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. 2017 Feb;23(1):106-112.
doi: 10.1007/s13365-016-0466-z. Epub 2016 Jul 11.

Cerebrospinal fluid interferon alpha levels correlate with neurocognitive impairment in ambulatory HIV-Infected individuals

Albert M Anderson  1 , Jeffrey L Lennox  2 , Mark M Mulligan  2 , David W Loring  3 , Henrik Zetterberg  4   5 , Kaj Blennow  4 , Cari Kessing  6 , Rajeth Koneru  3 , Kirk Easley  7 , William R Tyor  3   8
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Cerebrospinal fluid interferon alpha levels correlate with neurocognitive impairment in ambulatory HIV-Infected individuals

Albert M Anderson et al. J Neurovirol. 2017 Feb.

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.

Keywords: Aids; HIV; Interferon alpha; Memory disorders.

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Conflict of interest statement

Conflict of Interest Statement: The authors declare that they have no conflict of interest

Figures

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Figure 2
Figure 2
Linear regression relationship between CSF IFNα and NPT-8 with 95% confidence interval in shaded blue
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