title: Coinfection with human herpesvirus 8 is associated with persistent inflammation and immune activation in virologically suppressed HIV-infected patients.
abstract: OBJECTIVE
  Infection with co-pathogens is one of the postulated factors contributing to persistent inflammation and non-AIDS events in virologically-suppressed HIV-infected patients. We aimed to investigate the relationship of human herpesvirus-8 (HHV-8), a vasculotropic virus implicated in the pathogenesis of Kaposi's sarcoma, with inflammation and subclinical atherosclerosis in HIV-infected patients.
  
  
  METHODS
  Prospective study including virologically suppressed HIV-infected patients. Several blood biomarkers (highly-sensitive C-reactive protein [hsCRP], tumour necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1, vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, malondialdehyde, plasminogen activator inhibitor [PAI-1], D-dimer, sCD14, sCD163, CD4/CD38/HLA-DR, and CD8/CD38/HLA-DR), serological tests for HHV-8 and the majority of herpesviruses, carotid intima-media thickness, and endothelial function through flow-mediated dilatation of the brachial artery were measured.
  
  
  RESULTS
  A total of 136 patients were included, 34.6% of them infected with HHV-8. HHV-8-infected patients were more frequently co-infected with herpes simplex virus type 2 (HSV-2) (P<0.001), and less frequently with hepatitis C virus (HCV) (P = 0.045), and tended to be older (P = 0.086). HHV-8-infected patients had higher levels of hsCRP (median [interquartile range], 3.63 [1.32-7.54] vs. 2.08 [0.89-4.11] mg/L, P = 0.009), CD4/CD38/HLA-DR (7.67% [4.10-11.86]% vs. 3.86% [2.51-7.42]%, P = 0.035) and CD8/CD38/HLA-DR (8.02% [4.98-14.09]% vs. 5.02% [3.66-6.96]%, P = 0.018). After adjustment for the traditional cardiovascular risk factors, HCV and HSV-2 infection, the associations remained significant: adjusted difference between HHV-8 positive and negative patients (95% confidence interval) for hsCRP, 74.19% (16.65-160.13)%; for CD4/CD38/HLA-DR, 89.65% (14.34-214.87)%; and for CD8/CD38/HLA-DR, 58.41% (12.30-123.22)%. Flow-mediated dilatation and total carotid intima-media thickness were not different according to HHV-8 serostatus.
  
  
  CONCLUSIONS
  In virologically suppressed HIV-infected patients, coinfection with HHV-8 is associated with increased inflammation and immune activation. This might contribute to increase the risk of non-AIDS events, including accelerated atherosclerotic disease.
authors.affiliation: Infectious Diseases Unit, Hospital General Universitario de Elche, Universidad Miguel Hernández, Alicante, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Masiá
authors.affiliation: Infectious Diseases Unit, Hospital General Universitario de Elche, Universidad Miguel Hernández, Alicante, Spain.
authors.forename: Catalina
authors.initials: C
authors.lastname: Robledano
authors.affiliation: Microbiology Service, Hospital Universitario de San Juan, Alicante, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Ortiz de la Tabla
authors.affiliation: Microbiology Service, Hospital Universitario de San Juan, Alicante, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Antequera
authors.affiliation: Department of Public Health, Universidad Miguel Hernández, Alicante, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Lumbreras
authors.affiliation: Department of Public Health, Universidad Miguel Hernández, Alicante, Spain.
authors.forename: Ildefonso
authors.initials: I
authors.lastname: Hernández
authors.affiliation: Infectious Diseases Unit, Hospital General Universitario de Elche, Universidad Miguel Hernández, Alicante, Spain.
authors.forename: Félix
authors.initials: F
authors.lastname: Gutiérrez
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000150:complications* / Q000276:immunology; D059168:Carotid Intima-Media Thickness; D060085:Coinfection / Q000150:complications* / Q000276:immunology; D005260:Female; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000150:complications* / Q000276:immunology; D006566:Herpesviridae Infections / Q000150:complications* / Q000276:immunology; D019288:Herpesvirus 8, Human / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies