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

Artikel i vetenskaplig tidskrift
Författare M. J. Peluso
F. Ferretti
J. Peterson
E. Lee
D. Fuchs
A. Boschini
Magnus Gisslén
N. Angoff
R. W. Price
P. Cinque
S. Spudich
Publicerad i Aids
Volym 26
Nummer/häfte 14
Sidor 1765-1774
ISSN 0269-9370
Publiceringsår 2012
Publicerad vid Institutionen för biomedicin, avdelningen för infektionssjukdomar
Sidor 1765-1774
Språk en
Länkar dx.doi.org/10.1097/QAD.0b013e328355...
Ämnesord antiretroviral therapy, central nervous system, cerebrospinal fluid, HIV, HIV drug resistance, HIV, human-immunodeficiency-virus, reverse-transcriptase sequence, neurocognitive disorders, type-1, infection, resistance, neopterin, dementia, encephalitis, replication
Ämneskategorier Immunologi inom det medicinska området

Sammanfattning

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/mu l (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. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

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