Peripheral biomarkers do not correlate with cognitive impairment in highly active antiretroviral therapy–treated subjects with human immunodeficiency virus type 1 infection

Abstract

Neuropsychological (NP) impairments in human immunodeficiency virus (HIV)-infected individuals remain high despite the introduction of highly active antiretroviral therapy (HAART). We sought to determine whether or not a monocyte gene expression profile along with other peripheral factors would correlate with neuropsychological impairment among HIV-infected individuals. Forty-four HIV-1-seropositive subjects (HIV+) on HAART and 11 HIV-1-seronegative controls (HIV-) had NP testing and blood drawn for monocyte gene expression analysis. All HIV+ subjects were assessed for CD4 counts, apolipoprotein E (ApoE) genotype, viral load, and plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14). NP scores were normalized to age, gender, and education. Twenty-five percent of HIV+ individuals showed abnormal NP testing results (> 1.5 SD below normal in two domains). HIV+ individuals had deficits in attention/working memory, verbal learning, and information processing speed compared to HIV- controls. There was no correlation between overall NP impairment and plasma viral load, level of education, age, ethnic diversity, sCD14, plasma LPS, CD4 cell count, ApoE genotype, or years of infection. However, greater years of infection had worse visual learning performance. sCD14 and CD4 nadir positively correlated with information processing speed and fine motor skills, respectively. LPS correlated with viral load but not cognitive impairment. Monocyte gene expression confirmed a chronic inflammatory profile that correlated with viral load but not cognition. No blood index or profile was associated with overall NP impairment.

A peripheral monocyte interferon phenotype in HIV infection correlates with a decrease in magnetic resonance spectroscopy metabolite concentrations

“…We previously reported a type 1 interferon (IFN)-α-driven monocyte phenotype in individuals with chronic HIV infection that correlated with viral load [9,10]. Here, we show that a monocyte IFN-α activation profile and IFN-gamma-inducible protein-10 (IP-10, CXCL10) in the plasma of HIV-positive individuals correlated with lower concentrations of NAA in the frontal white matter (FWM) measured by 1 H MRS.…”

“…All HIV-positive individuals were on stable ART or treatment interruption. Neuropsychological testing assessed seven domains of cognitive function and cognitive impairment was defined as more than 1.5 SD below the norm in at least two domains [9]. A global deficit score (GDS) was calculated with 0 being normal and a GDS at least 0.5 defined as mildly impaired [11].…”

“…Monocyte isolation, gene expression microarrays, and statistical methods have been previously described [9,10]. Total RNA was isolated and hybridized to Codelink Human Whole Genome Bioarrays (Applied Microarrays, Tempe, Arizona, USA).…”

HIV-1-Related Central Nervous System Disease: Current Issues in Pathogenesis, Diagnosis, and Treatment

“…However, although such markers have been correlated to disease activity, they have not been clinically used for diagnosis or monitoring of Neuro-AIDS owing to lack of specificity for active neurological disease in the setting of the immune activation characterizing HIV infection (Gisslén et al 2009). Recently, attention has turned to plasma markers related to immunopathogenesis of systemic HIV, including soluble CD14 and lipopolysaccharide (Ancuta et al 2008;Sun et al 2010). Direct markers of neurological injury assayed in CSF, including neurofilament light chain protein (NFL), tau protein, and precursors and products of amyloid protein (amyloid precursor proteins and Ab1-42) may be more valuable as measures of active neurodegeneration or injury (Hagberg et al 2000;Gisslen et al 2007Gisslen et al , 2009Clifford et al 2009).…”

Assessing the role of peripheral CD8 T cells in neurocognitive impairment in HIV-infected men who have sex with men: data from the MSM Neurocog Study

“…7,8 Although there is still limited evidence in the literature determining the role of CD8 T cells in HIV-related NCI, studies have suggested CD8 lymphocytes may be a possible marker for inflammation, which is believed to be a contributing factor to NCI. 9,10 The recent observation of CD4:CD8 ratio association with markers of age-associated disease in virally suppressed individuals with immunological recovery 11 strengthens the requirement for data on the role of CD8 T cells in NCI.…”