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 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.

• Authors: Chris T Longenecker, Douglas Kitch, Paul E Sax, Eric S Daar, Camlin Tierney, Samir K Gupta, Grace A McComsey, AIDS Clinical Trials Group Study A5224s Team
• Journal: Journal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 69 Issue 2 Pg. 168-77 (Jun 01 2015) ISSN: 1944-7884 [Electronic] United States
• PMID: 26009829 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Retroviral Agents
• Cystatin C

Topics

• Adolescent
• Adult
• Anti-Retroviral Agents (therapeutic use)
• Antiretroviral Therapy, Highly Active (methods)
• Cystatin C (blood)
• Female
• HIV Infections (drug therapy, pathology)
• Humans
• Inflammation (pathology)
• Male
• Middle Aged
• Plasma (chemistry)
• Treatment Outcome
• Young Adult