title: Intrathecal viral replication and cerebral deficits in different stages of human immunodeficiency virus disease.
abstract: The objectives of this study is to clarify whether there are phases critical for the infection of the central nervous system (CNS) as defined by active viral replication in the cerebrospinal fluid (CSF) in human immunodeficiency virus (HIV) infection. One hundred and nine HIV-1-positive homo- and bisexual patients in early and late disease stages with or without highly active antiretroviral therapy (HAART) were included in the cross-sectional, diagnostic (phase I) multicenter study. No patients had any overt neurological deficits; all underwent venous and lumbar puncture as well as neuropsychological testing. In untreated early-stage patients, cerebrospinal fluid (CSF) viral load correlated with inflammatory parameters, but not significantly with neuropsychological abnormalities. CSF viral load and inflammatory reactions were suppressed in HAART-treated early-stage patients. In HAART-treated late-stage patients, there was a weak correlation between CSF viral load and CSF cell count as well as a moderate correlation with immune activation markers and with distinct cerebral deficits independent of CSF viral load. Seventeen of the 109 patients had higher CSF than plasma viral loads and marked inflammatory reactions and immune activation. In patients with greater plasma than CSF viral loads, the factors contributing to cerebral deficits still need to be identified. The results suggest not only that there is an early "set point" for CSF/central nervous system (CNS) infection, but also that there is a subgroup of patients in whom intrathecal viral replication correlates with cerebral deficits. Lumbar puncture should be performed in all positive patients to identify members of this subgroup and to ascertain what characteristic factors they have in common in order to improve therapy.
authors.affiliation: Department of Neurology, University Hospital of Dusseldorf (UKD), Dusseldorf, Germany. Gabriele.Arendt@uni-duesseldorf.de
authors.forename: Gabriele
authors.initials: G
authors.lastname: Arendt
authors.forename: Thorsten
authors.initials: T
authors.lastname: Nolting
authors.forename: Christian
authors.initials: C
authors.lastname: Frisch
authors.forename: Ingo-Wilhelm
authors.initials: IW
authors.lastname: Husstedt
authors.forename: Nora
authors.initials: N
authors.lastname: Gregor
authors.forename: Eleni
authors.initials: E
authors.lastname: Koutsilieri
authors.forename: Mattias
authors.initials: M
authors.lastname: Maschke
authors.forename: Alexander
authors.initials: A
authors.lastname: Angerer
authors.forename: Mark
authors.initials: M
authors.lastname: Obermann
authors.forename: Eva
authors.initials: E
authors.lastname: Neuen-Jacob
authors.forename: Ortwin
authors.initials: O
authors.lastname: Adams
authors.forename: Sabine
authors.initials: S
authors.lastname: Loeffert
authors.forename: Peter
authors.initials: P
authors.lastname: Riederer
authors.forename: Volker
authors.initials: V
authors.lastname: ter Meulen
authors.forename: Sieghart
authors.initials: S
authors.lastname: Sopper
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000821:virology*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D002555:Cerebrospinal Fluid / Q000821:virology*; D003072:Cognition Disorders / Q000175:diagnosis / Q000821:virology; D003430:Cross-Sectional Studies; D015497:HIV-1 / Q000254:growth & development* / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009483:Neuropsychological Tests; D019562:Viral Load; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents