Background
HIV-1 invades the central nervous system (CNS) during acute infection and thereafter persists in the CNS. This leads to chronic intrathecal immune activation which can be measured by various biomarkers in cerebrospinal fluid (CSF). β2-microglobulin (β2M) is a marker of cellular immune activation that has previously been studied in CSF in people with HIV (PWH), but mainly in smaller cohorts. The aim of this study was to describe CSF β2M levels in a large cohort of PWH.
Methods
In this retrospective study, 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 ART. Participants were divided into seven groups: 1) neuroasymptomatic HIV (NA), 2) NA CSF escape, 3) symptomatic CSF escape, 4) secondary CSF escape, 5) HIV-associated dementia (HAD), 6) opportunistic CNS infections (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); CNS OI (N = 18); and elite controllers (N = 6). In addition, 59 HIV negative controls were included. Highest CSF β2M levels were found in HAD and symptomatic CSF escape (figure 1). In 112 longitudinally followed NA participants, increased CSF β2M levels (90%) were found at baseline, compared with 96% for CSF neopterin. After initiation of ART CSF β2M levels decreased by 9% per month and CSF neopterin with 16%. Still, 68% had CSF β2M and 80% had CSF neopterin levels above the reference values after six months.
Conclusions
In this extensive cohort of PWH with various stages of disease, CSF β2M was shown to be a robust marker of intrathecal inflammation, with the highest levels found in HAD and in symptomatic CSF escape. ART decreases β2M levels, but, 68 % still had increased levels after six months, despite having achieved viral suppression.
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