HIV-associated CD8 encephalitis: role of metagenomics in complex CNS presentations

We describe a 54-year-old woman living with HIV who presented with a tonic-clonic seizure and rapidly progressive encephalitis. Despite an undetectable plasma viral load while taking Biktarvy, initial investigations revealed cerebrospinal fluid escape with an HIV viral load of 474 copies/mL. Extensive testing for opportunistic infections and autoantibodies was negative. Brain biopsy and metagenomic next-generation sequencing identified frequent CD8+ T-cell infiltration and human pegivirus, though the latter was deemed a bystander. The patient’s condition improved significantly, notably without the high-dose corticosteroids typically required for CD8+ encephalitis. This recovery suggests a moderate, self-limiting phenotype of the disease. The case highlights the diagnostic utility of metagenomics in complex presentations while cautioning against the misinterpretation of non-pathogenic commensals.