Transcript HIV-1 Associated Dementia:

HIV-1 Associated
Dementia:
Symptoms & Causes
M. Ghafouri, S. Amini, K. Khalili, B. E. Sawaya
Summary by J.B. Leiknes, 4th Year GM
Charles University, Faculty of Medicine in Hradec Kralové
HIV-1 Associated Dementia
[HAD]
• Neurological impairment
affects ca 60% of patients
with HIV
• Occurs despite use of highly
active antiretroviral therapy
[HAART].
• Correlates with increased
presence of activated
microglia & CNS
macrophages.
Neuropathology of HAD
• Neurons are not productively infected
by HIV-1.
• Suggests indirect mechanisms of
neuronal injury/loss/death leading to
dementia.
Neuropathology of HAD
• Other factors can contribute to neuropathology of
AIDS: opportunistic infections like cryptococcus,
toxoplasmosis, JC virus, CMV, EBV, HHV-6,
Varicella zoster v.
• Major clinical symptoms (in absence of clear
infectious cause): impaired short term-memory
loss, reduced concentration, leg weakness,
slowness of hand movement & gait, depression
• Behavioral symptoms: personality changes,
apathy, social withdrawal
Pathogenesis of HAD
• HIV-1 targets lymphoid & nervous
systems by infecting cells with major
HIV-1 receptors: CD4 & CD8
• CD4 & CD8 facilitate attachment of virus
to cell membrane & entry into the cell
• Infected CD4+ T cells & monocytes
circulate in blood & are potential source
of CNS infection
Pathogenesis of HAD
• Mechanisms of
HIV-1 crossing
BBB remains
unclear
• Generally
accepted model:
“Trojan Horse
hypothesis”
Mechanism of
Neuropathogenesis
•
Two major components:
•
Direct effect of HIV-1
infection (including
HIV-1 proteins)
•
Indirect
consequence of
infection comprising
secretion of
cytokines &
neurotoxins
Source
• HIV-1 Associated
Dementia: Symptoms &
Causes
• M. Ghafouri, S. Amini, K. Khalili, B.E. Sawaya
•
Full-text online version in Retrovirology Volume 3:
http://www.retrovirology.com/content/3/1/28