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

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.

Post-Infectious Autoimmunity in the Central (CNS) and Peripheral (PNS) Nervous Systems: An African Perspective

“…Important risk factors include interruption of ART and IRIS after ART initiation. Although it is not known whether autoimmune mechanisms underpin this disease, treatment with corticosteroids improves outcome by reducing mortality ( 93 , 94 ).…”

HIV integration in the human brain is linked to microglial activation and 3D genome remodeling

“…From the sequenced libraries, we identified n=1,254 IS, the overwhelming majority (n=1,221/1254, 97%) of which came from NeuN-nuclei (Data file S10). Of note, IS were detected in 85% (6/7) of HIVE FC/WM donors and 28% (5/18) HIV + donors, including 2 subjects diagnosed with CD8+ T-cell encephalitis, an unusual inflammatory brain disorder often seen in cART-medicated individuals, but also in treatment-naïve individuals ( 36 ), and 1 elite controller (Fig. 4B).…”

Progressive hemispheric atrophy in HIV: A Rasmussen's‐like variant of CD8 encephalitis?

“…In descriptions of CD8E, microglial activation, gliosis, diffuse parenchymal and perivascular infiltrates of polyclonal CD8 > CD4 T cells involve primarily the white matter [1–3] but with bilateral involvement on histology and MRI [3, 4]. Although cortical involvement is recognised [2, 5, 6], this does not seem to be preferentially targeted and the extensive, progressive and lateralised cortical destructive lesions observed in the current cases are not typical features.…”

“…Cytotoxic CD8 + (Granzyme‐B/perforin‐positive) T cells in proximity to neurones and astroglia predominate over clonal γδ‐T and CD4 populations in the autoimmune cellular responses in active RE with fewer CD20 + cells [11]. Similar lymphocyte phenotypes were seen in Case 1 with active disease, but T cell subsets remain relatively unexplored in CD8E [4].…”