title: Comparison of cardiovascular disease risk markers in HIV-infected patients receiving abacavir and tenofovir: the nucleoside inflammation, coagulation and endothelial function (NICE) study.
abstract: BACKGROUND
  The association between abacavir (ABC) and cardiovascular disease (CVD) risk in HIV-infected individuals is unclear. Putative mechanisms for an effect of ABC on CVD risk including endothelial dysfunction have been proposed; however, a biological mechanism has not been established.
  
  
  METHODS
  This was a cross-sectional study of HIV-infected subjects with HIV RNA levels <400 copies/ml, who were randomly assigned to ABC or tenofovir (TDF) as initial therapy during a prior clinical trial. A small cohort of subjects on zidovudine (AZT; not randomly assigned) were studied to explore long-term exposure to this agent. All underwent brachial artery ultrasound for flow-mediated dilation (FMD), and D-dimer, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and fasting lipids were measured. Between-arm differences were evaluated by multivariable linear or logistic regression modelling.
  
  
  RESULTS
  There were 148 subjects (46 on ABC, 72 on TDF and 30 on AZT). Demographic characteristics were balanced across the groups except, as expected, AZT-treated participants were older, had higher CD4(+) T-cell counts, and longer antiretroviral therapy duration. After adjusting for age, brachial artery diameter, and treatment duration, FMD was similar in those on ABC (3.9%) and TDF (5.4%; P=0.181). FMD was higher in those on AZT (6.1%; P<0.005). Levels of IL-6, hsCRP and detectable D-dimer were similar between groups.
  
  
  CONCLUSIONS
  Among individuals assigned to ABC or TDF in randomized clinical trials there were no significant differences in FMD or markers of inflammation and coagulation. Whether ABC contributes to risk of CVD remains unclear, but our results suggest that endothelial dysfunction, heightened inflammation, and altered coagulation are unlikely to be mechanisms by which the drug could increase CVD risk above that seen with TDF.
authors.affiliation: Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC, USA. wohl@med.unc.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Wohl
authors.forename: Gretchen
authors.initials: G
authors.lastname: Arnoczy
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Fichtenbaum
authors.forename: Thomas
authors.initials: T
authors.lastname: Campbell
authors.forename: Babafemi
authors.initials: B
authors.lastname: Taiwo
authors.forename: Charles
authors.initials: C
authors.lastname: Hicks
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
authors.forename: Susan
authors.initials: S
authors.lastname: Koletar
authors.forename: Paul
authors.initials: P
authors.lastname: Sax
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.forename: Belinda
authors.initials: B
authors.lastname: Ha
authors.forename: Kelly
authors.initials: K
authors.lastname: Massengale
authors.forename: Kendall
authors.initials: K
authors.lastname: Walsh
authors.forename: James H
authors.initials: JH
authors.lastname: Stein
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000378:metabolism*; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D000068698:Tenofovir; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000099227:Abacavir
chemical_list: D000225:Adenine; D019380:Anti-HIV Agents; D015415:Biomarkers; D015224:Dideoxynucleosides; D063065:Organophosphonates; D000068698:Tenofovir; D015215:Zidovudine; D000099227:Abacavir