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Cognitive Phenotypes of HIV Defined Using a Novel Data-driven Approach

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Abstract

The current study applied data-driven methods to identify and explain novel cognitive phenotypes of HIV. Methods: 388 people with HIV (PWH) with an average age of 46 (15.8) and median plasma CD4+ T-cell count of 555 copies/mL (79% virally suppressed) underwent cognitive testing and 3T neuroimaging. Demographics, HIV disease variables, and health comorbidities were recorded within three months of cognitive testing/neuroimaging. Hierarchical clustering was employed to identify cognitive phenotypes followed by ensemble machine learning to delineate the features that determined membership in the cognitive phenotypes. Hierarchical clustering identified five cognitive phenotypes. Cluster 1 (n=97) was comprised of individuals with normative performance on all cognitive tests. The remaining clusters were defined by impairment on action fluency (Cluster 2; n=46); verbal learning/memory (Cluster 3; n=73); action fluency and verbal learning/memory (Cluster 4; n=56); and action fluency, verbal learning/memory, and tests of executive function (Cluster 5; n=114). HIV detectability was most common in Cluster 5. Machine learning revealed that polysubstance use, race, educational attainment, and volumes of the precuneus, cingulate, nucleus accumbens, and thalamus differentiated membership in the normal vs. impaired clusters. The determinants of persistent cognitive impairment among PWH receiving suppressive treatment are multifactorial nature. Viral replication after ART plays a role in the causal pathway, but psychosocial factors (race inequities, substance use) merit increased attention as critical determinants of cognitive impairment in the context of ART. Results underscore the need for comprehensive person-centered interventions that go beyond adherence to patient care to achieve optimal cognitive health among PWH.

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Funding

BA received funding from the National Institute of Mental Health (R01MH118031; K23MH08175) and National Institute of Nursing Research (R01NR015738; R01NR012907; R01NR012657; R01NR014449) and National Institute of Drug Abuse (R01DA054009). RP received funding from the National Institute of Mental Health (R01MH113560).

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Authors and Affiliations

  1. Department of Psychological Sciences, University of Missouri Saint Louis, Missouri, Saint Louis, US

    Robert H. Paul

  2. Missouri Institute of Mental Health, University of Missouri Saint Louis, Missouri, Saint Louis, US

    Robert H. Paul, Kyu Cho, Andrew Belden, Jacob Bolzenius & Julie Mannarino

  3. Department of Public Health, University of Miami School of Medicine, Coral Gables, Florida, US

    Adam W. Carrico

  4. Department of Psychiatry, Rush University School of Medicine, Chicago, Illinois, US

    Eileen Martin

  5. Department of Neurology, Washington University, Saint Louis, Missouri, US

    Patrick Luckett, Sarah A. Cooley & Beau M. Ances

  6. Center for Addiction Medicine, Harvard Medical School/Massachusetts General Hospital, Boston, Massachusetts, US

    Jodi M. Gilman

  7. Department of Communication Sciences and Disorders, Northern Arizona University, Flagstaff, Arizona, US

    Mariah Miano

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  1. Robert H. Paul
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  2. Kyu Cho
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  3. Andrew Belden
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Correspondence to Robert H. Paul.

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Paul, R.H., Cho, K., Belden, A. et al. Cognitive Phenotypes of HIV Defined Using a Novel Data-driven Approach. J Neuroimmune Pharmacol 17, 515–525 (2022). https://doi.org/10.1007/s11481-021-10045-0

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