Rapid decline of cerebrospinal fluid biomarkers of axonal injury and neuroinflammation after initiation of antiretroviral therapy in HIV

Persistent intrathecal immune activation and neuronal injury remain common in people with HIV (PWH) despite effective antiretroviral therapy (ART). We examined longitudinal trajectories of cerebrospinal fluid (CSF) neurofilament light (NfL), a marker of axonal injury, together with neuroinflammatory biomarkers following ART initiation. Ninety-nine PWH from the Gothenburg HIV CSF Study Cohort who achieved viral suppression were included, with CSF samples collected before and after treatment initiation. NfL and a panel of biomarkers including YKL-40, sTREM-2, neopterin, and GFAP were analyzed. CSF NfL declined rapidly, from a mean of 673 ng/L at baseline to 592 ng/L after three months and 490 ng/L after twelve months. All inflammatory biomarkers showed parallel and significant decreases. Prior to ART, 25% of participants had elevated NfL levels; this subgroup displayed higher baseline inflammation, and the steepest biomarker declines after treatment initiation. In participants with normal baseline NfL, inflammatory markers decreased while NfL remained stable. Beyond one year, no further reductions were evident. These longitudinal findings demonstrate that ART rapidly and effectively reduces CSF biomarkers of neuronal injury and neuroinflammation in HIV, with the greatest benefit in individuals with baseline axonal damage.