To examine associations between plasma cystatin C and neurocognitive impairment (NCI) and its performance as a diagnostic marker before and during initial antiretroviral therapy (ART).
Multivariable logistic regression and generalized estimating equations examined associations with NCI, determined by neuropsychological measurements, in participants of a 48-week randomized clinical trial of initial ART. Receiver operator characteristic curves examined diagnostic models of NCI.
Cystatin C was associated with NCI before ART [odds ratio (OR) 3.4 (95% CI: 1.2 to 9.4) for each 2-fold increase in baseline levels] and during 48 weeks of ART, in models that excluded baseline measurements [OR 3.0 (1.2 to 7.8) for each 2-fold increase in time-updated levels]. The strength of association increased with more severe impairment using HIV-associated neurocognitive disorder criteria [OR 2.2 (0.8 to 6.0) with asymptomatic NCI and OR 4.0 (1.5 to 11.0) with mild neurocognitive disorder or HIV-associated dementia vs. no impairment, for each 2-fold increase in time-updated levels] or by global development score [OR 2.6 (1.1 to 6.3) with mild impairment and OR 4.6 (1.1 to 18.9) with moderate or severe impairment vs. no impairment]. Cystatin C performed poorly as a diagnostic marker for NCI, however, with an area under the receiver operator characteristic curve of 0.58 at baseline and 0.54 at week 48.
Higher plasma cystatin C levels were significantly associated with NCI, but these levels did not seem to be useful as a diagnostic marker for this condition.
aDivision of Infectious Diseases, Department of Medicine, MetroHealth Med Center, Cleveland, OH;
bDivision of Infectious Diseases, Department of Medicine, Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH;
cInfectious Diseases, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH;
dDepartment of Neurology, University of North Carolina School of Medicine, Chapel Hill, NC;
eDepartment of Population and Quantitative Health Science, Case Western Reserve University School of Medicine, Cleveland, OH;
fDivision of Infectious Diseases, Department of Medicine, University of Cincinnati School of Medicine, Cincinnati, OH;
gDivision of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; and
hDivision of Infectious Diseases, Department of Medicine, Northwestern University School of Medicine, Chicago, IL.
Correspondence to: Robert C. Kalayjian, MD, Infectious Diseases, Department of Medicine, MetroHealth Medical Center, Case Western Reserve University School of Medicine, 2500 MetroHealth Dr., Cleveland, OH 44109 (e-mail: firstname.lastname@example.org).
Supported by Award Number U01AI068636 and P30 AI036219 from the National Institute of Allergy and Infectious Diseases and supported by the National Institute of Mental Health (NIMH), National Institute of Dental and Craniofacial Research (NIDC), the Veterans Administration: VISN10 Geriatric Research Education and Clinical Centers, Louis Stokes Cleveland Veterans Administration Medical Center; the ACTG Statistical Data Analysis Center (Grant numbers AI068634 and AI068636); and the research sites that participated: (Grant numbers UMAI069494, UMAI069432, UM1AI 069471, UM1AI069452, UM1 AI069501, 2UM1AI069432, UL1 TR001082, 1U01AI069477-01, P30AI073961, 5UM1 AI068636, 2UM1AI069503, UM1 AI069471, 2UM1AI069439-08, and UL1 TR000445 from the National Center for Advancing Translational Sciences/NIH AI69439, UM1 AI069496, 5UM1AI069412, UM1 AI069423, 1UL1TR001111, P30 AI50410, 2UMIA1069423-08, 2UM1AI069418-08, 2P30 AI 50409-10, UL1TR000454, AI069501, 5UM1AI069415-10, 2UM1AI069412-08, AI069424, UL1 RR025780, 2UM1 AI069470-08, UM1AI069472, 2UMAI069432, AI 69501, UM1AI069471, UM1A 068636-09, 5 P30 AI- 045008-15, U01AI069447, NO1-HD-3-3345, UMI AI069511, UM1 AI069465, UL1TR001079, UL1 RR024160, UL1 TR000042, and from the Center for AIDS Research AI 036219). ViiV, Gilead, and AbbVie provided study drugs. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.
R.C.K. receives research funding from Gilead Sciences; T.T.B. has received research funding from Gilead Sciences, Bristol-Myers Squibb, Merck, EMD-Serono, and Theratechnologies; B.O.T. has served as a consultant to ViiV, Pfizer, Janssen, GlaxoSmithKline (GSK), and Gilead, and has received research support to Northwestern University from ViiV and Pfizer. The remaining authors have no conflicts of interest to disclose.
R.C.K., B.O.T., and T.T.B., conceived of and led the study. R.C.K. and J.M.A. analyzed the data. All authors contributed to the writing and editing of the manuscript.
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Received December 12, 2018
Accepted February 11, 2019