title: Cerebrospinal fluid interferon alpha levels correlate with neurocognitive impairment in ambulatory HIV-Infected individuals.
abstract: HIV-associated neurocognitive disorders (HANDs) continue to be common and are associated with increased morbidity and mortality. However, the underlying mechanisms in the combination antiretroviral therapy (cART) era are not fully understood. Interferon alpha (IFNα) is an antiviral cytokine found to be elevated in the cerebrospinal fluid (CSF) of individuals with advanced HIV-associated dementia in the pre-cART era. In this cross-sectional study, we investigated the association between IFNα and neurocognitive performance in ambulatory HIV-infected individuals with milder impairment. An eight-test neuropsychological battery representing six cognitive domains was administered. Individual scores were adjusted for demographic characteristics, and a composite neuropsychological score (NPT-8) was calculated. IFNα and CSF neurofilament light chain (NFL) levels were measured using enzyme-linked immunosorbent assay (ELISA). There were 15 chronically infected participants with a history of significant immunocompromise (median nadir CD4+ of 49 cells/μl). Most participants were neurocognitively impaired (mean global deficit score of 0.86). CSF IFNα negatively correlated with three individual tests (Trailmaking A, Trailmaking B, and Stroop Color-Word) as well as the composite NPT-8 score (r = -0.67, p = 0.006). These negative correlations persisted in multivariable analyses adjusting for chronic hepatitis B and C. Additionally, CSF IFNα correlated strongly with CSF NFL, a marker of neuronal damage (rho = 0.748, p = 0.0013). These results extend findings from individuals with severe HIV-associated dementia in the pre-cART era and suggest that IFNα may continue to play a role in HAND pathogenesis during the cART era. Further investigation into the role of IFNα is indicated.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, 341 Ponce de Leon Avenue, Atlanta, GA, 30308, USA. aande2@emory.edu.
authors.forename: Albert M
authors.initials: AM
authors.lastname: Anderson
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, 341 Ponce de Leon Avenue, Atlanta, GA, 30308, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Lennox
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, 341 Ponce de Leon Avenue, Atlanta, GA, 30308, USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Mulligan
authors.affiliation: Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Loring
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mӧlndal, Sweden.|Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mӧlndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, Jupiter, FL, USA.
authors.forename: Cari
authors.initials: C
authors.lastname: Kessing
authors.affiliation: Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Rajeth
authors.initials: R
authors.lastname: Koneru
authors.affiliation: Department of Biostatistics, Emory University Rollins School of Public Health, Atlanta, GA, USA.
authors.forename: Kirk
authors.initials: K
authors.lastname: Easley
authors.affiliation: Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.|Atlanta Veterans Affairs Medical Center, Decatur, GA, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Tyor
mesh_terms: D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D003071:Cognition / Q000502:physiology; D003430:Cross-Sectional Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D016867:Immunocompromised Host; D016898:Interferon-alpha / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000276:immunology; D009483:Neuropsychological Tests; D010045:Outpatients
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D016900:Neurofilament Proteins; C044882:neurofilament protein L
keywords: Aids; HIV; Interferon alpha; Memory disorders