Asymptomatic Cerebrospinal Fluid HIV-1 Escape: Incidence and Consequences

Area of Science:

• Neurovirology
• Immunology
• Infectious Diseases

Background:

• Cerebrospinal fluid escape (CSFE) in people with HIV (PWH) on antiretroviral therapy (ART) is not well understood.
• The clinical significance of asymptomatic CSFE requires further investigation.

Purpose of the Study:

• To determine the incidence and impact of asymptomatic CSFE in a Swedish HIV cohort.
• To investigate the association between asymptomatic CSFE and biomarkers of central nervous system (CNS) inflammation and injury.

Main Methods:

• Longitudinal follow-up of neuroasymptomatic PWH on ART with suppressed viral load.
• Definition of CSFE: elevated CSF HIV-1 RNA with suppressed plasma viral load or higher CSF than plasma HIV-1 RNA.
• Analysis of paired CSF and plasma for HIV-1 RNA, neopterin, neurofilament light protein (NfL), white blood cell (WBC) count, and albumin ratio.

Main Results:

• Asymptomatic CSFE was detected in 2% of PWH (4/173) and 1% of samples (5/449) using a cutoff of 50 copies/mL.
• Using a 20 copies/mL cutoff, CSFE was found in 8% of PWH and 4% of samples.
• CSFE samples showed increased CSF neopterin and albumin ratio, indicating CNS immune activation and blood-brain barrier impairment.
• Elevated CSF WBC count was significantly associated with CSFE (OR 3.9, P = .004).

Conclusions:

• Asymptomatic CSFE is uncommon in PWH on effective ART, with no continuous cases observed.
• Increased CSF HIV-1 RNA during ART is linked to CNS immune activation and blood-brain barrier dysfunction.
• Biomarkers of neuronal injury (NfL) were not associated with asymptomatic CSFE.