title: Cervicovaginal HIV-1-neutralizing immunoglobulin A detected among HIV-1-exposed seronegative female partners in HIV-1-discordant couples.
abstract: OBJECTIVE
  Cervicovaginal HIV-1-neutralizing immunoglobulin A (IgA) was associated with reduced HIV-1 acquisition in a cohort of commercial sex workers. We aimed to define the prevalence and correlates of HIV-1-neutralizing IgA from HIV-1-exposed seronegative (HESN) women in HIV-1-serodiscordant relationships.
  
  
  METHODS
  HIV-1-serodiscordant couples in Nairobi were enrolled and followed quarterly up to 2 years, and women in concordant HIV-1-negative relationships were enrolled as controls. Cervicovaginal, seminal, and blood samples were collected at enrollment and follow-up. Cervicovaginal IgA was assessed for HIV-1-neutralizing activity by a peripheral blood mononuclear cell-based assay using an HIV-1 clade A primary isolate.
  
  
  RESULTS
  HESN women in discordant relationships had significantly more HIV-1-neutralizing IgA detected in genital secretions compared with control women [36 of 155 (23%) vs. four of 70 (6%), respectively; odds ratio (OR) 5.0; 95% confidence interval (CI) 1.70-14.64; P = 0.003]. These responses persisted over time in all available follow-up cervicovaginal samples from women with detectable HIV-1-neutralizing IgA at baseline. Partner median HIV-1 plasma viral load was lower among women who had HIV-1-neutralizing IgA compared with women without detectable activity (4.3 vs. 4.8 log(10) copies/ml, respectively; OR 0.70; 95% CI 0.51-0.94; P = 0.02). A similar trend was found with partner seminal viral load (OR 0.57; 95% CI 0.32-1.02; P = 0.06).
  
  
  CONCLUSIONS
  HESN women were five times more likely to have neutralizing IgA in cervicovaginal secretions than low-risk control women, and these responses were inversely associated with partner viral load. These observations support the existence of antiviral activity in the mucosal IgA fraction following sexual HIV-1 exposure.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98104, USA. ryc@u.washington.edu
authors.forename: Robert Y
authors.initials: RY
authors.lastname: Choi
authors.forename: Pauline
authors.initials: P
authors.lastname: Levinson
authors.forename: Brandon L
authors.initials: BL
authors.lastname: Guthrie
authors.forename: Barbara
authors.initials: B
authors.lastname: Lohman-Payne
authors.forename: Rose
authors.initials: R
authors.lastname: Bosire
authors.forename: Amy Y
authors.initials: AY
authors.lastname: Liu
authors.forename: Taha
authors.initials: T
authors.lastname: Hirbod
authors.forename: James
authors.initials: J
authors.lastname: Kiarie
authors.forename: Julie
authors.initials: J
authors.lastname: Overbaugh
authors.forename: Grace
authors.initials: G
authors.lastname: John-Stewart
authors.forename: Kristina
authors.initials: K
authors.lastname: Broliden
authors.forename: Carey
authors.initials: C
authors.lastname: Farquhar
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology*; D002584:Cervix Uteri / Q000276:immunology* / Q000821:virology; D005260:Female; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology* / Q000502:physiology; D007630:Kenya / Q000453:epidemiology; D008297:Male; D016017:Odds Ratio; D011446:Prospective Studies; D060386:Sex Workers / Q000706:statistics & numerical data; D012747:Sexual Partners; D014621:Vagina / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D019562:Viral Load
chemical_list: D057134:Antibodies, Neutralizing; D007070:Immunoglobulin A