title: Elevated levels of asymmetric dimethylarginine are associated with lower CD4+ count and higher viral load in HIV-infected individuals.
abstract: OBJECTIVE
  To compare asymmetric dimethylarginine (ADMA) among HIV-infected and uninfected individuals and to evaluate predictors of ADMA in HIV infection.
  
  
  BACKGROUND
  HIV-infected individuals have high rates of atherosclerosis. Endothelial dysfunction is central to atherogenesis and is one possible mechanism underlying this increased cardiovascular risk. ADMA is an endogenous inhibitor of endothelial nitric oxide synthase. Among uninfected individuals, higher ADMA levels predict cardiovascular events and mortality. The association between HIV infection, HIV-related factors, and ADMA has not been well described.
  
  
  METHODS
  We compared ADMA in 248 HIV-infected individuals and 50 uninfected controls. We performed multivariable analysis using traditional cardiovascular and HIV-specific factors as covariates to identify factors associated with ADMA.
  
  
  RESULTS
  HIV-infected men were older, less often Caucasian, more hypertensive, and had lower HDL than uninfected men. The median duration of HIV infection was 13 years, median CD4+ count was 592 cells/μL, 76% had an undetectable viral load, and 76% were on antiretroviral therapy. ADMA levels were modestly higher in HIV-infected individuals than controls [median (IQR): 0.46 μM (0.41-0.52) vs. 0.44 μM (0.38-0.46), p = 0.019], but the association lost statistical significance after controlling for cardiovascular risk factors (+0.028 μM, p = 0.054). Lower CD4+ count and both detectable and higher viral load were independently associated with increased ADMA.
  
  
  CONCLUSIONS
  ADMA levels were modestly elevated in the setting of HIV infection. Notably, a greater HIV-associated inflammatory burden, as evidenced by lower CD4+ counts and higher viral loads, was associated with increased ADMA levels. Our findings suggest that HIV infection impairs endothelial function and predisposes to atherosclerosis through chronic inflammation and subsequent accumulation of ADMA.
authors.affiliation: Department of Medicine, University of California, San Francisco, USA.
authors.forename: Rushi V
authors.initials: RV
authors.lastname: Parikh
authors.forename: Rebecca
authors.initials: R
authors.lastname: Scherzer
authors.forename: Carl
authors.initials: C
authors.lastname: Grunfeld
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Nitta
authors.forename: Anna
authors.initials: A
authors.lastname: Leone
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Peter
authors.initials: P
authors.lastname: Ganz
authors.forename: Priscilla Y
authors.initials: PY
authors.lastname: Hsue
mesh_terms: D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000821:virology*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000453:epidemiology / Q000276:immunology*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009569:Nitric Oxide / Q000097:blood; D011237:Predictive Value of Tests; D012307:Risk Factors; D019562:Viral Load / Q000276:immunology*
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine