Elevated sCD163 in NP impaired HIV+ individuals despite virally suppressive ART.

Type: Published Abstract
Title: Elevated sCD163 in NP impaired HIV+ individuals despite virally suppressive ART.
Authors: Burdo T, Weiffenbach A, Woods S, Letendre L, Ellis R, Williams K
Year: 2012
Publication: 19th Conference on Retroviruses and Opportunistic Infectons
Volume: Issue: Pages:
Abstract:Background: Recent data suggests that persistent monocyte/macrophage activation despite durable virologic suppression in HIV-infected individuals on antiretroviral therapy (ART) may contribute to persistent and disabling neurocognitive impairment. Here we evaluated whether neurocognition in HIV-infected individuals on effective ART is associated with persistent monocyte activation. We have previously demonstrated that plasma soluble CD163 (sCD163) correlated with monocyte expansion from bone marrow, the rate of AIDS progression and severity of macrophage-mediated pathogenesis in SIV-infected macaques and HIV-infected humans. Recently, we have demonstrated that monocyte activation persists despite ART, particularly among those where ART was not initiated early (within 1 year). Methods: 34 chronically HIV-infected individuals were used in this study and examined on two visits (5 to 42 months apart). All subjects were on ART and durably virologically suppressed (plasma HIV RNA <50c/mL at all visits). 34 age-matched HIV-seronegative subjects were used as controls. Neurological/neuropsychological (NP) assessment was performed at both visits and NP impairment was defined as Global Deficit Score (GDS) ≥ 0.5. sCD163 and sCD14 in plasma and CSF was measured using ELISA. Results: HIV-infected subjects were mostly middle-aged white men (median age 42, 91% male, 68% white) with 50% subjects having AIDS (CDC category C and/or CD4 count < 200). At the first visit, NP impaired subjects had higher plasma sCD163 levels than those who were NP normal (median [IQR] 1401 ng/mL [1057, 2258] versus 955 ng/mL [586, 1313]; Wilcoxon p=0.028) (Figure). Of the 13 subjects who were impaired at the first visit, 10 remained impaired at the second visit, and all but one of the 21 NP normal subjects remained normal. Subjects who remained impaired showed little change in their baselineadjusted sCD163 level, while those who remained normal showed a drop in baselineadjusted sCD163 (least squares means, -1.1 versus -280; p=0.056). sCD14 was not different between NP impaired and normal subjects. Discussion: These findings are consistent with abnormal mononuclear cell activation in NP impaired HIV+ individuals despite virally suppressive ART. Overall, these observations underscore the significance of monocyte/macrophage activation, immune responses in HIV pathogenesis, the role of persistent monocyte activation in HAND and the value of sCD163 as a marker of neurocognitive impairment.