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HIV-1 Associated Dementia:

HIV-1 Associated Dementia:

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HIV-1 Associated Dementia:

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  1. 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

  2. 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.

  3. Neuropathology of HAD • Neurons are not productively infected by HIV-1. • Suggests indirect mechanisms of neuronal injury/loss/death leading to dementia.

  4. 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

  5. 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

  6. Pathogenesis of HAD • Mechanisms of HIV-1 crossing BBB remains unclear • Generally accepted model: “Trojan Horse hypothesis”

  7. 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

  8. 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