Comprehensive study of cerebrospinal fluid β 2 -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.