Cognitive and Neuronal Link with Inflammation: A Longitudinal Study in People with and Without HIV Infection

Albert M. Anderson, Jeong Hoon Jang, Kirk A. Easley, Dietmar Fuchs, Magnus Gisslen, Henrik Zetterberg, Kaj Blennow, Ronald J. Ellis, Donald Franklin, Robert K. Heaton, Igor Grant, Scott L. Letendre

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Background: Across many settings, lack of virologic control remains common in people with HIV (PWH) because of late presentation and lack of retention in care. This contributes to neuronal damage and neurocognitive impairment, which remains prevalent. More evidence is needed to understand these outcomes in both PWH and people without HIV (PWOH).Methods: We recruited PWH initiating antiretroviral therapy and PWOH at 2 sites in the United States. One hundred eight adults were enrolled (56 PWOH and 52 PWH), most of whom had a second assessment at least 24 weeks later (193 total assessments). Tumor necrosis factor alpha, monocyte chemotactic protein-1 (MCP-1), neopterin, soluble CD14, and neurofilament light chain protein (NFL) were measured in plasma and cerebrospinal fluid (CSF). Using multivariate models including Bayesian model averaging, we analyzed factors associated with global neuropsychological performance (NPT-9) and CSF NFL at baseline and over time.Results: At baseline, higher CSF MCP-1 and plasma sCD14 were associated with worse NPT-9 in PWH, while CSF HIV RNA decrease was the only marker associated with improved NPT-9 over time. Among PWH, higher CSF neopterin was most closely associated with higher NFL. Among PWOH, higher CSF MCP-1 was most closely associated with higher NFL. After antiretroviral therapy initiation, decrease in CSF MCP-1 was most closely associated with NFL decrease.Conclusion: Monocyte-associated CSF biomarkers are highly associated with neuronal damage in both PWH and PWOH. More research is needed to evaluate whether therapies targeting monocyte-associated inflammation may ameliorate HIV-associated neurobehavioral diseases.

Original languageEnglish
Pages (from-to)617-625
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Issue number5
Publication statusPublished - 2020 Dec 15

Bibliographical note

Funding Information:
Study sponsorship: National Institutes of Health R21 MH085610 (principal investigator: S.L.L.), R01 MH058076 (principal investigator: R.J.E.), R01 MH107345 (coprincipal investigators: R.K.H. and S.L.L.), K23 MH095679, R21 MH118092, R01 AG062387 (principal investigator: A.M.A.), and K24 MH097673 (principal investigator: S.L.L.). The study was also supported by the Emory Center for AIDS Research (NIH P30AI050409). The study was also supported by grants from the Swedish and European Research Councils, Swedish State Support for Clinical Research (ALFGBG), the Knut and Alice Wallenberg Foundation, the Torsten Söderberg Foundation, P30AI050409 (Emory Center for AIDS Research), the Swedish Research Council (#2017-00915), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), and a grant (#ALFGBG-715986 and #ALFGBG-717531) from the Swedish state under the agreement between the Swedish government and the County Councils, the ALF agreement.

Publisher Copyright:
© 2020 Wolters Kluwer Health, Inc.

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Pharmacology (medical)


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