Historical and current issues in HIV encephalitis, and the role of neuropathology in HIV disease: a pathological perspective

Abstract

In the 1980s, after the HIV pandemic was recognised, neuropathology identified cerebral white matter lesions that were found in the brains of infected persons with a severe irreversible dementia syndrome, this became known as ‘HIV encephalitis’. Subsequent work in Europe and north America found subtle morphological abnormalities in cerebral neurones and their connections. With the advent of effective anti-retroviral therapies after 1996, the incidence of severe HIV-related dementia declined, as did investigative tissue pathology into this HIV brain disease. Currently, the intense interest over HIV neurocognitive impairment focuses on neuroimaging, comparative blood and cerebrospinal fluid analysis, viral subtype analysis, and the search for biomarkers that correlate with brain function. Tissue neuropathology in HIV is more restricted to the diagnosis of acute disease such as opportunistic infections and tumours, and confirmation of the acute CD8 + T-cell encephalitis syndrome. But correlative tissue pathology will still be needed as newer therapeutic measures are developed to prevent and manage chronic HIV brain impairment.

The relationship between HIV‐1 neuroinflammation, neurocognitive impairment and encephalitis pathology: A systematic review of studies investigating post‐mortem brain tissue

“…The eligibility criteria for publications to be included in this study were those that investigated HIV‐positive treatment‐experienced adults (>18 years old, all medication types included and no cut‐off for treatment duration) with neuropsychological/neuropathological and medical assessments. The terms HIVE and HAND are often used interchangeably, however, this remains controversial 9 . For this review, we considered participants to have (1) HIVE when diagnosed using histopathological analysis and (2) clinical NCI when diagnosed using a neuropsychological examination.…”

“…The terms HIVE and HAND are often used interchangeably, however, this remains controversial. 9 For this review, we considered participants to have (1) HIVE when diagnosed using histopathological analysis and (2) clinical NCI when diagnosed using a neuropsychological examination. It is important to note that the pathology of HIV‐associated encephalitis (HIVE) has various forms and classifications 9 , 21 and therefore, these factors were taken into consideration during the inclusion strategy.…”

“…6 Studies with cell cultures and animals provide compelling evidence that HIV-1 induces neuronal damage and cell death through direct and indirect mechanisms, leading to the development of HIV-encephalitis (HIVE) neuropathology and clinical HAND. [7][8][9] With the introduction of antiretroviral therapy (ART), the most severe form of HAND, HIV-associated dementia (HAD), has dramatically declined. 2,10,11 However, mild neurocognitive disorder and asymptomatic neurocognitive impairment have increased and are present in half of the population of PLWH.…”

“…Once within the CNS, the virus primarily infects microglia, the resident macrophages in the CNS 6 . Studies with cell cultures and animals provide compelling evidence that HIV‐1 induces neuronal damage and cell death through direct and indirect mechanisms, leading to the development of HIV‐encephalitis (HIVE) neuropathology and clinical HAND 7–9 …”

Neuro‐HIV—New insights into pathogenesis and emerging therapeutic targets

“…Chronic neuroinflammation is widely accepted as a major contributor to HAND as well as other neurodegenerative diseases 81 . In the ART era, the majority of virologically suppressed HAND patients do not display pathological evidence of severe encephalitis, 82 and under physiological conditions, low‐level inflammation in the brain is usually asymptomatic 83 . Nevertheless, elements of inflammation in the brain, such as accumulation of mononuclear phagocytes, related microglial activation and astrocytosis, and decreased synaptic and dendritic density, are observed in postmortem samples from HIV patients 84 .…”