title: Markers of inflammation and activation of coagulation are associated with anaemia in antiretroviral-treated HIV disease.
abstract: OBJECTIVE
  The objective of this study is to determine the relationship between inflammatory interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP)] and coagulation (D-dimer) biomarkers and the presence and type of anaemia among HIV-positive individuals.
  
  
  METHODS
  A cross-sectional study.
  
  
  METHODS
  Combination antiretroviral therapy (cART)-treated adults participating in an international HIV trial with haemoglobin and mean corpuscular volume (MCV) measurements at entry were categorized by presence of anaemia (haemoglobin ≤14 g/dl in men and ≤12 g/dl in women) and, for those with anaemia, by type [microcytic (MCV < 80 fl), normocytic (80-100 fl), macrocytic (>100 fl)]. We analysed the association between inflammation (IL-6 and hsCRP) and coagulation (D-dimer) and haemoglobin, controlling for demographics (age, race and sex), BMI, HIV plasma RNA levels, CD4⁺ T-cell counts (nadir and baseline), Karnofsky score, previous AIDS diagnosis, hepatitis B/C coinfection and use of zidovudine.
  
  
  RESULTS
  Among 1410 participants, 313 (22.2%) had anaemia. Of these, 4.1, 27.2 and 68.7% had microcytic, normocytic and macrocytic anaemia, respectively. When compared with participants with normal haemoglobin values, those with anaemia were more likely to be older, black, male and on zidovudine. They also had lower baseline CD4⁺ T-cell counts and lower Karnofsky scores. Adjusted relative odds of anaemia per two-fold higher biomarker levels were 1.22 (P = 0.007) for IL-6, 0.99 for hsCRP (P = 0.86) and 1.35 (P < 0.001) for D-dimer. Similar associations were seen in those with normal and high MCV values.
  
  
  CONCLUSIONS
  Persistent inflammation and hypercoagulation appear to be associated with anaemia. Routine measurements of haemoglobin might provide insights into the inflammatory state of treated HIV infection.
authors.affiliation: aCentre for Health and Infectious Diseases Research (CHIP), Department of Infectious Diseases and Reumathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark bThrombosis & Atherosclerosis Research Institute and McMaster University, Hamilton, Ontario, Canada cDepartment of Biostatistics dDepartment of Medicine, University of Minnesota eHennepin County Medical Center, Minneapolis, Minnesota, USA fINSERM U955 Equipe 16 gVaccine Research Institute (VRI), Université Paris Est Créteil, Faculté de Médecine hService d'Immunologie Clinique, Hôpital Henri Mondor, AP-HP, Créteil, France iNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA jResearch Department of Infection and Population Health, University College London, London, UK kDepartment of Medicine, University of California, San Francisco, California, USA.
authors.forename: Álvaro H
authors.initials: ÁH
authors.lastname: Borges
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Weitz
authors.forename: Gary
authors.initials: G
authors.lastname: Collins
authors.forename: Jason V
authors.initials: JV
authors.lastname: Baker
authors.forename: Yves
authors.initials: Y
authors.lastname: Lévy
authors.forename: Richard T
authors.initials: RT
authors.lastname: Davey
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
authors.forename: James D
authors.initials: JD
authors.lastname: Neaton
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
mesh_terms: D000328:Adult; D000740:Anemia / Q000453:epidemiology* / Q000473:pathology*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D001778:Blood Coagulation Disorders / Q000150:complications* / Q000473:pathology; D002097:C-Reactive Protein / Q000032:analysis; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D010949:Plasma / Q000821:virology; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D005338:Fibrin Fibrinogen Degradation Products; D006454:Hemoglobins; D015850:Interleukin-6; C036309:fibrin fragment D; D002097:C-Reactive Protein