title: HIV-1-Neutralizing IgA Detected in Genital Secretions of Highly HIV-1-Exposed Seronegative Women on Oral Preexposure Prophylaxis.
abstract: Although nonhuman primate studies have shown that simian immunodeficiency virus/simian-human immunodeficiency virus (SIV/SHIV) exposure during preexposure prophylaxis (PrEP) with oral tenofovir can induce SIV immunity without productive infection, this has not been documented in humans. We evaluated cervicovaginal IgA in Partners PrEP Study participants using a subtype C primary isolate and found that women on PrEP had IgA with higher average human immunodeficiency virus type 1 (HIV-1)-neutralizing magnitude than women on placebo (33% versus 7%; P = 0.008). Using a cutoff of ≥90% HIV-1 neutralization, 19% of women on-PrEP had HIV-1-neutralizing IgA compared to 0% of women on placebo (P = 0.09). We also estimated HIV-1 exposure and found that the proportion of women with HIV-1-neutralizing IgA was associated with the level of HIV-1 exposure (P = 0.04). Taken together, our data suggest that PrEP and high levels of exposure to HIV may each enhance mucosal HIV-1-specific humoral immune responses in sexually exposed but HIV-1-uninfected individuals.
  
  
  OBJECTIVE
  Although there is not yet an effective HIV-1 vaccine, PrEP for at-risk HIV-1-uninfected individuals is a highly efficacious intervention to prevent HIV-1 acquisition and is currently being recommended by the CDC and WHO for all individuals at high risk of HIV-1 acquisition. We previously demonstrated that PrEP use does not enhance peripheral blood HIV-1-specific T-cell responses in HIV-exposed individuals. Here, we evaluate for cervicovaginal HIV-neutralizing IgA responses in genital mucosal secretions of HIV-exposed women, which is likely a more relevant site than peripheral blood for observation of potentially protective immune events occurring in response to sexual HIV-1 exposure for various periods. Furthermore, we assess for host response in the context of longitudinal quantification of HIV-1 exposure. We report that HIV-neutralizing IgA is significantly correlated with higher HIV-1 exposure and, furthermore, that there are more women with HIV-1-neutralizing IgA in the on-PrEP group than in the placebo group.
authors: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA Department of Global Health, University of Washington, Seattle, Washington, USA jlund@fredhutch.org.
authors: Jennifer M
authors: http://orcid.org/0000-0003-3284-979X
authors: JM
authors: Lund
authors: Department of Medicine, Karolinska Institute, Stockholm, Sweden.
authors: Kristina
authors: K
authors: Broliden
authors: Department of Global Health, University of Washington, Seattle, Washington, USA.
authors: Maria N
authors: MN
authors: Pyra
authors: Department of Global Health, University of Washington, Seattle, Washington, USA.
authors: Katherine K
authors: KK
authors: Thomas
authors: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA Department of Global Health, University of Washington, Seattle, Washington, USA.
authors: Deborah
authors: D
authors: Donnell
authors: Partners in Health Research and Development, Kenya Medical Research Institute, Thika, Kenya.
authors: Elizabeth
authors: E
authors: Irungu
authors: Infectious Disease Institute, Makerere University, Kampala, Uganda.
authors: Timothy R
authors: TR
authors: Muwonge
authors: Partners in Health Research and Development, Kenya Medical Research Institute, Thika, Kenya.
authors: Nelly
authors: N
authors: Mugo
authors: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Madhuri
authors: M
authors: Manohar
authors: Department of Laboratory Medicine, Lund University, Lund, Sweden.
authors: Marianne
authors: M
authors: Jansson
authors: Department of Global Health, University of Washington, Seattle, Washington, USA.
authors: Romel
authors: R
authors: Mackelprang
authors: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Mark A
authors: MA
authors: Marzinke
authors: Department of Global Health, University of Washington, Seattle, Washington, USA Department of Medicine, University of Washington, Seattle, Washington, USA Department of Epidemiology, University of Washington, Seattle, Washington, USA.
authors: Jared M
authors: JM
authors: Baeten
authors: Department of Global Health, University of Washington, Seattle, Washington, USA Department of Medicine, University of Washington, Seattle, Washington, USA Department of Pediatrics, University of Washington, Seattle, Washington, USA.
authors: Jairam R
authors: JR
authors: Lingappa
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D008137:Longitudinal Studies; D065129:Pre-Exposure Prophylaxis / Q000379:methods; D012725:Sexual Behavior
chemical_list: D057134:Antibodies, Neutralizing; D007070:Immunoglobulin A