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(142) Synergistic Effect of Interpersonal Trauma and HIV Infection on Cortical Thickness and Daily Functioning Despite Viral Suppression


Authors:

Suad Kapetanovic, MD – Assistant Professor of Clinical Psychiatry, University of Southern California

Gina Norato, ScM – Statistician, National Institutes of Health/National Institute of Neurological Disorders and Stroke

Govind Nair, PhD – Investigator, NINDS

Lillian Ham, BA – Research assistant, National Institutes of Health

Joseph Snow, PhD, ABPP-Cn – Staff Scientist, NIMH

Elizabeth Horne, BS – Postbaccalaureate IRTA, NINDS

Brian Agan, MD – Deputy Science Director, USU Infectious Disease Clinical Research Program, HJF

Anuradha Ganesan – Physician, USUHS

Ryan Maves, MD, FCCP, FIDSA – Program Director, Infectious Diseases Fellowship, Naval Medical Center San Diego

Bryan Smith, MD – Staff Clinician, National Institutes of Health


Co-Authors:

Presenting Author: Suad Kapetanovic, MD, University of Southern California
Co-Author: Gina Norato, ScM, National Institutes of Health/National Institute of Neurological Disorders and Stroke
Co-Author: Govind Nair, PhD, NINDS
Co-Author: Lillian Ham, BA, National Institutes of Health
Co-Author: Joseph Snow, PhD, ABPP-Cn, NIMH
Co-Author: Elizabeth Horne, BS, NINDS
Co-Author: Brian Agan, MD, USU Infectious Disease Clinical Research Program, HJF
Co-Author: Anuradha Ganesan, USUHS
Co-Author: Ryan Maves, MD, FCCP, FIDSA, Naval Medical Center San Diego
Co-Author: Bryan Smith, MD, National Institutes of Health

Abstract:

Background/Significance: Interpersonal trauma (IPT) is highly prevalent among HIV-infected (HIV+) individuals but its effect on neuro-cognition is poorly understood. This cross-sectional analysis evaluated the effects of IPT on cognitive task performance, daily functioning, cerebral cortical thickness, and selected basal ganglia (BG) regions in a US-based cohort of aviremic HIV+ adults, with (HIV+IPT+) and without IPT exposure (HIV+IPT-), and socio-demographically matched HIV-negative controls with (HIV-IPT+) and without IPT exposure (HIV-IPT-). We hypothesized there would be a combined effect of HIV and trauma exposure on the outcomes of interest.


Methods:
 Enrollees completed brain MRI studies, a semi-structured psychiatric interview, a neurocognitive battery, and three measures of daily functioning. Demographic and clinical characteristics of the four groups were described, and pairwise between-group comparisons performed using chi-square tests, ANOVA, or t-tests. Linear or Poisson regressions evaluated relationships between group status and the outcomes of interest, in 6 pairwise comparisons, using Bonferroni correction for statistical significance.


Results:
 Among 187 participants (mean age 50.0 years, 63% male), 102 were HIV+IPT+, 35 HIV+IPT-, 26 HIV-IPT, and 24 IPT+HIV-. Compared to the remaining three groups, the HIV+IPT+ group had more Activities of Daily Living (ADL) declines, higher number of impaired Patient’s Assessment of Own Functioning Inventory (PAOFI) scores, and lower cortical thickness in multiple cerebral regions.  Attention/working memory test performances were significantly better in HIV-IPT- compared to HIV+IPT+ and HIV+IPT-. BG MRI volumes were not significantly different in any between-group comparisons.


Discussion:
These results suggest that HIV+ individuals who are survivors of IPT are at risk for neuroHIV complications despite viral suppression, as observed on measures of cortical thickness, cognition, and daily functioning. Reduced regional cortical thickness (i.e., orbitofrontal, cingulate, primary motor and sensory cortex, temporal and frontal lobes) has been reported in a cohort of aviremic HIV+ individuals, as compared to HIV-negative controls, but the study did not account for effect of IPT. Possible mechanisms may include alterations in neuro-immune-endocrine pathways that have been associated with both HIV and trauma, such as alterations in neuro-immune-endocrine pathways that can lead to glial dysfunction and synaptic disintegration and resulting cortical thinning. 

Conclusion/Implications: We observed synergistic effect of IPT exposure and HIV infection on daily functioning, cognition and cortical thickness in aviremic HIV+ individuals. Longitudinal studies are indicated to determine the causality and direction of this effect. Mechanistic studies are needed to further elucidate pathways which may lead to neuroprotective interventions. Future neuroHIV studies must account for the effect of IPT exposure. Studies evaluating relationship between IPT exposure and poor HIV health behaviors and clinical outcomes should consider cortical thinning, impaired daily functioning and lowered attention/working memory performance as key variables of interest

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