jules levin, NATAP: HIV/AIDS-related dementia & cognitive dysfunctions (044)



Here are a few articles I think would address your needs including a review of neurologic disease from CROI 2009


Mechanisms of Neuronal Injury and Death in HIV-1 Associated Dementia – (10/24/08)
Infection with the human immunodeficiency virus-1 (HIV-1) and acquired immunodeficiency syndrome (AIDS) remain a persistent and even growing health problem worldwide. Besides its detrimental systemic effects on the immune system, HIV-1 seems to enter the brain very soon after peripheral infection and can induce severe and debilitating neurological problems that include behavioral abnormalities, motor dysfunction and frank dementia.

Infected peripheral immune cells, in particular macrophages, appear to infiltrate the CNS and provoke a neuropathological response involving all cell types in the brain. Both viral and host factors, such as the viral strain and the response of the host’s immune system, strongly influence the course of HIV-1 disease. Moreover, HIV 1-dependent disease processes in the periphery have a substantial effect on the pathology developing in the central nervous system (CNS), although the brain eventually harbors a distinctive viral population of its own. In the CNS, HIV-1 also initiates activation of chemokine receptors, inflammatory mediators, extracellular matrix-degrading enzymes and glutamate receptor-mediated excitotoxicity, all of which can activate numerous downstream signaling pathways and disturb neuronal and glial function. Although there have been substantial improvements in the control of viral infection in the periphery, an effective therapy for HIV-1 associated dementia (HAD) is still not in sight. This article will review recently identified injurious mechanisms potentially contributing to neuronal death in association with HIV-1 disease and discuss recent and prospective approaches for therapy and prevention of HAD.
“Mood changes approaching the extent of disorders are one of many problems associated with HIV-1 disease”

“Neuronal death by apoptosis appears to be one of the hallmarks of neurodegenerative diseases including HAD”

“While HAART has tremendously improved the treatment of HIV-1 infection and disease in the periphery, an effective pharmacotherapy for HAD (HIV-associated dementia) is still not available.”
“HAART is unlikely to prevent the entry of HIV-1 into the CNS”

“Neuronal damage and loss has been observed in distinct brain regions, including frontal cortex”……”signs of neuronal death were not clearly associated with viral burden or a history of dementia”….”aging-associated amyloid accumulation with Alzheimer’s-like neuropathology”….. “Altogether, it seems that a vicious cycle of immune dysregulation, inflammation and BBB dysfunction is required on the side of the host to allow sufficient entry of infected or activated immune cells into the brain and to permit neuronal injury”
“These findings suggest that inflammatory cytokines, including TNF-aand IL-1beta, may have important regulatory roles in HIV-associated neuropathology”

Neurologic Complications of HIV Disease and Their Treatment

The widespread use of ART has led to a decline in the more severe neurologic complications
of HIV, such as HAD, but people living with HIV continue to 

HIV-1 Infection Is Associated With an Earlier Occurrence of a 

“We examined whether the FRP was more likely to occur among individuals with comorbidities of cancers and neurological disorders, ascertained according to 

Neurological/Cognitive Impairment on HAART: 50% on HAART have 

Many factors likely contribute to ongoing neurologic complications despite the ability of current drugs to profoundly suppress viral replication. 

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