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Low levels of HIV-1 RNA detected in the cerebrospinal fluid after up to 10 years of suppressive therapy are associated with local immune activation

Journal article
Authors V. Dahl
J. Peterson
D. Fuchs
Magnus Gisslén
S. Palmer
R. W. Price
Published in Aids
Volume 28
Issue 15
Pages 2251-2258
ISSN 0269-9370
Publication year 2014
Published at Institute of Biomedicine, Department of Infectious Medicine
Pages 2251-2258
Language en
Links dx.doi.org/10.1097/qad.000000000000...
Keywords central nervous system, cerebrospinal fluid, HIV, immune, inflammation, neurological, reservoir, CENTRAL-NERVOUS-SYSTEM, ACTIVE ANTIRETROVIRAL THERAPY, AIDS DEMENTIA, COMPLEX, TREATMENT INTENSIFICATION, NEUROCOGNITIVE DISORDERS, INFECTION, ERA, PLASMA, IMMUNOACTIVATION, IMPAIRMENT, Immunology, Infectious Diseases, Virology
Subject categories Immunology in the medical area

Abstract

Objective and design:Though combination antiretroviral therapy reduces the concentration of HIV-1 RNA in both plasma and cerebrospinal fluid (CSF) below the detection limit of clinical assays, low levels of HIV-1 RNA are frequently detectable in plasma using more sensitive assays. We examined the frequency and magnitude of persistent low-level HIV-1 RNA in CSF and its relation to the central nervous system (CNS) immune activation.Methods:CSF and plasma HIV-1 RNA were measured using the single-copy assay with a detection limit of 0.3 copies/ml in 70 CSF and 68 plasma samples from 45 treated HIV-1-infected patients with less than 40 copies/ml of HIV-1 RNA in both fluids by standard clinical assays. We also measured CSF neopterin to assess intrathecal immune activation. Theoretical drug exposure was estimated using the CNS penetration-efficacy score of treatment regimens.Results:CSF HIV-1 RNA was detected in 12 of the 70 CSF samples (17%) taken after up to 10 years of suppressive therapy, compared to 39 of the 68 plasma samples (57%) with a median concentration of less than 0.3 copies/ml in CSF compared to 0.3 copies/ml in plasma (P<0.0001). CSF samples with detectable HIV-1 RNA had higher CSF neopterin levels (mean 8.2 compared to 5.7nmol/l; P=0.0085). Patients with detectable HIV-1 RNA in CSF did not differ in pretreatment plasma HIV-1 RNA levels, nadir CD4(+) cell count or CNS penetration-efficacy score.Conclusion:Low-level CSF HIV-1 RNA and its association with elevated CSF neopterin highlight the potential for the CNS to serve as a viral reservoir and for persistent infection to cause subclinical CNS injury.

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