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Higher Cystatin C Levels Are Associated With Neurocognitive Impairment in Older HIV+ Adults

Sakoda, Marissa E. BA; Fazeli, Pariya L. PhD; Ellis, Ronald J. MD, PhD; Jeste, Dilip V. MD; Grant, Igor MD; Letendre, Scott L. MD; Moore, David J. PhD

JAIDS Journal of Acquired Immune Deficiency Syndromes: March 1st, 2017 - Volume 74 - Issue 3 - p 243–249
doi: 10.1097/QAI.0000000000001235

Objective: The study aims to determine whether cystatin C is associated with HIV disease and HIV-associated neurocognitive impairment (NCI).

Methods: Participants included 124 (HIV+ n = 77; HIV− n = 47) older adults (age ≥ 50 years) examined at the University of California, San Diego HIV Neurobehavioral Research Program. Cystatin C, a biomarker of kidney functioning that has been linked to poor health outcomes, was measured in blood. Participants completed a comprehensive neurocognitive assessment that was used to define both global and domain NCI.

Results: The HIV+ group had significantly higher cystatin C concentrations than the HIV− group (d = 0.79 P < 0.001). Among HIV+ participants, those with NCI had higher cystatin C concentrations than those without NCI (d = 0.42, P = 0.055), particularly among participants taking tenofovir (d = 0.78, P = 0.004). A receiver–operator characteristic curve identified that cystatin C levels ≥0.75 mg/L were associated with NCI in the HIV+ group. Using this binary variable and including relevant covariates, multivariate modeling confirmed that NCI was associated with higher cystatin C levels (OR = 3.0; P = 0.03).

Conclusions: Our results confirm that HIV+ older adults have higher cystatin C than HIV− older adults and further identify that cystatin C may be associated with NCI in this population, particularly if they use tenofovir. This blood biomarker may be a useful clinical tool to identify older HIV+ persons at greater risk for cognitive decline.

*Department of School of Medicine, John A. Burns School of Medicine, University of Hawaii Honolulu, HI;

Departments of Psychiatry;

Neurosciences, University of California, San Diego, San Diego, CA;

§Stein Institute for Research on Aging, University of California, San Diego, San Diego, CA; and

Department of Medicine, University of California, San Diego, San Diego, CA.

Correspondence to: David J. Moore, PhD, HIV Neurobehavioral Research Program, 220 Dickinson Street, Suite B, San Diego, CA 92103-8231 (e-mail:

Supported by the California HIV/AIDS Research Program IDEA Award ID10-SD-057 (PI: D.J.M.), NIH K24 MH097673 (PI: S.L.L.), and NIH K99/R00 AG048762 (P.I. P.L.F.). M.E.S. was funded by the UC San Diego Medical Student Aging Research Training Grant (NIH T35 AG026757; PI: D.V.J.). The study was more broadly supported by R01 MH099987 (MPI: D.V.J./D.J.M.) and the HIV Neurobehavioral Research Center (HNRC) Center award P30 MH062512 (PI: Heaton, Robert). University of California, San Diego has received research funding on behalf of Dr. Letendre (SLL) from Gilead Sciences. While these funds do not support research related to this project, Gilead is the manufacturer of tenofovir, use of which was included in some analyses. The remaining authors have no funding or conflicts of interest to disclose.

Presented at the Conference of Retroviruses and Opportunistic Infections, February 23–26, 2015, Seattle, WA.

The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, nor the United States Government.

Received June 17, 2016

Accepted October 14, 2016

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