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Breast milk cellular HIV-specific interferon ? responses are associated with protection from peripartum HIV transmission.

ABSTRACT: 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.A prospective study was designed to measure associations between maternal breast milk HIV-specific interferon-? (IFN-?) responses and infant HIV-1 detection at 1 month of age.In a Kenyan cohort of HIV-infected mothers, blood and breast milk HIV-gag IFN-? ELISpot responses were measured. Logistic regression was used to measure associations between breast milk IFN-? responses and infant HIV infection at 1 month of age.IFN-? responses were detected in breast milk from 117 of 170 (69%) women. IFN-? responses were associated with breast milk viral load, levels of macrophage inflammatory protein (MIP) 1?, MIP-1?, 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-? response (P = 0.08, P = 0.04, respectively), breast milk MIP-1? 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-1?, breast milk IFN-? 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).These data show breast milk HIV-gag-specific IFN-? 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.

SUBMITTER: Lohman-Payne B

PROVIDER: S-EPMC3718292 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Breast milk cellular HIV-specific interferon γ responses are associated with protection from peripartum HIV transmission.

Lohman-Payne Barbara B Slyker Jennifer A JA Moore Stephen S Maleche-Obimbo Elizabeth E Wamalwa Dalton C DC Richardson Barbra A BA Rowland-Jones Sarah S Mbori-Ngacha Dorothy D Farquhar Carey C Overbaugh Julie J John-Stewart Grace G

AIDS (London, England) 20121001 16

<h4>Objective</h4>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.<h4>Design</h4>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.<h4>Methods</h4>In a Kenyan cohort o ...[more]

PMID: 22948269

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Project description:Infants born to HIV-1-infected mothers in resource-limited areas where replacement feeding is unsafe and impractical are repeatedly exposed to HIV-1 throughout breastfeeding. Despite this, the majority of infants do not contract HIV-1 postnatally, even in the absence of maternal antiretroviral therapy. This suggests that immune factors in breast milk of HIV-1-infected mothers help to limit vertical transmission. We compared the HIV-1 envelope-specific breast milk and plasma antibody responses of clade C HIV-1-infected postnatally transmitting and nontransmitting mothers in the control arm of the Malawi-based Breastfeeding Antiretrovirals and Nutrition Study using multivariable logistic regression modeling. We found no association between milk or plasma neutralization activity, antibody-dependent cell-mediated cytotoxicity, or HIV-1 envelope-specific IgG responses and postnatal transmission risk. While the envelope-specific breast milk and plasma IgA responses also did not reach significance in predicting postnatal transmission risk in the primary model after correction for multiple comparisons, subsequent exploratory analysis using two distinct assay methodologies demonstrated that the magnitudes of breast milk total and secretory IgA responses against a consensus HIV-1 envelope gp140 (B.con env03) were associated with reduced postnatal transmission risk. These results suggest a protective role for mucosal HIV-1 envelope-specific IgA responses in the context of postnatal virus transmission. This finding supports further investigations into the mechanisms by which mucosal IgA reduces risk of HIV-1 transmission via breast milk and into immune interventions aimed at enhancing this response.Infants born to HIV-1-infected mothers are repeatedly exposed to the virus in breast milk. Remarkably, the transmission rate is low, suggesting that immune factors in the breast milk of HIV-1-infected mothers help to limit transmission. We compared the antibody responses in plasma and breast milk of HIV-1-transmitting and -nontransmitting mothers to identify responses that correlated with reduced risk of postnatal HIV-1 transmission. We found that neither plasma nor breast milk IgG antibody responses were associated with risk of HIV-1 transmission. In contrast, the magnitudes of the breast milk IgA and secretory IgA responses against HIV-1 envelope proteins were associated with reduced risk of postnatal HIV-1 transmission. The results of this study support further investigations of the mechanisms by which mucosal IgA may reduce the risk of HIV-1 transmission via breastfeeding and the development of strategies to enhance milk envelope-specific IgA responses to reduce mother-to-child HIV transmission and promote an HIV-free generation.

Dataset Information

Breast milk cellular HIV-specific interferon ? responses are associated with protection from peripartum HIV transmission.

Publications

Breast milk cellular HIV-specific interferon γ responses are associated with protection from peripartum HIV transmission.

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