CC and CXC chemokines in breastmilk are associated with mother-to-child HIV-1 transmission

Curr HIV Res. 2005 Oct;3(4):361-9. doi: 10.2174/157016205774370393.

Abstract

Introduction: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5 / analysis
  • Chemokine CXCL12
  • Chemokines, CC / isolation & purification*
  • Chemokines, CXC / analysis
  • Chemokines, CXC / isolation & purification*
  • Cohort Studies
  • Female
  • HIV Infections / transmission*
  • Humans
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical*
  • Longitudinal Studies
  • Macrophage Inflammatory Proteins / analysis
  • Milk, Human / chemistry*
  • RNA, Viral / analysis
  • Risk Factors

Substances

  • CXCL12 protein, human
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokine CXCL12
  • Chemokines, CC
  • Chemokines, CXC
  • Macrophage Inflammatory Proteins
  • RNA, Viral