Cerebrospinal Fluid and Plasma Lipopolysaccharide Levels in Human Immunodeficiency Virus Type 1 Infection and Associations With Inflammation, Blood-Brain Barrier Permeability, and Neuronal Injury

Abstract

Human immunodeficiency virus (HIV) infection is associated with increased systemic microbial translocation, neuroinflammation, and occasionally, neuronal injury. Whether systemic lipopolysaccharide (LPS) penetrates into the brain and contributes to neuroinflammation remain unknown in HIV. Here, we measured plasma and cerebrospinal fluid (CSF) LPS levels along with biomarkers of neuroinflammation (white blood cell counts and 40 soluble markers) and neurofilament light chain (NfL). Notably, CSF LPS was undetectable in all samples, including 3 HIV-infected individuals with dementia. Increased plasma LPS, neuroinflammation, and blood-brain barrier (BBB) dysfunction were found in untreated HIV-infected individuals, but not in healthy or treated HIV-infected individuals. Plasma LPS levels were directly correlated with various markers of inflammation in both plasma and CSF, as well as with degree of BBB permeability but not with CSF NfL in HIV-infected subjects. These results suggest that the magnitude of microbial translocation associates with neuroinflammation and BBB permeability in HIV without direct penetration into the central nervous system.

Keywords: HIV-1 infection; blood-brain barrier permeability; cerebrospinal fluid; lipopolysaccharide; neuroinflammation; neuronal injury.