title: Reductions in Plasma Cystatin C After Initiation of Antiretroviral Therapy Are Associated With Reductions in Inflammation: ACTG A5224s.
abstract: BACKGROUND
  Among patients with HIV infection, changes in the kidney filtration marker cystatin C after initiation of antiretroviral therapy (ART) may be related to changes in body composition or biomarkers of inflammation.
  
  
  METHODS
  ACTG A5224s was a substudy of A5202, which randomly assigned ART-naive HIV-infected subjects to blinded abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or ritonavir-boosted atazanavir. This analysis explored changes in cystatin C from 0 to 96 weeks.
  
  
  RESULTS
  Of the 269 subjects, 85% were male and 66% white non-Hispanics; baseline mean CD4 count was 236 cells per cubic millimeter and cystatin C was 0.89 mg/L. Cystatin C decreased significantly within each arm; however, ritonavir-boosted atazanavir attenuated the beneficial effects of ART on cystatin C compared to EFV. Compared to ABC/3TC, TDF/FTC led to a marginally significant attenuation for percent change analyses only. Higher baseline body mass index and HIV RNA were associated with larger reductions in cystatin C in multivariable models. At baseline, cystatin C was positively correlated with high-sensitivity C-reactive protein (Spearman r = 0.25), interleukin 6 (r = 0.34), soluble intercellular adhesion molecule (r = 0.36), soluble vascular cell adhesion molecule (r = 0.54), tumor necrosis factor α (r = 0.57), and soluble TNF-α receptor I (r = 0.70, all P < 0.001). Reductions in cystatin C from 0 to 96 weeks correlated with reductions in all inflammatory biomarkers (r = 0.39-0.58, P < 0.001) except for high-sensitivity C-reactive protein (r = 0.01, P = 0.89) and IL-6 (r = 0.08, P = 0.24).
  
  
  CONCLUSIONS
  The beneficial effect of ART on cystatin C concentrations is attenuated by boosted ATV when compared to EFV. Reductions in cystatin C after ART are associated with reductions in systemic inflammation.
authors.affiliation: *Division of Cardiovascular Medicine, Case Western Reserve University School of Medicine, Cleveland, OH; †Division of Infectious Diseases and Department of Pediatrics University Hospitals Case Medical Center, Cleveland, OH; ‡Department of Biostatistics, Harvard School of Public Health, Boston, MA; §Division of Infectious Diseases, Harvard Medical School, Boston, MA; ‖Department of Biostatistics, Brigham and Women's Hospital, Boston, MA; ¶Division of Infectious Diseases, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA; and #Division of Infectious Diseases, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Chris T
authors.initials: CT
authors.lastname: Longenecker
authors.forename: Douglas
authors.initials: D
authors.lastname: Kitch
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sax
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.forename: Camlin
authors.initials: C
authors.lastname: Tierney
authors.forename: Samir K
authors.initials: SK
authors.lastname: Gupta
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
mesh_terms: D000293:Adolescent; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D055316:Cystatin C / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D055316:Cystatin C