title: Breast milk alpha-defensins are associated with HIV type 1 RNA and CC chemokines in breast milk but not vertical HIV type 1 transmission.
abstract: Alpha-defensins are proteins exhibiting in vitro anti-HIV-1 activity that may protect against mother-to-child transmission of HIV-1 via breast milk. Correlates of alpha-defensins in breast milk and transmission risk were determined in a cohort of HIV-1-infected pregnant women in Nairobi followed for 12 months postpartum with their infants. Maternal blood was collected antenatally and at delivery for HIV-1 viral load and infant HIV-1 infection status was determined < 48 h after birth and at months 1, 3, 6, 9, and 12. Breast milk specimens collected at month 1 were assayed for alpha-defensins, HIV-1 RNA, subclinical mastitis, and CC and CXC chemokines. We detected alpha-defensins in breast milk specimens from 108 (42%) of 260 HIV-1-infected women. Women with detectable alpha-defensins (> or =50 pg/ml) had a median concentration of 320 pg/ml and significantly higher mean breast milk HIV-1 RNA levels than women with undetectable alpha-defensins (2.9 log(10) copies/ml versus 2.5 log(10) copies/ml, p = 0.003). Increased alpha-defensins concentrations in breast milk were also associated with subclinical mastitis (Na (+)/K(+) ratio > 1) and increased breast milk chemokine levels. Overall, 40 (15%) infants were HIV-1 uninfected at birth and subsequently acquired HIV-1. There was no significant association between month 1 alpha-defensins and risk of HIV-1 transmission. In conclusion, alpha-defensins were associated with breast milk HIV-1 viral load, chemokine levels, and subclinical mastitis, all of which may alter risk of infant HIV-1 acquisition. Despite these associations there was no significant relationship between breast milk alpha-defensins and mother-to-child transmission, suggesting a complex interplay between breast milk HIV-1, inflammation, and antiinfective factors.
authors.affiliation: Department of Pediatrics, University of Nairobi, Nairobi, Kenya.
authors.forename: Rose
authors.initials: R
authors.lastname: Bosire
authors.forename: Grace C
authors.initials: GC
authors.lastname: John-Stewart
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Mabuka
authors.forename: Grace
authors.initials: G
authors.lastname: Wariua
authors.forename: Christine
authors.initials: C
authors.lastname: Gichuhi
authors.forename: Dalton
authors.initials: D
authors.lastname: Wamalwa
authors.forename: John
authors.initials: J
authors.lastname: Ruzinski
authors.forename: Richard
authors.initials: R
authors.lastname: Goodman
authors.forename: Barbara
authors.initials: B
authors.lastname: Lohman
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: Mbori-Ngacha
authors.forename: Julie
authors.initials: J
authors.lastname: Overbaugh
authors.forename: Carey
authors.initials: C
authors.lastname: Farquhar
mesh_terms: D000293:Adolescent; D000328:Adult; D019742:Chemokines, CC / Q000032:analysis; D019743:Chemokines, CXC / Q000032:analysis; D005260:Female; D015658:HIV Infections / Q000635:transmission*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D007630:Kenya; D008895:Milk, Human / Q000276:immunology* / Q000821:virology; D011247:Pregnancy; D011446:Prospective Studies; D019562:Viral Load; D023084:alpha-Defensins / Q000032:analysis / Q000276:immunology*
chemical_list: D019742:Chemokines, CC; D019743:Chemokines, CXC; D023084:alpha-Defensins