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Limited correlation between systemic biomarkers and neurocognitive performance before and during HIV treatment

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Abstract

The AIDS Clinical Trials Group (ACTG) study A5303 investigated the associations between neuropsychological performance (NP) and inflammatory biomarkers in HIV-infected participants. Fifteen NP tests were administered at baseline and week 48 to 233 ART naïve participants randomized to maraviroc- or tenofovir-containing ART. Neurocognition correlated modestly with markers of lymphocyte activation and inflammation pre-ART (percent CD38+/HLA-DR+(CD4+) (r = − 0.22, p = 0.02) and percent CD38+/HLA-DR+(CD8+) (r = − 0.25, p = 0.02)), and with some monocyte subsets during ART (r = 0.25, p = 0.02). Higher interleukin-6 and percent CD38+/HLA-DR+(CD8+) were independently associated with worse severity of HIV-associated neurocognitive disorders (HAND) (p = 0.04 and 0.01, respectively). More studies to identify HAND biomarkers are needed.

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Acknowledgments

We acknowledge members of the ACTG A5303 team: Denise Barr (clinical trials specialist), Ana I. Martinez (DAIDS pharmacist), Robert Kalayjian and Cara Wilson (investigators), Edward Acosta (pharmacologist), David Rusin (data manager), Amy Gonzales (laboratory data manager), Orlando Roman (community representative), Kathy Melbourne (Gilead), James Rooney (Gilead), Alex Reinhart (ViiV), Bryan Baugh (Janssen), Roula Qaqish (Abbvie), Heera R Jayvant (Pfizer), and Laura Napolitano, Charles Walworth, Christos Petropoulos (Labcorp). We gratefully acknowledge the research sites and personnel who participated in this study: Ohio State University (John Davis, Mark Hite); UCSD Antiviral Research Center (Edward Seefried, Constance Benson); Northwestern University (Nina Lambert, Karen Coleman); University of Alabama (Messer, Tamara James); University of Cincinnati (Amy Dill, Jenifer Baer); University of Colorado Hospital (Christine Griesmer, Cathi Basler); University of Miami (Hector Bolivar, Margaret A Fischl); Houston AIDS Research Team (Roberto C Arduino, Aristoteles E Villamil); Rush University (Beverly Sha, Tondria Green); Vanderbilt University (Brenda Jackson, Fred Nicotera); Washington University in St Louis (GeYoul Kim, Mark Rodrieguez); University of California, San Francisco (Annie Luetkemeyer, Jay Dwyer); The Miriam Hospital (Pamela Poethke, Aadia Rana); University of Carolina, Chapel-Hill (Miriam Chicurel-Bayard, Megan Telfer); University of Carolina Greensboro research site (Cornelius van Dam, Timothy Lane); Ponce de Leon Center Emory University (Ighovwerha Ofotokun, Melody Palmore); Case Western University (Patricia Walton, Felicia Williams); Puerto Rico Clinical Trials Unit (Jorge L. Santana, Olga I. Mendez); University of Pennsylvania (Pablo Tebas, Aleshia Thomas); Massachusetts General Hospital (Teri Flynn, ANP-BC, Amy Sbrolla); UCLA CARE Center (Raphael Landovitz, Vanessa Cajahuaringa); University of Washington AIDS CRS (Shelia Dunaway, Sheryl Storey); Johns Hopkins University (Ilene Wiggins, Andrea Weiss); University of Colorado (Daniel Reirden, Hannah Bernath); Columbia Physicians and Surgeons (Michael Yin, Jolene Noel-Connor); Cooper University Hospital (Rose Kim, Yolanda Smith); Brigham and Women’s Hospital (Paul Sax, Cheryl Keenan); Georgetown University (Princy Kumar, Joseph Timpone); University of Southern California (Michael P Dubé, Bartolo Santos); University of Rochester (Mary Adams, Christine Hurley). Finally, we thank all the patients who volunteered for the study.

Funding

This research was supported by Award Number U01AI068636 from the National Institute of Allergy and Infectious Diseases and supported by National Institute of Mental Health (NIMH), National Institute of Dental and Craniofacial Research (NIDCR). This work was also supported by other grants from the National Institute of Health AI068634 and AI068636 to ACTG Statistical Data Analysis Center and to the research sites that participated in the study.

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Authors and Affiliations

  1. Department of Neurology, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA

    Kevin Robertson & Alyssa Vecchio

  2. Department of Microbial Pathogens and Immunity, Rush Medical College, Chicago, IL, USA

    Alan Landay

  3. Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Sachiko Miyahara

  4. Division of Infectious Diseases, Northwestern Univeristy, 645 N. Michigan Avenue, Suite 900, Chicago, IL, 60611, USA

    Mary Clare Masters & Babafemi O. Taiwo

  5. Departmet of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Todd T. Brown

Authors
  1. Kevin Robertson
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  2. Alan Landay
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  4. Alyssa Vecchio
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  7. Babafemi O. Taiwo
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Corresponding author

Correspondence to Babafemi O. Taiwo.

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Conflict of interest

A.L. has served on the scientific advisory board for Merck and has provided scientific consultation to GlaxoSmithKline, Bristol-Myers Squibb, and Tobira.

T.T. B. as served as a consultant for Bristol-Myers Squibb, GlaxoSmithKline, Merck, AbbVie, Gilead, ViiV, Theratechnologies, and EMD-Serono and has received research funding from Merck and GlaxoSmithKline.

B.O.T. has served as a consultant to ViiV, Pfizer, Janssen, GlaxoSmithKline, and Gilead, and received research support to Northwestern University from ViiV and Pfizer.

All other authors declared no conflicts of interest.

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Robertson, K., Landay, A., Miyahara, S. et al. Limited correlation between systemic biomarkers and neurocognitive performance before and during HIV treatment. J. Neurovirol. 26, 107–113 (2020). https://doi.org/10.1007/s13365-019-00795-2

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