Human Pegivirus Encephalitis With Brain Detection and Response to Sofosbuvir Ledipasvir.

Human pegivirus (HPgV-1) has been associated with severe encephalomyelitis in immunocompromised patients. Its neurological spectrum remains poorly defined. We report a slowly progressive encephalitis in a person living with well-controlled HIV, characterized by white matter abnormalities and inflammatory cerebrospinal fluid (CSF). HPgV RNA was detected in CSF and brain tissue by metagenomic sequencing, with no alternative pathogen identified. Following off-label treatment with sofosbuvir/ledipasvir, the patient showed sustained clinical improvement, normalization of CSF findings, and disappearance of detectable HPgV RNA. This observation expands the clinical context of HPgV-1 detection and supports further investigation of its role in central nervous system disease.