Chapter 14 : The Neuropathology of HIV Pre- and Post-HAART

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This chapter presents (i) unifying neuropathological criteria for diagnosing HIV encephalopathy to decrease variability in diagnostic terms and criteria, (ii) an overview of the neuropathology of HIV infection, and (iii) data to show that highly active antiretroviral therapy (HAART) can reduce the severity of HIV encephalopathy but does not prevent monocyte trafficking to the brain. To determine the prevalence of HIV encephalopathy in autopsies before and after the introduction of HAART in 1995-1996, a group of physicians in Frankfurt, Germany, reevaluated neuropathology reports of autopsies performed on 436 HIV-infected patients between 1985 and 1999 at the Edinger Institute. Throughout the study period, HIV encephalopathy was the most common histological finding and the only neuro-AIDS complication that increased over time; the prevalence of cytomegalovirus (CMV), toxoplasmosis, cryptococcosis, and central nervous system (CNS) lymphoma decreased. The diagnosis of CMV infection of the brain required the identification of cells with the characteristic cytoplasmic and intranuclear inclusions of CMV. Gross examination of the brain and spinal cord at autopsy may reveal no lesions specific for HIV encephalopathy. Brain atrophy is present in severe cases and can be mild to marked, with hydrocephalus ex vacuo. New neuropsychological impairment was twice as common in the pre-HAART group as in the post-HAART group and occurred sooner in the course of HIV. The treatment of choice for HIV dementia and HIV-associated neurocognitive decline is HAART.

Citation: Neuenburg J. 2009. The Neuropathology of HIV Pre- and Post-HAART, p 181-199. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch14
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In the era of HAART (1996 to 1999), the prevalence of AIDS-related opportunistic infections of the brain is decreasing, but the prevalence of HIV encephalopathy is increasing. Data are from .

Citation: Neuenburg J. 2009. The Neuropathology of HIV Pre- and Post-HAART, p 181-199. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch14
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Image of FIGURE 2

Percentages and absolute counts of activated monocytes (CD14/CD16) in the CSF and blood. Patients on PI-containing regimens had a higher percentage of activated monocytes in CSF than uninfected controls (HIV–), patients off treatment (Off ART), or patients on a non-PI-containing regimen (No PI) (A). Absolute counts of activated monocytes in CSF show a similar profile (C). In blood, the highest percentage of activated monocytes was found in the uninfected controls (B). Absolute counts of activated monocytes in blood did not differ significantly but were highest in uninfected controls (D). Data are from .

Citation: Neuenburg J. 2009. The Neuropathology of HIV Pre- and Post-HAART, p 181-199. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch14
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Image of FIGURE 3

Proposed model of increased monocyte trafficking to the central nervous system in HIV infection and during ART. HIV infection leads to increased monocyte trafficking from bone marrow via blood into the perivascular area of the brain, which drains into the CSF. HIV can activate monocytes, and the activated monocytes are usually CD16. ART can lead to increased levels of LDL cholesterol in plasma; HIV and maybe ART lead to increased levels of CRP (which binds to Fcγ receptors [ ], such as CD16). Increases in LDL and CRP can upregulate the expression of CCR2, a chemokine receptor that is important in monocyte trafficking through its ligand monocyte chemoattractant protein 1 (MCP-1). Increased expression of CCR2 increases chemotaxis.

Citation: Neuenburg J. 2009. The Neuropathology of HIV Pre- and Post-HAART, p 181-199. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch14
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Generic image for table

Frankfurt criteria for diagnosing HIV encephalopathy, related to Consensus Report (also see Table 2 )

Citation: Neuenburg J. 2009. The Neuropathology of HIV Pre- and Post-HAART, p 181-199. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch14
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Criteria for diagnosing mild, moderate, severe, any HIV encephalopathy

Citation: Neuenburg J. 2009. The Neuropathology of HIV Pre- and Post-HAART, p 181-199. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch14
Generic image for table

HIV-related brain pathology at autopsy

Citation: Neuenburg J. 2009. The Neuropathology of HIV Pre- and Post-HAART, p 181-199. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch14
Generic image for table

CNS involvement and prevalence of opportunistic and HIV-related diseases in autopsy series

Citation: Neuenburg J. 2009. The Neuropathology of HIV Pre- and Post-HAART, p 181-199. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch14
Generic image for table

Hypothesized strategies for augmenting the beneficial effect of HAART on HIV dementia

Citation: Neuenburg J. 2009. The Neuropathology of HIV Pre- and Post-HAART, p 181-199. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch14

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