Evaluation of HIV RNA and markers of immune activation as predictors of HIV-associated dementia

Abstract

The lack of association between baseline plasma and CSF HIV RNA levels and incident dementia suggests highly active antiretroviral therapy may be affecting CNS viral dynamics, leading to lower HIV RNA levels, and therefore weakening the utility of baseline HIV RNA levels as predictors of HIV-associated dementia.

CCR2 mediates increases in glial activation caused by exposure to HIV-1 Tat and opiates

“…As noted earlier, CCL2 levels are highly correlated with neurocognitive deficits accompanying HIV-1 or simian immunodeficiency virus infection (Sevigny et al, 2004;Mankowski et al, 2004;Avison et al, 2004;Chang et al, 2004), and CCL2 levels are markedly increased by substance abuse in HIV-1 infected individuals Hauser et al, 2006). Therapeutic strategies that interfere with endogenous CCR2 ligand-receptor interactions would likely be beneficial to HIV-1 infected individuals regardless of whether or not they abuse opiate drugs.…”

“…CCL2 attracts and activates mononuclear phagocytes, as well as several other leukocyte types, to sites of CNS injury (McManus et al, 2000). CCL2 levels correlate with neurocognitive deficits accompanying HIV-1 or simian immunodeficiency virus infection (Sevigny et al, 2004;Mankowski et al, 2004;Avison et al, 2004;Chang et al, 2004). Moreover, mutations in CCL2 and CCR2 affect HIV pathogenesis (Gonzalez et al, 2002;Letendre et al, 2004;Singh et al, 2004).…”

CCL2/Monocyte Chemoattractant Protein-1 Mediates Enhanced Transmigration of Human Immunodeficiency Virus (HIV)-Infected Leukocytes across the Blood–Brain Barrier: A Potential Mechanism of HIV–CNS Invasion and NeuroAIDS

“…Previous reports demonstrated that under normal conditions, there are baseline chemokine gradients within the CNS during microglia turnover and migration into the CNS and during development/synaptic plasticity and neuronal/ glial migration (Eglitis and Mezey, 1997;Male, 1997, 1999;Aarum et al, 2003). We propose that HIV-infected cells respond to the constitutively expressed CCL2 within the CNS to enter the brain by transmigrating across the CNS vasculature and causing transient BBB disruption, thereby remaining protected within the CNS, even after HAART treatment (Chun et al, 1997;Chang et al, 2003;Sevigny et al, 2004).…”

A comparison of two post-processing analysis methods to quantify cerebral metabolites measuredviaproton magnetic resonance spectroscopy in HIV disease

“…6 Furthermore, potential plasma biomarkers have shown little specificity in detecting HIV-associated cognitive disorders. 7 Although cerebrospinal fluid (CSF) markers are considered a more valuable clinical tool, 8 the requirement for CSF examination is challenging, and less invasive methods are preferable. Measurement of cerebral metabolites as biomarkers, via proton-MR spectroscopy ( 1 H-MRS), is one attractive approach for the assessment of cerebral function in HIV disease.…”