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 Gupta, Grace A. McComsey

Research output: Contribution to journalArticle

4 Citations (Scopus)

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

Fingerprint

Cystatins
Cystatin C
efavirenz
Inflammation
Therapeutics
Ritonavir
Lamivudine
Tenofovir
C-Reactive Protein
Interleukin-6
Biomarkers
HIV
Vascular Cell Adhesion Molecule-1
Tumor Necrosis Factor Receptors
Cell Adhesion Molecules
CD4 Lymphocyte Count
Body Composition
HIV Infections
Body Mass Index
Tumor Necrosis Factor-alpha

Keywords

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

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Reductions in plasma cystatin c after initiation of antiretroviral therapy are associated with reductions in inflammation : ACTG A5224s. / Longenecker, Chris T.; Kitch, Douglas; Sax, Paul E.; Daar, Eric S.; Tierney, Camlin; Gupta, Samir; McComsey, Grace A.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 69, No. 2, 01.06.2015, p. 168-177.

Research output: Contribution to journalArticle

Longenecker, Chris T. ; Kitch, Douglas ; Sax, Paul E. ; Daar, Eric S. ; Tierney, Camlin ; Gupta, Samir ; McComsey, Grace A. / Reductions in plasma cystatin c after initiation of antiretroviral therapy are associated with reductions in inflammation : ACTG A5224s. In: Journal of Acquired Immune Deficiency Syndromes. 2015 ; Vol. 69, No. 2. pp. 168-177.
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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.",
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AU - Longenecker, Chris T.

AU - Kitch, Douglas

AU - Sax, Paul E.

AU - Daar, Eric S.

AU - Tierney, Camlin

AU - Gupta, Samir

AU - McComsey, Grace A.

PY - 2015/6/1

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N2 - 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.

AB - 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.

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KW - cystatin C

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