title: Immune activation markers in peripartum women in Botswana: association with feeding strategy and maternal morbidity.
abstract: 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 HIV-infected women, though certain inflammatory markers are associated with adverse health outcomes among HIV-infected persons. We measured hsCRP, D-dimer, IFN-γ, IL-6, IL-10 and TNF-α 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-γ 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-α, D-dimer, and IFN-γ concentrations at six months postpartum were significant predictors of subsequent clinical events, and TNF-α 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-α level was predictive of subsequent adverse clinical event.
authors.affiliation: Harvard AIDS Initiative, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America; Botswana-Harvard AIDS Institute, Gaborone, Botswana.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Russell
authors.affiliation: Botswana-Harvard AIDS Institute, Gaborone, Botswana.
authors.forename: Terence
authors.initials: T
authors.lastname: Mohammed
authors.affiliation: Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Laura
authors.initials: L
authors.lastname: Smeaton
authors.affiliation: Botswana-Harvard AIDS Institute, Gaborone, Botswana.
authors.forename: Baitshepi
authors.initials: B
authors.lastname: Jorowe
authors.affiliation: Harvard AIDS Initiative, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America; Botswana-Harvard AIDS Institute, Gaborone, Botswana.
authors.forename: Iain J
authors.initials: IJ
authors.lastname: MacLeod
authors.affiliation: David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Risa M
authors.initials: RM
authors.lastname: Hoffman
authors.affiliation: David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Judith S
authors.initials: JS
authors.lastname: Currier
authors.affiliation: Botswana-Harvard AIDS Institute, Gaborone, Botswana.
authors.forename: Sikhulile
authors.initials: S
authors.lastname: Moyo
authors.affiliation: Harvard AIDS Initiative, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America; Botswana-Harvard AIDS Institute, Gaborone, Botswana.
authors.forename: Max
authors.initials: M
authors.lastname: Essex
authors.affiliation: Harvard AIDS Initiative, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America; Botswana-Harvard AIDS Institute, Gaborone, Botswana; Department of Medicine, Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Shahin
authors.initials: S
authors.lastname: Lockman
mesh_terms: D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D001902:Botswana; D001942:Breast Feeding; D018791:CD4 Lymphocyte Count; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D015658:HIV Infections / Q000150:complications / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D041943:Infant Formula; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D015999:Multivariate Analysis; D058725:Peripartum Period; D049590:Postpartum Period; D011247:Pregnancy; D011379:Prognosis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C036309:fibrin fragment D; D016753:Interleukin-10; D007371:Interferon-gamma