HIV-Associated CD8 Encephalitis: A UK Case Series and Review of Histopathologically Confirmed Cases.

Sebastian B Lucas,Kum T Wong,Robert F Miller,Sam Nightingale

doi:10.3389/fneur.2021.628296

Abstract

HIV-associated CD8-encephalitis (HIV-CD8E) is a severe inflammatory disorder dominated by infiltration of the brain by CD8+ T-lymphocytes. It occurs in people with HIV, typically when the virus is apparently well-controlled by antiretroviral treatment (ART). HIV-CD8E presents with symptoms and signs related to marked cerebral inflammation and swelling, and can lead to coma and death unless treated promptly with corticosteroids. Risk events such as intercurrent infection, antiretroviral therapy interruption, immune reconstitution inflammatory syndrome (IRIS) after starting ART, and concomitant associations such as cerebrospinal fluid (CSF) HIV viral escape have been identified, but the pathogenesis of the disorder is not known. We present the largest case series of HIV-CD8E to date (n = 23), representing histopathologically confirmed cases in the UK. We also summarize the global literature representing all previously published cases with histopathological confirmation (n = 30). A new variant of HIV-CD8E is described, occurring on a background of HIV encephalitis (HIVE).Together these series, totalling 53 patients, provide new insights. CSF HIV viral escape was a frequent finding in HIV-CD8E occurring in 68% of those with CSF available and tested; ART interruption and IRIS were important, both occurring in 27%. Black ethnicity appeared to be a key risk factor; all but two UK cases were African, as were the majority of the previously published cases in which ethnicity was stated. We discuss potential pathogenic mechanisms, but there is no unifying explanation over all the HIV-CD8E scenarios.

Highlights

In 2002, we [SL, RM] documented the first case of what is termed HIV-associated CD8 encephalitis (HIV-CD8E)—an inflammatory cerebral disease dominated by severe infiltration of the cerebrum by CD8+ T-cells (1)
HIV-CD8E is clinico-pathologically distinct from classical “HIV encephalitis (HIVE)” where pathology shows HIV-containing microglial cells on immunohistochemistry, microglial nodules, microglial giant cells and few T-cells (3, 4), and which presents with a sub-acute to chronic subcortical dementia syndrome
From 2002-February 2021, we identified, in the UK, 23 adults infected with HIV-1 who had HIV-CD8E, diagnosed at autopsy (n = 19) or on brain biopsy (n = 4)

Summary

Introduction

In 2002, we [SL, RM] documented the first case of what is termed HIV-associated CD8 encephalitis (HIV-CD8E)—an inflammatory cerebral disease dominated by severe infiltration of the cerebrum by CD8+ T-cells (1). CD8+ T-cell infiltration of the brain is not unique to HIV infection, occurring in many other encephalitis syndromes (infectious, autoimmune, and idiopathic), where diffuse and perivascular CD8+ T-cell infiltrates are seen histopathologically in the brain (2). Over two decades, this syndrome has come to be recognized by clinicians as an uncommon complication occurring in some patients being treated with ART. Definitive diagnosis is made on brain biopsy or at autopsy, where diffuse, predominantly white matter, infiltration by CD8+ T-cells is seen (normal brains do not have T-cells visible in the parenchyma, only within the vasculature). HIV-CD8E is clinico-pathologically distinct from classical “HIV encephalitis (HIVE)” where pathology shows HIV-containing microglial cells on immunohistochemistry, microglial nodules, microglial giant cells and few T-cells (3, 4), and which presents with a sub-acute to chronic subcortical dementia syndrome

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