Comprehensive study of cerebrospinal fluid Beta2-microglobulin, a marker of central nervous system immune activation in individuals with HIV

AIDS. 2026 Mar 6. doi: 10.1097/QAD.0000000000004482. Online ahead of print.

ABSTRACT

OBJECTIVE: Cerebrospinal fluid (CSF) β2-microglobulin (β2M) has not been fully characterized in people with HIV (PWH) in different categories of disease.

DESIGN: Retrospectively, we determined levels of β2M, 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: 1) neuroasymptomatic HIV (NA), 2) NA CSF escape, 3) symptomatic CSF escape, 4) secondary CSF escape, 5) HIV-associated dementia (HAD), 6) opportunistic infections in the central nervous system (CNS) (OI), and 7) 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 β2M levels were found in HAD, OI and symptomatic CSF escape. In 112 longitudinally followed NA participants, elevated CSF β2M levels (89%) were found at baseline, and (96%) for CSF neopterin. After ART initiation CSF β2M levels decreased by 10% per month and CSF neopterin by 17%. After three years 39% had CSF β2M and 44% had CSF neopterin levels above the reference values, similar to the controls (39%).

CONCLUSION: CSF β2M levels were elevated in the majority of individuals across HIV stages. Suppressive ART decreases β2M toward control levels, although neuroinflammation persists, most likely driven by non-HIV factors.

PMID:41789920 | DOI:10.1097/QAD.0000000000004482