Asymptomatic Cerebrospinal Fluid HIV-1 Escape: Incidence and Consequences

Background. The incidence and clinical relevance of asymptomatic cerebrospinal fluid escape (CSFE) during antiretroviral therapy (ART) is uncertain. We examined the impact and incidence of asymptomatic CSFE in a Swedish HIV cohort. Methods. Neuroasymptomatic people with HIV (PWH) who have been on ART for at least 6 months with suppressed plasma viral load were followed longitudinally. CSFE was defined as either increased CSF HIV-1 RNA with concurrent plasma suppression or CSF HIV-1 RNA exceeding that in plasma when both were quantifiable. Paired CSF and plasma were analyzed for HIV-1 RNA, neopterin, neurofilament light protein (NfL), white blood cell (WBC) count, and albumin ratio. Results. Asymptomatic CSFE (cutoff 50 copies/mL) was found in 4 of 173 PWH (2%) and 5 of 449 samples (1%). The corresponding proportions were 8% of PWH and 4% for samples using a 20 copies/mL cutoff for CSF HIV-1 RNA. CSFE samples (cutoff 20 copies/mL) had a 25% higher geometric mean of CSF neopterin (P = .01) and 8% higher albumin ratio (P = .04) compared to samples without CSFE. No differences were observed in CSF NfL levels (P = .8). The odds ratio for increased CSF WBC (>= 3 cells/mu L) in samples with CSFE was 3.9 (P = .004), compared to samples without elevated CSF viral load. Conclusions. Asymptomatic CSFE was identified in only 4 (2%) PWH, with no cases of continuous CSFE observed. Increased CSF HIV-1 RNA was associated with biomarkers of CNS immune activation and blood-brain barrier impairment, but not with biomarkers of neuronal injury.