Comprehensive study of cerebrospinal fluid β2-microglobulin, a marker of central nervous system immune activation in individuals with HIV

OBJECTIVE: Cerebrospinal fluid (CSF) β 2 -microglobulin (β 2 M) has not been fully characterized in people with HIV (PWH) in different categories of disease. DESIGN: Retrospectively, we determined levels of β 2 M, neopterin, HIV RNA, albumin ratio, IgG index, CD4 + T-cell count, neurofilament light chain protein (NfL), and leukocyte counts (WBC), in CSF and blood in PWH with and without antiretroviral treatment (ART). Persons without HIV served as controls. METHODS: Participants were grouped as: neuroasymptomatic HIV (NA), NA CSF escape, symptomatic CSF escape, secondary CSF escape, HIV-associated dementia (HAD), opportunistic infections in the central nervous system (CNS) (OI), and elite controllers. RESULTS: We included 638 individuals: NA (N = 556); NA CSF escape ( N = 33); symptomatic CSF escape ( N = 4); secondary CSF escape ( N = 5); HAD ( N = 16); OI ( N = 18); elite controllers ( N = 6) and 59 controls. Highest CSF β 2 M levels were found in HAD, OI and symptomatic CSF escape. In 112 longitudinally followed NA participants, elevated CSF β 2 M levels (89%) were found at baseline, and 96% for CSF neopterin. After ART initiation, CSF β 2 M levels decreased by 10% per month and CSF neopterin by 17%. After 3 years, 39% had CSF β 2 M, and 44% had CSF neopterin levels above the reference values, similar to the controls (39%). CONCLUSION: CSF β 2 M levels were elevated in the majority of individuals across HIV stages. Suppressive ART decreases β 2 M toward control levels, although neuroinflammation persists, most likely driven by non-HIV factors.