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

TitleReductions in Plasma Cystatin C After Initiation of Antiretroviral Therapy Are Associated With Reductions in Inflammation: ACTG A5224s.
Publication TypeJournal Article
Year of Publication2015
AuthorsLongenecker CT, Kitch D, Sax PE, Daar ES, Tierney C, Gupta SK, McComsey GA
Corporate AuthorsAIDS Clinical Trials Group Study A5224s Team
JournalJ Acquir Immune Defic Syndr
Volume69
Issue2
Pagination168-77
Date Published2015 Jun 1
ISSN1944-7884
KeywordsAdolescent, Adult, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, Cystatin C, Female, HIV Infections, Humans, Inflammation, Male, Middle Aged, Plasma, Treatment Outcome, Young Adult
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.

DOI10.1097/QAI.0000000000000557
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID26009829
PubMed Central IDPMC4445470
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