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Anti-Human Immunodeficiency Virus Antibodies in the Cerebrospinal Fluid: Evidence of Early Treatment Impact on Central Nervous System Reservoir?

Journal article
Authors P. D. Burbelo
R. W. Price
Lars Hagberg
H. Hatano
S. Spudich
S. G. Deeks
Magnus Gisslén
Published in Journal of Infectious Diseases
Volume 217
Issue 7
Pages 1024-1032
ISSN 0022-1899
Publication year 2018
Published at Institute of Biomedicine, Department of Infectious Medicine
Pages 1024-1032
Language en
Keywords anti-retroviral therapy, antibodies, central nervous system, cerebrospinal fluid, early infection, HIV-1, persistence, serology
Subject categories Infectious Medicine

Abstract

Background Despite effective antiretroviral therapy (ART), human immunodeficiency virus (HIV) likely persists in the central nervous system (CNS) in treated individuals. We examined anti-HIV antibodies in cerebrospinal fluid (CSF) and blood as markers of persistence. Methods Human immunodeficiency virus antibodies were measured in paired CSF and serum before and after long-term treatment of chronic (n = 10) and early infection (n = 12), along with untreated early infection (n = 10). Results Treatment of chronic infection resulted in small reductions of anti-HIV antibodies in CSF and serum despite >10 years of suppressive ART. In untreated early infection, anti-HIV antibodies emerged in blood by day 30, whereas CSF antibodies reached similar levels 2 weeks later. Compared with long-term treatment of chronic infection, early ART initiation reduced CSF antibodies by 43-fold (P >.0001) and blood antibodies by 7-fold (P =.0003). Two individuals receiving pre-exposure prophylaxis and then ART early after infection failed to develop antibodies in CSF or blood, whereas CSF antibodies were markedly reduced in the Berlin patient. Conclusions To the extent that differential CSF and blood antibodies indicate HIV persistence, these data suggest a relative delay in establishment of the CNS compared with the systemic HIV reservoir that provides an opportunity for early treatment to have a greater impact on the magnitude of long-term CNS infection.

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