Cerebrospinal fluid virology in people with HIV

Abstract

Objective Our objectives were to investigate the recent frequency of cerebrospinal fluid (CSF) HIV RNA escape and other CSF viral nucleic acid detection in people with HIV with neurological symptoms and to assess associated clinical factors. Method This was a retrospective cohort analysis of people with HIV who underwent CSF examination for clinical indications between 2017 and 2022. Individuals were identified from pathology records, and clinical data were recorded. CSF HIV RNA escape was defined as CSF HIV RNA concentrations greater than in plasma. CSF viral screen included herpes simplex virus types 1 (HSV‐1) and 2 (HSV‐2), varicella zoster virus (VZV), Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV‐6) and JC virus. When cases were detected in five or more people with HIV, associated clinical factors were assessed using linear regression modelling. Results CSF HIV RNA escape was observed in 19 of 114 individuals (17%) and was associated with the presence of HIV drug resistance mutations and non‐integrase strand transfer inhibitor‐based antiretroviral therapy (p < 0.05 for all) when compared to people with HIV without escape. Positive viral nucleic acid testing included EBV (n = 10), VZV (3), CMV (2), HHV‐6 (2) and JC virus (4). Detectable CSF EBV was not considered related to neurological symptoms and was associated with concomitant CSF infections in eight of ten individuals and with CSF pleocytosis, previous AIDS, lower nadir and current CD4 T‐cell count (p < 0.05 for all). Conclusion In people with HIV with neurological symptoms, the frequency of CSF HIV RNA escape remains similar to that in historical reports. Detectable EBV viral nucleic acid in the CSF was observed frequently and, in the absence of clinical manifestations, may be a consequence of CSF pleocytosis.

Cerebrospinal fluid pleocytosis is associated with HIV-1 neuroinvasion during acute infection

“…More research is needed to see if our data is applicable to a broader population. BBB permeability was not characterized through measurements of CSF and plasma albumin and the co-infection list was not exhaustive to evaluate other pathogens’ effects on CSF pleocytosis [ 15 ]. As almost all RV254 participants commenced antiretroviral therapy (ART) within days after study enrolment, it is impossible to conclude from our data whether CSF pleocytosis will inevitably occur shortly after AHI and whether early CSF pleocytosis during AHI would alter the natural course of HIV-1 compartmentalization in the CNS and its neuropathogenesis.…”

Is the Central Nervous System Reservoir a Hurdle for an HIV Cure?

“…The discordance between plasma and CSF viral load is attributed to the compartmentalization of HIV in the CNS with associated presumed HIV egress from the CNS tissues into the CSF. The incidence of CSF escape has been reported in between 4-17% of adults receiving ART [116][117][118][119]. Pérez-Valero and colleagues assessed 1264 PWH who were on stable ART for more than six months with plasma viral loads <50 copies/mL.…”

“…The plasma and CSF viral RNA levels were measured between 2003 and 2011 and HIV CSF escape was reported in 4.4% of the participants [117]. In a recent study with 114 PWH receiving suppressive ART that had CSF examination between 2017 and 2022, the viral escape was estimated at 17% [118]. Besides HIV, CSF viral load for EBV, VZV, CMV, HHV-6, and JC virus was quantified, revealing EBV-encoded nucleic acid detection in 9% of the cohort, which was ascribed to HIV infection-induced CSF pleocytosis although it was unclear whether EBV and HIV CSF escape were temporally concurrent [118].…”

“…In a recent study with 114 PWH receiving suppressive ART that had CSF examination between 2017 and 2022, the viral escape was estimated at 17% [118]. Besides HIV, CSF viral load for EBV, VZV, CMV, HHV-6, and JC virus was quantified, revealing EBV-encoded nucleic acid detection in 9% of the cohort, which was ascribed to HIV infection-induced CSF pleocytosis although it was unclear whether EBV and HIV CSF escape were temporally concurrent [118]. Filippidis and colleagues assessed 288 PWH who underwent lumbar puncture between 2011 and 2019 and detected HIV escape in 6.5% of the participants who had suppressed plasma viral RNA levels [119].…”

“…Low-level persistence of plasma viremia during ART is another potential contributor to the presence of drug-resistant viral variants in the CSF [122][123][124]. The impact of CSF escape on neurocognitive performance remains uncertain; some groups have associated the presence of HIV in the CSF with neurocognitive decline [49,120,125,126], although these associations were not confirmed by other studies [117][118][119]. Another unknown aspect of HIV CSF escape is whether the escaped virus can contribute to systemic rebound infection, or merely prompt transient plasma viral elevations (termed 'blips') that can resolve with adherence to the prescribed ART regimen.…”