CNS nontumor


Chronic / subacute infections

HIV encephalitis

Last author update: 1 June 2014
Last staff update: 17 May 2023

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PubMed Search: HIV encephalitis [title]

Mark Cohen, M.D.
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Cite this page: Cohen M. HIV encephalitis. website. Accessed May 19th, 2024.
Definition / general
  • HIV encephalitis refers to cognitive impairment resulting from productive cerebral infection by the human immunodeficiency virus
  • It does not apply to opportunistic infections resulting from generalized cell mediated immunodeficiency
  • Prior to successful implementation of combined antiretroviral therapy, severe cognitive impairment related to HIV encephalitis was also referred to as HIV associated dementia (HAD) or the AIDS dementia complex
  • Currently, other terms used to describe this illness include HIV associated neurocognitive disorder (HAND) and HIV associated neurocognitive impairment
  • It has been proposed that HIV neurocognitive impairment be divided into type I (corresponding to neurocognitive disability resulting from active HIV encephalitis) and type II (corresponding to mild cognitive impairment, for which the neuropathological substrate has not been established)
  • Although formally encountered as a severe dementia occurring in at least 20% of end stage AIDS patients with critically low CD4 counts and high viral loads, in the current era of combined antiretroviral therapies, the disease is now most commonly manifested as mild neurocognitive disability in clinically stable patients
  • Prevalence estimates for HIV associated neurocognitive disorder range from 35 to 100%
  • References: PLoS One 2012;7:e46178, J Infect Dis 2008;197:S294
  • Although HIV encephalitis may occur anywhere within the nervous system, there is a distinct predilection for pathologic changes to be found predominantly within subcortical white matter and basal ganglia
  • Monotropic strains of the HIV virus gain entrance to the nervous system within monocytes which easily traverse the blood brain barrier
  • Infected monocytes then fuse with resident microglial cells, resulting in activation with release of cytokines and other molecules which result in secondary brain injury
  • In addition, HIV associated glycoproteins may interfere with synaptic activity
  • However, neurons are not productively infected by the virus
  • References: PLoS Pathog 2011;7:e1002286, Am J Pathol 2010;176:893, Am J Pathol 2011;179:1623, Neurology 2013;80:1415
  • Currently, the diagnosis is made through the neuropsychometric performance testing, in combination with neuroimaging
  • Classical HIV disease biomarkers (low CD4 count, high viral load) are no longer closely associated with neurological impairment although markers of systemic inflammation appear to correlate with cognitive impairment
Radiology description
  • Characteristic neuroimaging appearance of HIV associated neurocognitive disorder is increased white matter signal on fluid level attenuated inversion recovery (FLAIR) images although these are only apparent in the more advanced stages of cognitive impairment
Radiology images

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Cranial MRI

Symmetric patchy periventricular

Case reports
  • Although implementation of combined antiretroviral therapy has reduced the prevalence of severe neurocognitive impairment, optimized HIV therapy is not sufficient to avert cognitive impairment (even when CNS penetrating antivirals are utilized)
  • It is believed that in addition to combined antiretroviral therapy, treatments that will address inflammation and cardiovascular risks may provide benefit
Gross description
  • Brain of patients with uncomplicated HIV encephalopathy shows no discernible gross abnormalities
  • In fact, the presence of gross abnormalities suggests the presence of additional pathologies related to immunosuppression
Microscopic (histologic) description
  • Similar to other viral infections of the nervous system, HIV encephalitis is characterized by the presence of microglial nodules
  • Unlike other viral infections, HIV stimulates fusion of microglial cells to form multinucleated microglial cells
  • In addition, the amount of lymphocytic inflammation is generally considerably less than that seen in viral infections of immunocompetent hosts
Microscopic (histologic) images

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Stained sections of the white matter

Positive stains
  • Several antibodies are available that recognize HIV associated glycoproteins
  • p24 shows reactivity within both perivascular mononuclear and multinucleate microglial cells
Differential diagnosis
  • Although the presence of superimposed opportunistic infections or neoplasms must always be kept in mind, the presence of subcortical microglial nodule encephalitis with multinucleated microglial cells is virtually pathognomonic for HIV encephalitis
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