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Components of metabolic syndrome associated with lower neurocognitive performance in youth with perinatally acquired HIV and youth who are HIV-exposed uninfected

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Abstract

We investigated the association of metabolic syndrome (MetS) and its components [abdominal obesity, elevated triglycerides (TG), low HDL cholesterol, elevated blood pressure (BP), and impaired fasting glycemia (IFG)] with neurocognitive impairment in youth with perinatally acquired HIV (YPHIV) or who are perinatally HIV-exposed uninfected (YPHEU). This was an observational study with a comparison group of 350 YPHIV and 68 YPHEU ages 10–19 years. Youth with MetS components measured between 1 year before and 3 months after a baseline neurocognitive assessment (Wechsler Intelligence Scale) were selected from the Pediatric HIV/AIDS Cohort Study (PHACS). A sub-group completed another assessment 3 years later. We assessed the association of each baseline MetS component with five standardized neurocognitive indices at baseline and changes in indices over time. At baseline, 15% of YPHIV and 18% of YPHEU met criteria for ≥ 2 MetS components. Among YPHIV, there was no association between MetS components and neurocognitive indices at baseline; however, over time, elevated baseline BP was associated with a greater decrease in mean Perceptual Reasoning scores (−4.3;95%CI: −8.8,0.3) and ≥ 2 MetS components with a greater decrease in mean Processing Speed scores (−5.1;95%CI: −9.4, −0.8). Among YPHEU, elevated TG was associated with lower mean Verbal Comprehension, Perceptual Reasoning, and Full-scale IQ scores at baseline, and IFG with lower mean Verbal Comprehension scores. Components of MetS in YPHIV (elevated BP) and YPHEU (elevated TG and IFG) were associated with lower neurocognitive performance index scores. Studies to elucidate how modifying metabolic risk factors early in life may improve neurocognitive outcomes in this population are warranted.

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Data availability and code availability

Data management services were provided by Frontier Science and Technology Research Foundation (PI: Suzanne Siminski), and regulatory services and logistical support were provided by Westat, Inc (PI: Julie Davidson).

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Acknowledgements

We thank the participants and families for their participation in PHACS, and the individuals and institutions involved in the conduct of PHACS. The following institutions, clinical site investigators, and staff participated in conducting PHACS AMP and AMP Up in 2019, in alphabetical order: Ann and Robert H. Lurie Children’s Hospital of Chicago: Ellen Chadwick, Margaret Ann Sanders, Kathleen Malee, Yoonsun Pyun; Baylor College of Medicine:, Mary Paul, Shelley Buschur, Chivon McMullen-Jackson, Lynnette Harris; Bronx Lebanon Hospital Center: Murli Purswani, Mahboobullah Mirza Baig, Alma Villegas; Children’s Diagnostic & Treatment Center: Lisa- Gaye Robinson, Sandra Navarro, Patricia Garvie; Boston Children’s Hospital: Sandra K. Burchett, Rebecca Pinsky, Adam R. Cassidy; Jacobi Medical Center: Andrew Wiznia, Marlene Burey, Ray Shaw; Rutgers—New Jersey Medical School: Arry Dieudonne, Linda Bettica, Juliette Johnson, Karen Surowiec; St. Christopher’s Hospital for Children: Janet S. Chen, Taesha White, Mitzie Grant; St. Jude Children’s Research Hospital: Katherine Knapp, Jamie Russell-Bell, Megan Wilkins, Erick Odero; San Juan Hospital Research Unit/Department of Pediatrics, San Juan Puerto Rico: Midnela Acevedo-Flores, Heida Rios, Vivian Olivera; Tulane University School of Medicine: Margarita Silio, Medea Gabriel, Patricia Sirois; University of California, San Diego: Stephen A. Spector, Megan Loughran, Veronica Figueroa, Sharon Nichols; University of Colorado Denver Health Sciences Center: Elizabeth McFarland, Carrie Chambers, Emily Barr, Mary Glidden; University of Miami: Gwendolyn Scott, Grace Alvarez, Juan Caffroni, Anai Cuadra.

Funding

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with co-funding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Institute of Dental and Craniofacial Research, the National Cancer Institute, the National Institute on Alcohol Abuse and Alcoholism, the Office of AIDS Research, and the National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health (HD052102) (Principal Investigator: George R Seage III; Program Director: Liz Salomon) and the Tulane University School of Medicine (HD052104) (Principal Investigator: Russell Van Dyke; Co-Principal Investigator: Ellen Chadwick; Project Director: Patrick Davis).

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Authors and Affiliations

  1. Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA

    Stephanie Shiau

  2. Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Wendy Yu & Denise L. Jacobson

  3. Department of Neurosciences, University of California, La Jolla, San Diego, CA, USA

    Sharon Nichols

  4. Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA

    Elizabeth J. McFarland

  5. Department of Pediatrics, Drexel University College of Medicine, Philadelphia, PA, USA

    Janet S. Chen

  6. University Hospitals Cleveland Medical Center, Rainbow Babies and Children’s Hospital, Case Western Reserve University, Cleveland, OH, USA

    Sahera Dirajlal-Fargo

  7. Department of Pediatrics, New Jersey Medical School, Newark, NJ, USA

    Karen Surowiec

  8. The Saban Research Institute, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    Mitchell E. Geffner

  9. Department of Pediatrics, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Jennifer Jao

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  1. Stephanie Shiau
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  2. Wendy Yu
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Pediatric HIV/AIDS Cohort Study

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Correspondence to Stephanie Shiau.

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Competing interests

Chen: J.S.C. receives research support paid to institution from Gilead Sciences, Inc. Geffner: M.E.G. receives research support from Novo Nordisk; consultant fees from Adrenas, Daiichi Sankyo, Eton Pharmaceuticals, Neurocrine Biosciences, Novo Nordisk, Pfizer, and QED; and royalties from McGraw-Hill and UpToDate; and serves on a data safety monitoring board for Ascendis. All other authors declare no competing interests.

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Shiau, S., Yu, W., Jacobson, D.L. et al. Components of metabolic syndrome associated with lower neurocognitive performance in youth with perinatally acquired HIV and youth who are HIV-exposed uninfected. J. Neurovirol. 27, 702–715 (2021). https://doi.org/10.1007/s13365-021-01005-8

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