Breast milk alpha-defensins are associated with HIV type 1 RNA and CC chemokines in breast milk but not vertical HIV type 1 transmission.
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.
Bosire
Rose
R
Department of Pediatrics, University of Nairobi, Nairobi, Kenya.
John-Stewart
Grace C
GC
Mabuka
Jennifer M
JM
Wariua
Grace
G
Gichuhi
Christine
C
Wamalwa
Dalton
D
Ruzinski
John
J
Goodman
Richard
R
Lohman
Barbara
B
Mbori-Ngacha
Dorothy A
DA
Overbaugh
Julie
J
Farquhar
Carey
C
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*
D019742:Chemokines, CC; D019743:Chemokines, CXC; D023084:alpha-Defensins