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Elevated sCD163 in plasma but not cerebrospinal fluid is a marker of neurocognitive impairment in HIV infection

Burdo, Tricia H.a; Weiffenbach, Allisona; Woods, Steven P.b; Letendre, Scottb; Ellis, Ronald J.b; Williams, Kenneth C.a

doi: 10.1097/QAD.0b013e32836010bd
Basic Science

Objective: Here we evaluated whether neurocognitive disorders in HIV-infected individuals on effective antiretroviral therapy (ART) are associated with persistent monocyte activation as indexed by levels of soluble CD163 (sCD163), shed by monocyte/macrophages.

Design: Chronically, HIV-infected individuals were examined at two consecutive visits median [interquartile range (IQR)] 16 (7–32) months apart. All patients were on ART and durably virologically suppressed (plasma HIV RNA <50 copies/ml) at all visits. Thirty-four age-matched HIV-seronegative patients were used as controls.

Methods: A global deficit score (GDS) was calculated based on comprehensive neuropsychological assessment according to standard methods. Neuropsychological and medical data were used to assign neurocognitive status according to published guidelines for HIV-associated neurocognitive disorders (HAND) as follows: neuropsychologically normal (NP-nml), asymptomatic neuropsychological impairment (ANI) and minor neurocognitive disorder (MND). sCD163 in plasma and cerebrospinal fluid was measured using ELISA.

Results: GDS-impaired patients had higher plasma sCD163 than those who were not impaired [median (IQR) 1401 ng/ml (1057–2258) versus 955 ng/ml (586–1313); Wilcoxon P = 0.028]. Patients with MND (N = 6) had significantly higher plasma sCD163 than ANI (P = 0.04) or NP-nml (P = 0.02). Whereas plasma sCD163 levels dropped in patients who were stably GDS-unimpaired after the first visit (P < 0.032), levels remained elevated in those who remained GDS-impaired (P = 0.50).

Interpretation: These findings are consistent with persistent monocyte/macrophage activation in neurophysiologically impaired HIV-infected individuals despite virally suppressive ART. Overall, these observations underscore the significance of monocyte/macrophage immune responses in HIV, persistent monocyte activation in HAND and the value of sCD163, as a plasma marker of neurocognitive impairment.

aDepartment of Biology, Boston College, Chestnut Hill, Massachusetts

bHIV Neurobehavioral Research Center, University of California San Diego, San Diego, California, USA.

Correspondence to Kenneth C. Williams, Department of Biology- Boston College, 140 Commonwealth Avenue Higgins Hall 468, Chestnut Hill, MA 02467, USA. Tel: +1 617 552 1186; fax: +1 617 552 2011; e-mail:

Received 15 November, 2012

Revised 25 January, 2013

Accepted 11 February, 2013

© 2013 Lippincott Williams & Wilkins, Inc.