Reductions in Plasma Cystatin C After Initiation of Antiretroviral Therapy Are Associated With Reductions in Inflammation: ACTG A5224s

Samir K Gupta; Chris T Longenecker; Douglas Kitch; Paul E Sax; Eric S Daar; Camlin Tierney; Grace A McComsey; AIDS Clinical Trials Group Study A5224s Team

doi:10.1097/QAI.0000000000000557

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Reductions in Plasma Cystatin C After Initiation of Antiretroviral Therapy Are Associated With Reductions in Inflammation: ACTG A5224s

Journal article

Open access

Peer reviewed

Reductions in Plasma Cystatin C After Initiation of Antiretroviral Therapy Are Associated With Reductions in Inflammation: ACTG A5224s

Samir K Gupta, Chris T Longenecker, Douglas Kitch, Paul E Sax, Eric S Daar, Camlin Tierney, Grace A McComsey and AIDS Clinical Trials Group Study A5224s Team

Journal of acquired immune deficiency syndromes (1999), Vol.69(2), pp.168-177

06/01/2015

DOI: 10.1097/QAI.0000000000000557

PMCID: PMC4445470

PMID: 26009829

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Abstract

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. 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. 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). 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.

Inflammation - pathology

Anti-Retroviral Agents - therapeutic use

Cystatin C - blood

Humans

Middle Aged

Male

Treatment Outcome

Young Adult

HIV Infections - pathology

Plasma - chemistry

Adolescent

Adult

Female

HIV Infections - drug therapy

Antiretroviral Therapy, Highly Active - methods

Details

Title: Subtitle: Reductions in Plasma Cystatin C After Initiation of Antiretroviral Therapy Are Associated With Reductions in Inflammation: ACTG A5224s
Creators: Samir K Gupta
Chris T Longenecker - 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
Douglas Kitch
Paul E Sax
Eric S Daar
Camlin Tierney
Grace A McComsey
AIDS Clinical Trials Group Study A5224s Team
Contributors: Jack T Stapleton (Contributor) - University of Iowa, Internal Medicine
Resource Type: Journal article
Publication Details: Journal of acquired immune deficiency syndromes (1999), Vol.69(2), pp.168-177
DOI: 10.1097/QAI.0000000000000557
PMID: 26009829
PMCID: PMC4445470
NLM abbreviation: J Acquir Immune Defic Syndr
ISSN: 1525-4135
eISSN: 1944-7884
Grant note: AI69432 / NIAID NIH HHS U01 AI069452 / NIAID NIH HHS U01 AI027661 / NIAID NIH HHS U01AI069511-02 / NIAID NIH HHS P30-AI0450008-11 / NIAID NIH HHS U01 AI038855 / NIAID NIH HHS UM1 AI069474 / NIAID NIH HHS U01 AI069471 / NIAID NIH HHS R01 AI065348 / NIAID NIH HHS U01 AI046339 / NIAID NIH HHS AI069474 / NIAID NIH HHS AI 27661 / NIAID NIH HHS UL1 TR000457 / NCATS NIH HHS UL1 RR 024160 / NCRR NIH HHS P30 AI050410(-11) / NIAID NIH HHS U01 AI069474 / NIAID NIH HHS P30 AI045008 / NIAID NIH HHS U01 AI069511 / NIAID NIH HHS UM1 AI069415 / NIAID NIH HHS UL 1RR 025747 / NCRR NIH HHS AI46339-01 / NIAID NIH HHS M01 RR00750 / NCRR NIH HHS 5U01 AI069 484-02 / NIAID NIH HHS U01 AI069532 / NIAID NIH HHS U01 AI069495 / NIAID NIH HHS UM1 AI069434 / NIAID NIH HHS U01 AI069472-04 / NIAID NIH HHS 5U01AI069494 / NIAID NIH HHS AI69450 / NIAID NIH HHS U01 AI034853 / NIAID NIH HHS U01 AI069513 / NIAID NIH HHS U01 AI027658 / NIAID NIH HHS AI069434 / NIAID NIH HHS 5-U01 AI069423-03 / NIAID NIH HHS AI0694241 / NIAID NIH HHS UM1 AI069501 / NIAID NIH HHS UL1TR000124 / NCATS NIH HHS UL1 RR025780 / NCRR NIH HHS 5 U0I AI069415-03 / NIAID NIH HHS AI38855 / NIAID NIH HHS M01 RR000750 / NCRR NIH HHS U01 AI069450 / NIAID NIH HHS UL1 TR001082 / NCATS NIH HHS UM1 AI069511 / NIAID NIH HHS AI069472 / NIAID NIH HHS UL1 RR024992 / NCRR NIH HHS AI27658 / NIAID NIH HHS 1 U01 AI069494-01 / NIAID NIH HHS AI065348 / NIAID NIH HHS U01 AI068634 / NIAID NIH HHS UL1 TR000448 / NCATS NIH HHS U01 AI027668 / NIAID NIH HHS AI069424 / NIAID NIH HHS P30AL050409 / PHS HHS UM1 AI069534 / NIAID NIH HHS U01 AI68634 / NIAID NIH HHS U01 AI069494 / NIAID NIH HHS UL1 RR025005 / NCRR NIH HHS UL1 RR024996 / NCRR NIH HHS AI069532 / NIAID NIH HHS UO1-AI069467-04 / NIAID NIH HHS U01 AI069432 / NIAID NIH HHS MO1 RR 00095 / NCRR NIH HHS U01 AI069467 / NIAID NIH HHS U01 AI068636 / NIAID NIH HHS U01 AI027665 / NIAID NIH HHS AI069513 / NIAID NIH HHS 1U01AI069424-01 / NIAID NIH HHS P30 AI050410 / NIAID NIH HHS UM1 AI069472 / NIAID NIH HHS U01AI069452 / NIAID NIH HHS AI34853 / NIAID NIH HHS U01 AI069501 / NIAID NIH HHS UM1 AI069450 / NIAID NIH HHS UL1 RR024979 / NCRR NIH HHS RR025780 / NCRR NIH HHS UM1 AI069424 / NIAID NIH HHS M01 RR000095 / NCRR NIH HHS UM1 AI068634 / NIAID NIH HHS U01 AI069419 / NIAID NIH HHS UL1 RR025014 / NCRR NIH HHS UM1 AI069532 / NIAID NIH HHS UL1 RR024160 / NCRR NIH HHS U01 AI046376 / NIAID NIH HHS U01 AI069423 / NIAID NIH HHS UO1AL69418-01 / PHS HHS AI27665 / NIAID NIH HHS UM1 AI068636 / NIAID NIH HHS K23 HL123341 / NHLBI NIH HHS N01 AI72626 / NIAID NIH HHS AI32782 / NIAID NIH HHS 5U01AI025859 / NIAID NIH HHS U01 AI069415 / NIAID NIH HHS AI69501 / NIAID NIH HHS UL1 TR000124 / NCATS NIH HHS UM1 AI069513 / NIAID NIH HHS AI0450008 / NIAID NIH HHS U01 AI069472 / NIAID NIH HHS UL1 TR002319 / NCATS NIH HHS U01 AI025859 / NIAID NIH HHS U01 AI069434 / NIAID NIH HHS UL1RR024979 / NCRR NIH HHS U01 AI032782 / NIAID NIH HHS UM1 AI069432 / NIAID NIH HHS UOI AI 069472 / NIAID NIH HHS U01 AI069424 / NIAID NIH HHS
Language: English
Date published: 06/01/2015
Academic Unit: Microbiology and Immunology; Infectious Diseases; Internal Medicine
Record Identifier: 9984094358102771

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