Maternal Humoral Immune Responses Do Not Predict Postnatal HIV-1 Transmission Risk in Antiretroviral-Treated Mothers from the IMPAACT PROMISE Study
Loading...
Date
2019
Journal Title
Journal ISSN
Volume Title
Publisher
Msphere
Abstract
To design immune interventions that can synergize with antiretroviral
therapy (ART) to reduce the rate of HIV mother-to-child transmission (MTCT), it is essential
to characterize maternal immune responses in the setting of ART during
pregnancy and breastfeeding and define their effect on MTCT. Prior studies reported
an association between breast milk envelope (Env)-specific antibodies and antibodydependent
cell cytotoxicity (ADCC) activity with reduced postnatal transmission. In
this study, we investigated whether these immune correlates were similarly associated
with protection in a matched case-control study of mother-infant pairs receiving
maternal ART or infant nevirapine prophylaxis during breastfeeding in the
International Maternal-Pediatric-Adolescent AIDS Clinical Trials Network Promoting
Maternal-Infant Survival Everywhere (PROMISE) trial, assessing postnatal transmission
risk in 19 transmitting and 57 nontransmitting mothers using conditional logistic regression
models adjusted for maternal plasma viral load. The odds ratios of postnatal
MTCT for a 1-unit increase in an immune correlate were 3.61 (95% confidence interval
[CI], 0.56, 23.14) for breast milk Env-specific secretory IgA (sIgA), 2.32 (95% CI,
0.43, 12.56) for breast milk and 2.16 (95% CI, 0.51, 9.14) for plasma Env-specific IgA, and
4.57 (95% CI, 0.68, 30.48) for breast milk and 0.96 (95% CI, 0.25, 3.67) for plasma ADCC
activity, with all CIs spanning 1.0. Interestingly, although mucosal IgA responses are poor
in untreated HIV-infected women, there was a strong correlation between the magnitudes
of breast milk and plasma Env-specific IgA in this cohort. In this analysis of the
small number of postnatal virus transmissions in the landmark PROMISE study, no single
antibody response was associated with breast milk transmission risk.
Description
Keywords
ADCC, HIV-1, Antibodies, Antiretroviral therapy, Breast milk, Postnatal transmission
Citation
Hompe ED, Jacobson DL, Eudailey JA, Butler K, Edwards W, Pollara J, Brummel SS, Fouda GG, Chinula L, Kamanga M, Kinikar A, Moodley D, Owor M, Fowler MG, Permar SR. 2019. Maternal humoral immune responses do not predict postnatal HIV-1 transmission risk in antiretroviral-treated mothers from the IMPAACT PROMISE study. mSphere 4:e00716-19. https://doi.org/10.1128/mSphere .00716-19.