title: Potential cardiovascular disease risk markers among HIV-infected women initiating antiretroviral treatment.
abstract: BACKGROUND
  Inflammation and hemostasis perturbation may be involved in vascular complications of HIV infection. We examined atherogenic biomarkers and subclinical atherosclerosis in HIV-infected adults before and after beginning highly active antiretroviral therapy (HAART).
  
  
  METHODS
  In the Women's Interagency HIV Study, 127 HIV-infected women studied pre and post HAART were matched to HIV-uninfected controls. Six semiannual measurements of soluble CD14, tumor necrosis factor (TNF) alfa, soluble interleukin (IL) 2 receptor, IL-6, IL-10, monocyte chemoattractant protein 1, D-dimer, and fibrinogen were obtained. Carotid artery intima-media thickness was measured by B-mode ultrasound.
  
  
  RESULTS
  Relative to HIV-uninfected controls, HAART-naive HIV-infected women had elevated levels of soluble CD14 (1945 vs 1662 ng/mL, Wilcoxon signed rank P < 0.0001), TNF-α (6.3 vs 3.4 pg/mL, P < 0.0001), soluble IL-2 receptor (1587 vs 949 pg/mL, P < 0.0001), IL-10 (3.3 vs 1.9 pg/mL, P < 0.0001), monocyte chemoattractant protein 1 (190 vs 163 pg/mL, P < 0.0001), and D-dimer (0.43 vs 0.31 μg/mL, P < 0.01). Elevated biomarker levels declined after HAART. Although most biomarkers normalized to HIV-uninfected levels, in women on effective HAART, TNF-α levels remained elevated compared with HIV-uninfected women (+0.8 pg/mL, P = 0.0002). Higher post-HAART levels of soluble IL-2 receptor (P = 0.02), IL-6 (P = 0.05), and D-dimer (P = 0.03) were associated with increased carotid artery intima-media thickness.
  
  
  CONCLUSIONS
  Untreated HIV infection is associated with abnormal hemostasis (eg, D-dimer), proatherogenic (eg, TNF-α), and antiatherogenic (eg, IL-10) inflammatory markers. HAART reduces most inflammatory mediators to HIV-uninfected levels. Increased inflammation and hemostasis are associated with subclinical atherosclerosis in recently treated women. These findings have potential implications for long-term risk of cardiovascular disease in HIV-infected patients, even with effective therapy.
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. Robert.kaplan@einstein.yu.edu
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kaplan
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
authors.forename: Howard N
authors.initials: HN
authors.lastname: Hodis
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gange
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Norris
authors.forename: Mary
authors.initials: M
authors.lastname: Young
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Phyllis C
authors.initials: PC
authors.lastname: Tien
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Xue
authors.forename: Jason
authors.initials: J
authors.lastname: Lazar
authors.forename: Christina M
authors.initials: CM
authors.lastname: Parrinello
authors.forename: Lorie
authors.initials: L
authors.lastname: Benning
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D050197:Atherosclerosis / Q000175:diagnosis / Q000453:epidemiology*; D015415:Biomarkers / Q000097:blood*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology; D016207:Cytokines / Q000097:blood; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D015995:Prevalence; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000473:pathology; D014463:Ultrasonography
chemical_list: D044966:Anti-Retroviral Agents; D015415:Biomarkers; D016207:Cytokines; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D005340:Fibrinogen