title: Effects of Well-Controlled HIV Infection on Complement Activation and Function.
abstract: Uncontrolled HIV infection is known to activate the complement system, leading to an increase in chronic inflammation. Whether or not this activation of complement persists and contributes to chronic inflammation in subjects with HIV infection that is well controlled through use of antiretroviral therapy has not been studied.
  
  
  
  We conducted an observational, cross-sectional study using sera from 305 adults with well-controlled HIV infection and 30 healthy controls. Sera was tested for markers of complement activation (C3a and C5a levels), complement function (CH50 assay), and immunoglobulin levels (IgG1-IgG4) as IgG can activate complement. We evaluated the association of well-controlled HIV infection with C3a, C5a, CH50, IgG1-IgG4, and total IgG levels using both univariate and multivariate analyses, controlling for factors such as age, sex, race, comorbidities (including hepatitis C coinfection), smoking status, and statin use.
  
  
  
  Well-controlled HIV infection was associated with a 54% increase in complement activation as measured by C3a levels compared with healthy controls (P < 0.0001). Hepatitis C coinfection was associated with a further 52% increase in complement activation, as measured by C3a levels, over HIV alone (P = 0.003).
  
  
  
  These results suggest that complement activation may contribute to a proinflammatory state even in well-controlled HIV infection. Furthermore, hepatitis C virus coinfection may be even more proinflammatory, in complement activation, compared with HIV infection alone.
authors.affiliation: *Division of Infectious Diseases, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA; †Center for Health Analytics and Discovery, Office of Research, Eastern Virginia Medical School, Norfolk, VA; ‡Department of Pediatrics, Eastern Virginia Medical School, Norfolk, VA; §Children's Specialty Group, Norfolk, VA; and ‖Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA.
authors.forename: Alexandria
authors.initials: A
authors.lastname: E-B Rossheim
authors.forename: Tina D
authors.initials: TD
authors.lastname: Cunningham
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Hair
authors.forename: Tushar
authors.initials: T
authors.lastname: Shah
authors.forename: Kenji M
authors.initials: KM
authors.lastname: Cunnion
authors.forename: Stephanie B
authors.initials: SB
authors.lastname: Troy
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003167:Complement Activation; D003165:Complement System Proteins / Q000378:metabolism / Q000502:physiology*; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged
chemical_list: D007074:Immunoglobulin G; D003165:Complement System Proteins