Cerebrospinal fluid HIV escape associated with progressive neurologic dysfunction in patients on antiretroviral therapy with well controlled plasma viral load


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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.Design:Retrospective case series.Setting:Four urban medical centers in the United States and Europe.Participants: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.Main outcome measures: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.Conclusion: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.

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