Reductions in plasma cystatin c after initiation of antiretroviral therapy are associated with reductions in inflammation: ACTG A5224s

Chris T. Longenecker, Douglas Kitch, Paul E. Sax, Eric S. Daar, Camlin Tierney, Samir K. Gupta, Grace A. McComsey

Research output: Contribution to journalArticle

5 Scopus citations

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 (r 0.57), and soluble TNF- 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.

Original languageEnglish (US)
Pages (from-to)168-177
Number of pages10
JournalJournal of Acquired Immune Deficiency Syndromes
Volume69
Issue number2
DOIs
StatePublished - Jun 1 2015

Keywords

  • antiretroviral therapy
  • cystatin C
  • glomerular filtration rate
  • inflammation
  • kidney

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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