CC and CXC chemokines in breastmilk are associated with mother-to-child HIV-1 transmission.
BACKGROUND
CC and CXC chemokines may play a role in mother-to-child HIV-1 transmission by blocking HIV-1 binding to chemokine receptors and impeding viral entry into cells.


METHODS
To define correlates of breastmilk chemokines and associations with infant HIV-1 acquisition, chemokines in breastmilk and infant HIV-1 infection risk were assessed in an observational, longitudinal cohort study. We measured MIP-1alpha, MIP-1beta, RANTES, and SDF-1 in month 1 breastmilk specimens from HIV-1-infected women in Nairobi and HIV-1 viral load was calculated in maternal plasma and breastmilk at delivery and 1 month postpartum. Infant infection status was determined at birth and months 1, 3, 6, 9, and 12.


RESULTS
Among 281 breastfeeding women, 60 (21%) of their infants acquired HIV-1 during follow-up, 39 (65%) of whom became infected intrapartum or after birth. MIP-1alpha, MIP-1beta, RANTES, and SDF-1 were all positively correlated with breastmilk HIV-1 RNA (P<0.0005). Women with clinical mastitis had 50% higher MIP-1alpha and MIP-1beta levels (P<0.001 and P=0.006, respectively) and women with subclinical mastitis (breastmilk Na(+)/K(+)>1) had approximately 70% higher MIP-1alpha, MIP-1beta and RANTES (P<0.002 for all) compared to women without mastitis. Independent of breastmilk HIV-1, increased MIP-1beta and SDF-1 were associated with reduced risk of infant HIV-1 (RR=0.4; 95% CI 0.2-0.9; P=0.03 and RR=0.5; 95% CI=0.3-0.9; P=0.02, respectively) and increased RANTES was associated with higher transmission risk (RR=2.3; 95% CI 1.1- 5.3; P=0.04).


CONCLUSIONS
These observations suggest a complex interplay between virus levels, breastmilk chemokines, and mother-to-child HIV-1 transmission and may provide insight into developing novel strategies to reduce infection across mucosal surfaces.
Farquhar
Carey
C
Department of Medicine, University of Washington, Seattle, 98104, USA. cfarq@u.washington.edu
Mbori-Ngacha
Dorothy A
DA
Redman
Mary W
MW
Bosire
Rose K
RK
Lohman
Barbara L
BL
Piantadosi
Anne L
AL
Goodman
Richard B
RB
Ruzinski
John T
JT
Emery
Sandy R
SR
Crudder
Christopher H
CH
Overbaugh
Julie M
JM
John-Stewart
Grace C
GC
D000293:Adolescent; D000328:Adult; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000032:analysis; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000302:isolation & purification*; D019743:Chemokines, CXC / Q000032:analysis / Q000302:isolation & purification*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000635:transmission*; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008137:Longitudinal Studies; D019402:Macrophage Inflammatory Proteins / Q000032:analysis; D008895:Milk, Human / Q000737:chemistry*; D012367:RNA, Viral / Q000032:analysis; D012307:Risk Factors
C515255:CXCL12 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; D019402:Macrophage Inflammatory Proteins; D012367:RNA, Viral