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Minchella P.A.,Cornell University | Armitage A.E.,Weatherall Institute of Molecular Medicine | Darboe B.,Medical Research Council Unit UK | Jallow M.W.,Medical Research Council Unit UK | And 4 more authors.
Journal of Nutrition | Year: 2015

Background: Early and chronic inflammation is a hallmark ofHIV infection, and inflammation is known to increase hepcidin expression. Consequently, hepcidin may be a key determinant of the iron homeostasis and anemia associated with poorer HIV prognoses. Objective: The objective of this study was to understand how hepcidin is related to anemia, iron homeostasis, and inflammation at HIV diagnosis and to investigate associations between hepcidin and all-cause mortality in HIV infection. Methods: In a retrospective cohort, baseline plasma hepcidin was measured by competitive enzyme immunoassay within 3 mo of HIV diagnosis in 196 antiretroviral-naive Gambians. Iron homeostasis [hemoglobin, plasma transferrin, ferritin, iron, soluble transferrin receptor (sTfR)] and inflammation [a1-antichymotrypsin (ACT)] from the same plasma sample were available, as were absolute CD4 cell counts, age, gender, body mass index (BMI), and HIV type. Results: Anemia was common across the spectrum of immunosuppression [CD4 cell counts (prevalence of anemia): >500 cells/mL (68%), 200-500 cells/μL (73%), and <200 cells/μL (89%); P = 0.032] and in men (81%) and women (76%). Increasing hepcidin was associated with iron homeostasis biomarkers (higher ferritin and lower transferrin, hemoglobin, and sTfR), inflammation (higher ACT), and key health indicators (lower CD4 or BMI, advancing age, and male gender; P < 0.001 except for hemoglobin, P = 0.021). Elevated hepcidin was associated with greater all-cause mortality in a dosedependent manner [intermediate vs. lowest tertile: unadjusted HR (95% CI), 1.95 (1.22, 3.10); upper vs. lowest tertile: 3.02 (1.91, 4.78)]. Principal components analysis identified 2 patterns composed of hepcidin-ferritin-transferrin, with or without ACT, and iron-sTfR-hemoglobin that may distinguish inflammation and erythropoiesis iron functions. Conclusions: Elevated hepcidin is independently associated with greater mortality in men and women with HIV infection, and hepcidin is also part of a complex relation linking iron homeostasis, anemia, and HIV. Understanding the mechanisms and role of hepcidin modulation may further guide evidence-based interventions needed to counter detrimental iron homeostasis and anemia in HIV infection. © 2015 American Society for Nutrition.


Minchella P.A.,Cornell University | Armitage A.E.,Weatherall Institute of Molecular Medicine | Darboe B.,Medical Research Council Unit UK | Jallow M.W.,Medical Research Council Unit UK | And 4 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2014

Hepcidin inhibits ferroportin-mediated iron efflux, leading to intracellular macrophage iron retention, possibly favoring Mycobacterium tuberculosis iron acquisition and tuberculosis (TB) pathogenesis. Plasma hepcidin was measured at human immunodeficiency virus (HIV) diagnosis in a retrospective HIV-prevalent, antiretroviral-naïve African cohort to investigate the association with incident pulmonary and/or extrapulmonary TB. One hundred ninety-six participants were followed between 5 August 1992 and 1 June 2002, with 32 incident TB cases identified. Greater hepcidin was associated with significantly increased likelihood of TB after a median time to TB of 6 months. Elucidation of iron-related causal mechanisms and time-sensitive biomarkers that identify individual changes in TB risk are needed. © 2014 The Union.

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