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 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 (US)
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 K.; 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 K. ; 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.
@article{c45de50e07ea4909a8114012e8f2c313,
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 (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.",
keywords = "antiretroviral therapy, cystatin C, glomerular filtration rate, inflammation, kidney",
author = "Longenecker, {Chris T.} and Douglas Kitch and Sax, {Paul E.} and Daar, {Eric S.} and Camlin Tierney and Gupta, {Samir K.} and McComsey, {Grace A.}",
year = "2015",
month = "6",
day = "1",
doi = "10.1097/QAI.0000000000000557",
language = "English (US)",
volume = "69",
pages = "168--177",
journal = "Journal of Acquired Immune Deficiency Syndromes",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Reductions in plasma cystatin c after initiation of antiretroviral therapy are associated with reductions in inflammation

T2 - ACTG A5224s

AU - Longenecker, Chris T.

AU - Kitch, Douglas

AU - Sax, Paul E.

AU - Daar, Eric S.

AU - Tierney, Camlin

AU - Gupta, Samir K.

AU - McComsey, Grace A.

PY - 2015/6/1

Y1 - 2015/6/1

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.

KW - antiretroviral therapy

KW - cystatin C

KW - glomerular filtration rate

KW - inflammation

KW - kidney

UR - http://www.scopus.com/inward/record.url?scp=84929877787&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929877787&partnerID=8YFLogxK

U2 - 10.1097/QAI.0000000000000557

DO - 10.1097/QAI.0000000000000557

M3 - Article

C2 - 26009829

AN - SCOPUS:84929877787

VL - 69

SP - 168

EP - 177

JO - Journal of Acquired Immune Deficiency Syndromes

JF - Journal of Acquired Immune Deficiency Syndromes

SN - 1525-4135

IS - 2

ER -