Immune Activation Markers in Peripartum Women in Botswana: Association with Feeding Strategy and Maternal Morbidity
et al. (2014) Immune Activation Markers in Peripartum Women in Botswana: Association
with Feeding Strategy and Maternal Morbidity. PLoS ONE 9(3): e89928. doi:10.1371/journal.pone.0089928
Immune Activation Markers in Peripartum Women in Botswana: Association with Feeding Strategy and Maternal Morbidity
Elizabeth S. Russell 0
Terence Mohammed 0
Laura Smeaton 0
Baitshepi Jorowe 0
Iain J. MacLeod 0
Risa M. Hoffman 0
Judith S. Currier 0
Sikhulile Moyo 0
Max Essex 0
Shahin Lockman 0
Aftab A. Ansari, Emory University School of Medicine, United States of America
0 1 Harvard AIDS Initiative, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America, 2 Botswana-Harvard AIDS Institute, Gaborone, Botswana, 3 Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America, 4 David Geffen School of Medicine, University of California Los Angeles , Los Angeles , California, United States of America, 5 Department of Medicine, Division of Infectious Diseases, Brigham and Women's Hospital , Boston, Massachusetts , United States of America
Hormone levels shift the immune state in HIV-uninfected pregnant and breastfeeding women away from Th1 responses and toward regulation to permit fetal tolerance. Limited data exist on inflammation during pregnancy or postpartum in HIVinfected women, though certain inflammatory markers are associated with adverse health outcomes among HIV-infected persons. We measured hsCRP, D-dimer, IFN-c, IL-6, IL-10 and TNF-a at 34 weeks gestation and six months postpartum in HIV-infected women from the Botswana Mashi PMTCT trial who were randomized to breastfeeding or formula-feeding. Differences in inflammatory markers between gestation and postpartum periods, and by randomized feeding method, were estimated using generalized estimating equations, adjusting for baseline plasma HIV-1 viral load, CD4 count, calendar time, and antiretroviral treatment status. Additionally, we studied the association between marker concentrations at six months postpartum and major adverse clinical events over the following 4.5 years, using case-cohort sampling and adjusted Cox proportional hazards models. In 86 breastfeeding and 75 formula-feeding women, hsCRP and D-dimer decreased significantly between 34 weeks gestation and six months postpartum, while IFN-c increased. There was no significant association between inflammatory marker change and randomized feeding method after adjusting for multiple comparisons and removing outliers. In univariate analysis, TNF-a, D-dimer, and IFN-c concentrations at six months postpartum were significant predictors of subsequent clinical events, and TNF-a remained significant in multivariate analysis (HR = 4.16, p = 0.001). In young HIV-infected women in Botswana inflammatory marker concentrations did not differ significantly between women who breast- vs. formula-fed. However, postpartum TNF-a level was predictive of subsequent adverse clinical event.
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Funding: This study was funded by National Institutes of Health National Institute of Child Health and Human Development Grants: R01 HD37793 and R01
HD44391. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Pregnancy and breastfeeding are associated with modulation of
the immune system toward immune regulation and reduced Th1
responses [1,2]. Hormonal changes during pregnancy, which
persist in part during breastfeeding, are one cause of this immune
shift [3]; breastfeeding and the hormone prolactin have been
shown to be associated with B-cell production and reduced
inflammatory responses [4,5]. Such data support a hypothesis that
breastfeeding could, at least transiently, influence HIV-1 disease
progression through regulation of the immune response. Some,
but not all [6,7,8], studies suggest that breastfeeding is associated
with more rapid CD4 count decline or adverse health outcomes
among HIV-infected women [9]. In one trial conducted in Kenya
among HIV-infected women without access to antiretroviral
treatment (ART), women randomized to breastfeeding had a
higher mortality at two-years postpartum compared with those
randomized to formula-feeding (10.5% vs. 3.8%, respectively)
[10]. Similarly, a trend toward more rapid progression to AIDS or
death was observed at six months postpartum in women
randomized to breastfeeding in the Botswana Mashi trial, possibly
as a result of higher maternal inflammation as suggested by CRP
level, despite similar micronutrient level [11]. The cause of this
potentially higher rate of HIV disease progression and adverse
clinical outcomes associated with breastfeeding among
HIVinfected women is unknown, and to our knowledge there are no
published data on the association between inflammation an (...truncated)