Neurocognitive Dysfunction With Neuronal Injury in People With HIV on Long-Duration Antiretroviral Therapy

Authors

Cynthia McMahan
Devon K Dietrich
Elizabeth F Horne
Erin Kelly
Katrina Geannopoulos
Peter Selim Siyahhan Julnes
Lillian Ham
Ulisses Santamaria
Chuen-Yen Lau
Tianxia Wu
Hsing-Chuan Hsieh
Anuradha Ganesan
Catherine Berjohn
Suad Kapetanovic
Daniel S Reich
Govind Nair
Joseph Snow
Brian K Agan
Avindra Nath
Bryan R Smith

Language

English

Publication Date

6-13-2023

Journal

Neurology

DOI

10.1212/WNL.0000000000207339

PMID

37105760

PMCID

PMC10264056

PubMedCentral® Posted Date

6-13-2023

PubMedCentral® Full Text Version

Post-print

Abstract

Background and objectives: Neurologic outcomes in people with HIV (PWH) on long-duration antiretroviral therapy (ART) are not fully understood, and the underlying pathophysiology is unclear. To address this, we established a cohort of such individuals and compared them with HIV-negative controls using a novel matching technique. Both groups underwent extensive cognitive testing, evaluation for psychiatric measures, and MRI and CSF analyses.

Methods: Participants underwent comprehensive neuropsychological testing and completed standardized questionnaires measuring depressive symptoms, perceptions of own functioning, and activities of daily living as part of an observational study. Brain MRI and lumbar puncture were optional. Coarsened Exact Matching was used to reduce between-group differences in age and sex, and weighted linear/logistic regression models were used to assess the effect of HIV on outcomes.

Results: Data were analyzed from 155 PWH on ART for at least 15 years and 100 HIV-negative controls. Compared with controls, PWH scored lower in the domains of attention/working memory (PWH least square mean [LSM] = 50.4 vs controls LSM = 53.1, p = 0.008) and motor function (44.6 vs 47.7, p = 0.009) and a test of information processing speed (symbol search 30.3 vs 32.2, p = 0.003). They were more likely to self-report a higher number of cognitive difficulties in everyday life (p = 0.011). PWH also reported more depressive symptoms, general anxiety, and use of psychiatric medications (all with p < 0.05). PWH had reduced proportions of subcortical gray matter on MRI (β = -0.001, p < 0.001), and CSF showed elevated levels of neurofilament light chain (664 vs 529 pg/mL, p = 0.01) and tumor necrosis factor α (0.229 vs 0.156 ng/mL, p = 0.0008).

Discussion: PWH, despite effective ART for over a decade, displayed neurocognitive deficits and mood abnormalities. MRI and CSF analyses revealed reduced brain volume and signs of ongoing neuronal injury and neuroinflammation. As the already large proportion of virologically controlled PWH continues to grow, longitudinal studies should be conducted to elucidate the implications of cognitive, psychiatric, MRI, and CSF abnormalities in this group.

Keywords

Humans, Activities of Daily Living, HIV Infections, Cognitive Dysfunction, Cognition, Memory, Short-Term

Published Open-Access

yes

Recommended Citation

McMahan, Cynthia; Dietrich, Devon K; Horne, Elizabeth F; et al., "Neurocognitive Dysfunction With Neuronal Injury in People With HIV on Long-Duration Antiretroviral Therapy" (2023). Staff and Researcher Publications. 38.
https://digitalcommons.library.tmc.edu/clinic_pub/38