title: Increased carotid intima-media thickness associated with antibody responses to varicella-zoster virus and cytomegalovirus in HIV-infected patients.
abstract: OBJECTIVE
  We investigated the relationship of the Herpesviridiae with inflammation and subclinical atherosclerosis in HIV-infected patients.
  
  
  METHODS
  Prospective study including virologically suppressed HIV-infected patients. IgG antibodies against herpesviruses, carotid intima-media thickness (cIMT), endothelial function through flow-mediated dilatation (FMD) of the brachial artery, and blood atherosclerosis biomarkers (hsCRP, TNF-α, IL-6, MCP-1, MDA, sCD14, sCD163, VCAM-1, ICAM-1, D-dimer, and PAI-1) were measured.
  
  
  RESULTS
  136 patients with HIV viral load <200 copies/ml were included. 93.4% patients were infected with herpes simplex virus type-1, 55.9% with herpes simplex virus type-2, 97.1% with varicella-zoster virus, 65.4% with human herpesvirus-6, 91.2% with cytomegalovirus, and 99.3% with Epstein-Barr virus. Previous AIDS diagnosis was associated with higher cytomegalovirus IgG titers (23,000 vs 17,000 AU, P = 0.011) and higher varicella-zoster virus IgG titers (3.19 vs 2.88 AU, P = 0.047), and there was a positive correlation of the Framingham risk score with IgG levels against cytomegalovirus (Spearman's Rho 0.216, P = 0.016) and Herpes simplex virus-2 (Spearman's Rho 0.293, P = 0.001). IgG antibodies against cytomegalovirus correlated in adjusted analysis with the cIMT (P = 0.030). High seropositivity for varicella-zoster virus (OR 2.91, 95% CI 1.05-8.01, P = 0.039), and for cytomegalovirus (OR 3.79, 95% CI 1.20-11.97, P = 0.023) were predictors for the highest quartile of the cIMT in adjusted analyses. PAI-1 levels were independently associated with cytomegalovirus IgG titers (P = 0.041), IL-6 and ICAM-1 levels with varicella-zoster virus IgG (P = 0.046 and P = 0.035 respectively), and hsCRP levels with Herpes simplex virus-2 IgG (P = 0.035).
  
  
  CONCLUSIONS
  In virologically suppressed HIV-infected patients, antibody responses against herpesviruses are associated with subclinical atherosclerosis, and with increased inflammation and coagulation biomarkers.
authors.affiliation: Infectious Diseases Unit, Hospital General Universitario de Elche, Universidad Miguel Hernández, Alicante, Spain. marmasiac@gmail.com
authors.forename: Mar
authors.initials: M
authors.lastname: Masiá
authors.forename: Catalina
authors.initials: C
authors.lastname: Robledano
authors.forename: Victoria
authors.initials: V
authors.lastname: Ortiz de la Tabla
authors.forename: Pedro
authors.initials: P
authors.lastname: Antequera
authors.forename: Natividad
authors.initials: N
authors.lastname: López
authors.forename: Félix
authors.initials: F
authors.lastname: Gutiérrez
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D000917:Antibody Formation; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000276:immunology / Q000821:virology*; D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000276:immunology / Q000821:virology*; D059168:Carotid Intima-Media Thickness; D060085:Coinfection / Q000150:complications / Q000276:immunology / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology / Q000821:virology*; D006562:Herpes Zoster / Q000150:complications / Q000276:immunology* / Q000821:virology; D014645:Herpesvirus 3, Human / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers