Robert C Kalayjian1,2,3, Kevin R Robertson4, Jeffrey M Albert3,5, Carl J Fichtenbaum6, Todd T Brown7, Babafemi O Taiwo8. 1. Division of Infectious Diseases, Department of Medicine, MetroHealth Med Center, Cleveland, OH. 2. Division of Infectious Diseases, Department of Medicine, Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH. 3. Infectious Diseases, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH. 4. Department of Neurology, University of North Carolina School of Medicine, Chapel Hill, NC. 5. Department of Population and Quantitative Health Science, Case Western Reserve University School of Medicine, Cleveland, OH. 6. Division of Infectious Diseases, Department of Medicine, University of Cincinnati School of Medicine, Cincinnati, OH. 7. Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. 8. Division of Infectious Diseases, Department of Medicine, Northwestern University School of Medicine, Chicago, IL.
Abstract
OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: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.
RCT Entities:
OBJECTIVE: 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). METHODS: 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. RESULTS: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. CONCLUSIONS: 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.
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