title: Association of Arterial and Lymph Node Inflammation With Distinct Inflammatory Pathways in Human Immunodeficiency Virus Infection.
abstract: Human immunodeficiency virus (HIV) infection is associated with a high risk of cardiovascular disease and increased arterial inflammation. In HIV, inflammation is also increased within lymph nodes (LNs), tissues known to harbor the virus even among treated and suppressed individuals.
  
  
  
  To test the hypothesis that arterial inflammation is linked to HIV disease activity and to inflammation within HIV-infected tissues (LNs).
  
  
  
  For this case-control study, participants were recruited from the SCOPE (Observational Study of the Consequences of the Protease Inhibitor Era) cohort, a clinic-based cohort of individuals receiving care at San Francisco General Hospital and the San Francisco Veteran's Affairs Medical Center. Arterial and LN inflammation were measured using 18F-fluorodeoxyglucose positron emission tomography. Detailed immunophenotyping was performed, along with measurement of viral activity/persistence and of circulating inflammatory biomarkers.
  
  
  
  Arterial and LN inflammation.
  
  
  
  A total of 74 men were studied (45 HIV-infected men with a median age of 53 years [interquartile range, 49-59 years] and 29 uninfected male controls with a median age of 52 years [interquartile range, 46-56 years]). Lymph node inflammation was higher in HIV-infected individuals and correlated with markers of viral disease activity (viral load, CD8+ T cells, and CD4/CD8 ratio) and CD4+ T-cell activation. Uninfected controls had the lowest LN activity (mean [SD] maximum axillary LN standardized uptake value, 1.53 [0.56]), the elite controller and ART-suppressed groups had intermediate levels of LN (mean [SD] maximum axillary LN standardized uptake value, 2.12 [0.87] and 2.32 [1.79], respectively), and the noncontrollers had the highest activity (mean [SD] maximum axillary LN standardized uptake value, 8.82 [3.08]). Arterial inflammation was modestly increased in HIV-infected individuals and was positively correlated with circulating inflammatory biomarkers (high-sensitivity C-reactive protein and IL-6) and activated monocytes (CD14dimCD16+; nonclassical) but not with markers of HIV. While LN and arterial inflammation were increased in HIV, inflammatory activity in these tissues was not related (r = 0.09, P = .56).
  
  
  
  While LNs and, to a lesser degree, the arterial wall are inflamed in HIV, inflammation in these tissues is not closely linked. Namely, measures of HIV disease activity are strongly associated with LN inflammation but not with arterial inflammation. These data suggest that LN and arterial inflammation do not share underlying pathways of immune activation and also that therapeutic interventions that reduce viral disease activity may not predictably reduce arterial inflammation in HIV or its downstream consequence (ie, cardiovascular disease).
authors.affiliation: Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Tawakol
authors.affiliation: Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Amorina
authors.initials: A
authors.lastname: Ishai
authors.affiliation: Division of Cardiology, San Francisco General Hospital, University of California, San Francisco.
authors.forename: Danny
authors.initials: D
authors.lastname: Li
authors.affiliation: Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Richard A P
authors.initials: RA
authors.lastname: Takx
authors.affiliation: Division of Cardiology, San Francisco General Hospital, University of California, San Francisco.
authors.forename: Sophia
authors.initials: S
authors.lastname: Hur
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Kaiser
authors.affiliation: Division of Radiology, University of California, San Francisco.
authors.forename: Miguel
authors.initials: M
authors.lastname: Pampaloni
authors.affiliation: Leidos Biomedical Research Inc, Frederick, Maryland.
authors.forename: Adam
authors.initials: A
authors.lastname: Rupert
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Denise
authors.initials: D
authors.lastname: Hsu
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.affiliation: Centre de Recherche du CHUM, Department of Microbiology, Infectiology, and Immunology, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Rémi
authors.initials: R
authors.lastname: Fromentin
authors.affiliation: Centre de Recherche du CHUM, Department of Microbiology, Infectiology, and Immunology, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chomont
authors.affiliation: Division of Cardiology, San Francisco General Hospital, University of California, San Francisco.
authors.forename: Peter
authors.initials: P
authors.lastname: Ganz
authors.affiliation: Positive Health Program at San Francisco General Hospital, University of California, San Francisco.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.affiliation: Division of Cardiology, San Francisco General Hospital, University of California, San Francisco.
authors.forename: Priscilla Y
authors.initials: PY
authors.lastname: Hsue
mesh_terms: D001167:Arteritis / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D018791:CD4 Lymphocyte Count; D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D004279:DNA, Viral / Q000032:analysis*; D006678:HIV / Q000235:genetics*; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D006801:Humans; D015994:Incidence; D008198:Lymph Nodes / Q000000981:diagnostic imaging*; D008199:Lymphadenitis / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019562:Viral Load
chemical_list: D004279:DNA, Viral