title: Breast milk cellular HIV-specific interferon γ responses are associated with protection from peripartum HIV transmission.
abstract: OBJECTIVE
  Breast milk is a major route of infant HIV infection, yet the majority of breast-fed, HIV-exposed infants escape infection by unknown mechanisms. This study aimed to investigate the role of HIV-specific breast milk cells in preventing infant HIV infection.
  
  
  METHODS
  A prospective study was designed to measure associations between maternal breast milk HIV-specific interferon-γ (IFN-γ) responses and infant HIV-1 detection at 1 month of age.
  
  
  METHODS
  In a Kenyan cohort of HIV-infected mothers, blood and breast milk HIV-gag IFN-γ ELISpot responses were measured. Logistic regression was used to measure associations between breast milk IFN-γ responses and infant HIV infection at 1 month of age.
  
  
  RESULTS
  IFN-γ responses were detected in breast milk from 117 of 170 (69%) women. IFN-γ responses were associated with breast milk viral load, levels of macrophage inflammatory protein (MIP) 1α, MIP-1β, regulated upon activation, normal T-cell expressed, and secreted and stromal-cell derived factor 1 and subclinical mastitis. Univariate factors associated with infant HIV infection at 1 month postpartum included both detection and breadth of breast milk IFN-γ response (P = 0.08, P = 0.04, respectively), breast milk MIP-1β detection (P = 0.05), and plasma (P = 0.004) and breast milk (P = 0.004) viral load. In multivariate analyses adjusting for breast milk viral load and MIP-1β, breast milk IFN-γ responses were associated with an approximately 70% reduction in infant HIV infection [adjusted odds ratio (aOR) 0.29, 95% confidence interval (CI) 0.092-0.91], and each additional peptide pool targeted was associated with an approximately 35% reduction in infant HIV (aOR 0.65, 95% CI 0.44-0.97).
  
  
  CONCLUSIONS
  These data show breast milk HIV-gag-specific IFN-γ cellular immune responses are prevalent and may contribute to protection from early HIV transmission. More broadly, these data suggest breast milk cellular responses are potentially influential in decreasing mother-to-child transmission of viruses.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA. bll@u.washington.edu
authors.forename: Barbara
authors.initials: B
authors.lastname: Lohman-Payne
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Slyker
authors.forename: Stephen
authors.initials: S
authors.lastname: Moore
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Maleche-Obimbo
authors.forename: Dalton C
authors.initials: DC
authors.lastname: Wamalwa
authors.forename: Barbra A
authors.initials: BA
authors.lastname: Richardson
authors.forename: Sarah
authors.initials: S
authors.lastname: Rowland-Jones
authors.forename: Dorothy
authors.initials: D
authors.lastname: Mbori-Ngacha
authors.forename: Carey
authors.initials: C
authors.lastname: Farquhar
authors.forename: Julie
authors.initials: J
authors.lastname: Overbaugh
authors.forename: Grace
authors.initials: G
authors.lastname: John-Stewart
mesh_terms: D000328:Adult; D001942:Breast Feeding; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006679:HIV Seropositivity / Q000276:immunology* / Q000635:transmission*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control* / Q000706:statistics & numerical data; D007371:Interferon-gamma / Q000096:biosynthesis*; D007630:Kenya / Q000453:epidemiology; D008297:Male; D008895:Milk, Human / Q000276:immunology / Q000821:virology*; D058725:Peripartum Period / Q000276:immunology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology / Q000276:immunology*; D011446:Prospective Studies; D019562:Viral Load
chemical_list: D007371:Interferon-gamma