title: Elevated Hepcidin Is Part of a Complex Relation That Links Mortality with Iron Homeostasis and Anemia in Men and Women with HIV Infection.
abstract: BACKGROUND
  Early and chronic inflammation is a hallmark of HIV 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 [α1-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/μL (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 dose-dependent 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.
authors.affiliation: Department of Nutritional Sciences, Cornell University, Ithaca, NY;
authors.forename: Peter A
authors.initials: PA
authors.lastname: Minchella
authors.affiliation: Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom;
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Armitage
authors.affiliation: Medical Research Council Unit (UK), Fajara, The Gambia;
authors.forename: Bakary
authors.initials: B
authors.lastname: Darboe
authors.affiliation: Medical Research Council Unit (UK), Fajara, The Gambia;
authors.forename: Momodou W
authors.initials: MW
authors.lastname: Jallow
authors.affiliation: Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom;
authors.forename: Hal
authors.initials: H
authors.lastname: Drakesmith
authors.affiliation: Medical Research Council Unit (UK), Fajara, The Gambia;
authors.forename: Assan
authors.initials: A
authors.lastname: Jaye
authors.affiliation: International Nutrition Group, Department of Nutrition and Public Health Intervention Unit, London School of Hygiene and Tropical Medicine, London, United Kingdom; and.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Prentice
authors.affiliation: Department of Nutritional Sciences, Cornell University, Ithaca, NY; jmm585@cornell.edu.
authors.forename: Joann M
authors.initials: JM
authors.lastname: McDermid
mesh_terms: D000328:Adult; D018798:Anemia, Iron-Deficiency / Q000097:blood* / Q000150:complications / Q000401:mortality*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D018791:CD4 Lymphocyte Count; D005260:Female; D005293:Ferritins / Q000097:blood; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000401:mortality*; D006454:Hemoglobins / Q000378:metabolism; D064451:Hepcidins / Q000097:blood*; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications; D008297:Male; D015995:Prevalence; D025341:Principal Component Analysis; D016016:Proportional Hazards Models; D011990:Receptors, Transferrin / Q000097:blood; D012189:Retrospective Studies; D014168:Transferrin / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D064451:Hepcidins; D011990:Receptors, Transferrin; D014168:Transferrin; D005293:Ferritins
keywords: Africa; HIV-2; cohort; ferritin; hemoglobin; inflammation; nutrition; survival; transferrin; transferrin receptor