Plasma Cystatin C Associates With HIV-Associated Neurocognitive Disorder but Is a Poor Diagnostic Marker in Antiretroviral Therapy-Treated Individuals

J Acquir Immune Defic Syndr. 2019 Jun 1;81(2):e49-e54. doi: 10.1097/QAI.0000000000002016.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AIDS Dementia Complex / drug therapy
  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • Cognitive Dysfunction / complications
  • Cystatin C / blood*
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • Humans
  • Logistic Models
  • Male
  • Neurocognitive Disorders / complications
  • Neurocognitive Disorders / diagnosis*
  • Neuropsychological Tests
  • Odds Ratio
  • Plasma
  • Viral Load


  • Anti-Retroviral Agents
  • CST3 protein, human
  • Cystatin C

Grant support