Enrichment of activated monocytes in cerebrospinal fluid during antiretroviral therapy

Neuenburg, Jutta K.; Furlan, Scott N.; Bacchetti, Peter; Price, Richard W.; Grant, Robert M.

doi:10.1097/01.aids.0000181008.39514.ee

Cited by 16 publications

(7 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One group (Neuenburg, Furlan, Bacchetti, Price, & Grant, 2005) measured this subset in a large number of patients although none was demented. Patients who were on a HAART regimen containing a protease inhibitor were the most likely to have significant elevations in this monocyte subset in the CSF.…”

Section: Monocytesmentioning

confidence: 99%

Biomarkers of HIV related central nervous system disease

Brew

Letendre

2008

International Review of Psychiatry

View full text Add to dashboard Cite

In this review we critically assess biomarkers of the direct effects of HIV related brain disease. This area is becoming increasingly complex because of the presence of confounds and varying degrees of activity of HIV brain disease. Sensitive and specific biomarkers are urgently needed although existing biomarkers do have some utility. The review will focus on the practical implications of the more established biomarkers. We discuss blood, cerebrospinal fluid and neurophysiological biomarkers but not neuroimaging techniques as they are beyond the scope of this review.

show abstract

Section: Monocytesmentioning

confidence: 99%

Biomarkers of HIV related central nervous system disease

Brew

Letendre

2008

International Review of Psychiatry

View full text Add to dashboard Cite

show abstract

“…The etiology of persistent cognitive deficits in patients on ART remains unclear. Studies of cerebrospinal fluid from individuals with HAND have sometimes supported contradictory conclusions; in the absence of viral replication, some authors observe associations among dementia, abnormal neurometabolites, and inflammatory phenotypes; others, with non-inflammatory states or markers of neurodegeneration [12]–[16]. There have been limited studies of brain tissues from treated patients with HAND to evaluate what biologic pathways remain abnormally regulated under ART, with studies largely focused on single cell types or molecules [17].…”

Section: Introductionmentioning

confidence: 99%

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-1-Associated Neurocognitive Disorders

et al. 2011

View full text Add to dashboard Cite

Antiretroviral therapy (ART) has reduced morbidity and mortality in HIV-1 infection; however HIV-1-associated neurocognitive disorders (HAND) persist despite treatment. The reasons for the limited efficacy of ART in the brain are unknown. Here we used functional genomics to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed genome-wide microarray analysis using Affymetrix U133 Plus 2.0 Arrays, real-time PCR, and immunohistochemistry in brain tissues from seven treated and eight untreated HAND patients and six uninfected controls. We also determined brain virus burdens by real-time PCR. Treated and untreated HAND brains had distinct gene expression profiles with ART transcriptomes clustering with HIV-1-negative controls. The molecular disease profile of untreated HAND showed dysregulated expression of 1470 genes at p<0.05, with activation of antiviral and immune responses and suppression of synaptic transmission and neurogenesis. The overall brain transcriptome changes in these patients were independent of histological manifestation of HIV-1 encephalitis and brain virus burdens. Depending on treatment compliance, brain transcriptomes from patients on ART had 83% to 93% fewer dysregulated genes and significantly lower dysregulation of biological pathways compared to untreated patients, with particular improvement indicated for nervous system functions. However a core of about 100 genes remained similarly dysregulated in both treated and untreated patient brain tissues. These genes participate in adaptive immune responses, and in interferon, cell cycle, and myelin pathways. Fluctuations of cellular gene expression in the brain correlated in Pearson's formula analysis with plasma but not brain virus burden. Our results define for the first time an aberrant genome-wide brain transcriptome of untreated HAND and they suggest that antiretroviral treatment can be broadly effective in reducing pathophysiological changes in the brain associated with HAND. Aberrantly expressed transcripts common to untreated and treated HAND may contribute to neurocognitive changes defying ART.

show abstract

“…However, there continue to be reports suggesting central nervous system (CNS) involvement in patients treated with ART. These include evidence of neuropsychological impairments (Rothlind et al , 2005; Tozzi et al , 2007), abnormal brain electrical activity related to cognition (Chao et al , 2003), brain changes detected by MRI (Ances et al , 2006) or MR spectroscopy (Chang et al , 2003; Schweinsburg et al , 2005; Roc et al , 2007), alterations in CSF markers of monocyte activation (Neuenburg et al , 2005) and CNS injury, and brain pathology detected at autopsy (Neuenburg et al , 2002). Previous research has not elucidated the extent to which these observations reflect brain alterations due to HIV infection before commencement of ART, or ongoing brain injury due to HIV despite ART.…”

Section: Introductionmentioning

confidence: 99%

Evidence for ongoing brain injury in human immunodeficiency virus–positive patients treated with antiretroviral therapy

et al. 2009

View full text Add to dashboard Cite

Treatment with antiretroviral therapy (ART) has greatly reduced the incidence of dementia. The goal of this longitudinal study was to determine if there are ongoing macrostructural brain changes in human immunodeficiency virus-positive (HIV+) individuals treated with ART. To quantify brain structure, three-dimensional T1-weighted magnetic resonance imaging (MRI) scans were performed at baseline and again after 24 months in 39 HIV+ patients on ART and 30 HIV− controls. Longitudinal changes in brain volume were measured using tissue segmentation within regions of interest and deformation morphometry. Measured by tissue segmentation, HIV+ patients on ART had significantly (all P < .05) greater rates of white matter volume loss than HIV− control individuals. Compared with controls, the subgroup of HIV+ individuals on ART with viral suppression also had significantly greater rates of white matter volume loss. Deformation morphometry confirmed these results with more specific spatial localization. Deformation morphometry also detected greater rates of gray matter and white matter loss in the subgroup of HIV+ individuals with detectable viral loads. These results provide evidence of ongoing brain volume loss in HIV+ individuals on stable ART, possibly suggesting ongoing cerebral injury. The presence of continuing injury raises the possibility that HIV+ individuals-even in the presence of viral suppression in the periphery-are at greater risk for future cognitive impairments and dementia and possibly faster cognitive decline. Therefore, HIV+ individuals on ART should be monitored for cognitive decline, and treatments that reduce ongoing neurological injury should be considered.

show abstract

Enrichment of activated monocytes in cerebrospinal fluid during antiretroviral therapy

Abstract: Activated monocytes are enriched in the CSF of persons living with HIV-1 and receiving ART. This finding is consistent with previously reported autopsy series. The mechanisms and long-term clinical consequences of persistent monocyte activation require further study.

Cited by 16 publications

References 57 publications

Biomarkers of HIV related central nervous system disease

Biomarkers of HIV related central nervous system disease

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-1-Associated Neurocognitive Disorders

Evidence for ongoing brain injury in human immunodeficiency virus–positive patients treated with antiretroviral therapy

Contact Info

Product

Resources

About