D004198:Disease Susceptibility; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D005836:Genitalia, Female / Q000276:immunology*; D015658:HIV Infections / Q000453:epidemiology* / Q000635:transmission*; D006801:Humans; D007113:Immunity, Innate; D018570:Risk Assessment
chemical_list: D023181:Antimicrobial Cationic Peptides