title: Cerebrospinal fluid HIV escape associated with progressive neurologic dysfunction in patients on antiretroviral therapy with well controlled plasma viral load.
abstract: OBJECTIVE
  To characterize HIV-infected patients with neurosymptomatic cerebrospinal fluid (CSF) 'escape', defined as detectable CSF HIV RNA in the setting of treatment-suppressed plasma levels or CSF RNA more than 1-log higher than plasma RNA.
  
  
  METHODS
  Retrospective case series.
  
  
  METHODS
  Four urban medical centers in the United States and Europe.
  
  
  METHODS
  Virologically controlled HIV-infected patients on antiretroviral therapy (ART) with progressive neurologic abnormalities who were determined to have CSF 'escape'. INTERVENTION Optimization of ART based upon drug susceptibility and presumed central nervous system exposure.
  
  
  METHODS
  Levels of CSF HIV RNA and inflammatory markers, clinical signs and symptoms, and MRI findings.
  
  
  RESULTS
  Ten patients presented with new neurologic abnormalities, which included sensory, motor, and cognitive manifestations. Median CSF HIV RNA was 3900 copies/ml (range 134-9056), whereas median plasma HIV RNA was 62 copies/ml (range <50 to 380). Median CD4 T-cell count was 482 cells/μl (range 290-660). All patients had been controlled to less than 500 copies/ml for median 27.5 months (range 2-96) and five of 10 had been suppressed to less than 50 copies/ml for median 19.5 months (range 2-96). Patients had documentation of a stable ART regimen for median 21 months (range 9-60). All had CSF pleocytosis or elevated CSF protein; seven of eight had abnormalities on MRI; and six of seven harbored CSF resistance mutations. Following optimization of ART, eight of nine patients improved clinically.
  
  
  CONCLUSIONS
  The development of neurologic symptoms in patients on ART with low or undetectable plasma HIV levels may be an indication of CSF 'escape'. This study adds to a growing body of literature regarding this rare condition in well controlled HIV infection.
authors.affiliation: Yale School of Medicine, New Haven, Connecticut, USA. michael.peluso@yale.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Peluso
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferretti
authors.forename: Julia
authors.initials: J
authors.lastname: Peterson
authors.forename: Evelyn
authors.initials: E
authors.lastname: Lee
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.forename: Antonio
authors.initials: A
authors.lastname: Boschini
authors.forename: Magnus
authors.initials: M
authors.lastname: Gisslén
authors.forename: Nancy
authors.initials: N
authors.lastname: Angoff
authors.forename: Richard W
authors.initials: RW
authors.lastname: Price
authors.forename: Paola
authors.initials: P
authors.lastname: Cinque
authors.forename: Serena
authors.initials: S
authors.lastname: Spudich
mesh_terms: D015526:AIDS Dementia Complex / Q000209:etiology / Q000503:physiopathology* / Q000821:virology; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D002490:Central Nervous System / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D018450:Disease Progression; D005060:Europe; D005260:Female; D006679:HIV Seropositivity / Q000150:complications / Q000503:physiopathology* / Q000821:virology; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000134:cerebrospinal fluid*; D012367:RNA, Viral / Q000187:drug effects; D012189:Retrospective Studies; D014481:United States; D014505:Urban Population; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D019798:Neopterin