title: The use of humoral responses as a marker of CMV burden in HIV patients on ART requires consideration of T-cell recovery and persistent B-cell activation.
abstract: OBJECTIVE
  Elevated humoral responses to cytomegalovirus (CMV) associate with increased risk of cardiovascular disease (CVD) in HIV patients on antiretroviral therapy (ART). To better understand the persistence of CMV humoral responses in relation to CVD, we determined trends in CMV antibody levels over the first 10 years on ART.
  
  
  METHODS
  We describe longitudinal analyses of plasma from 13 HIV patients commencing ART with <210 CD4 T-cells/µL and 27 controls. Antibodies reactive with CMV (fibroblast lysate, gB and IE-1 antigens), EBV-VCA, and HIVgp41 were quantitated. B-cell activation was assessed via total IgG and sBAFF. Inflammation was assessed via sTNF-RI and sCD14.
  
  
  RESULTS
  Amongst CMV seropositive HIV patients, levels of antibody reactive with CMV (P = 0.03) and EBV-VCA (P = 0.02) peaked after 1 year on ART. Levels of total IgG, sCD14, and sTNF-RI declined to approximate those in controls after 10 years, but sBAFF (P = 0.0002), EBV-VCA (P = 0.001), and CMV (P = 0.0004) antibodies remained elevated. A strong correlation between sBAFF and CMVgB antibody was seen at 10 years (R = 0.93, P = 0.0009) and verified in a second cohort.
  
  
  CONCLUSIONS
  CMV antibody titres peak on ART and remain high. A correlation between CMV antibody and sBAFF suggests a role for HIV-induced B-cell pathology that may affect its use as a marker of CMV burden.
authors.affiliation: School of Pathology and Laboratory Medicine, University of WA, Nedlands, WA 6009, Australia.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Brunt
authors.affiliation: Microbiology and Infectious Diseases, Royal Perth Hospital, Perth, WA 6000, Australia.
authors.forename: Silvia
authors.identifier: 0000-0001-5405-9735
authors.initials: S
authors.lastname: Lee
authors.affiliation: School of Pathology and Laboratory Medicine, University of WA, Nedlands, WA 6009, Australia ; Clinical Immunology and Immunogenetics, Royal Perth Hospital, Perth, WA 6000, Australia.
authors.forename: Lloyd
authors.initials: L
authors.lastname: D'Orsogna
authors.affiliation: School of Pathology and Laboratory Medicine, University of WA, Nedlands, WA 6009, Australia ; Immunology & Immunopathology, PathWest Laboratory Medicine, Nedlands, WA 6009, Australia.
authors.forename: Christine
authors.identifier: 0000-0002-6372-1513
authors.initials: C
authors.lastname: Bundell
authors.affiliation: Medicine and Pharmacology, University of WA, Nedlands, WA 6009, Australia.
authors.forename: Sally
authors.identifier: 0000-0002-8499-4537
authors.initials: S
authors.lastname: Burrows
authors.affiliation: School of Pathology and Laboratory Medicine, University of WA, Nedlands, WA 6009, Australia ; Clinical Immunology and Immunogenetics, Royal Perth Hospital, Perth, WA 6000, Australia.
authors.forename: Patricia
authors.identifier: 0000-0002-6312-2203
authors.initials: P
authors.lastname: Price
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000097:blood; D053264:B-Cell Activating Factor / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D060085:Coinfection / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D000914:Antibodies, Viral; D053264:B-Cell Activating Factor; D015415:Biomarkers; C505719:TNFSF13B protein, human