Patterns and Predictors of Cognitive Function Among Virally Suppressed Women With HIV

• Type of Material: Article
• Authors: Raha M Dastgheyb, Johns Hopkins University; Alison S Buchholz, Johns Hopkins University; Kathryn C Fitzgerald, Johns Hopkins University; Yanxun Xu, Johns Hopkins University; Dionna W Williams, Johns Hopkins University; Gayle Springer, Johns Hopkins Bloomberg School of Public Health; Kathryn Anastos, Albert Einstein College of Medicine; Deborah R Gustafson, SUNY Downstate Health Sciences University; Amanda B Spence, Georgetown University; Adaora A Adimora, University of North Carolina; Drenna Waldrop, Emory University; David E Vance, University of Alabama Birmingham; Joel Milam, University of Southern California; Hector Bolivar, University of Miami; Kathleen M Weber, Hektoen Institute of Medicine, Chicago; Norman J Haughey, Johns Hopkins University; Pauline M Maki, University of Illinois at Chicago; Leah H Rubin, Johns Hopkins University
• Language: English
• Date: 2021-02-11
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2021 Dastgheyb, Buchholz, Fitzgerald, Xu, Williams, Springer, Anastos, Gustafson, Spence, Adimora, Waldrop, Vance, Milam, Bolivar, Weber, Haughey, Maki and Rubin.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fneur.2021.604984
• Title of Journal or Parent Work: FRONTIERS IN NEUROLOGY
• Volume: 12
• Start Page: 604984
• End Page: 604984
• Grant/Funding Information: The MWCCS was funded primarily by the National Heart, Lung, and Blood Institute (NHLBI), with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Human Genome Research Institute (NHGRI), National Institute on Aging (NIA), National Institute of Dental & Craniofacial Research (NIDCR), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Mental Health (NIMH), National Institute on Drug Abuse (NIDA), National Institute of Nursing Research (NINR), National Cancer Institute (NCI), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). MWCCS data collection was also supported by UL1-TR000004 (UCSF CTSA), P30-AI-050409 (Atlanta CFAR), P30-AI-050410 (UNC CFAR), and P30-AI-027767.; This work was supported by the Johns Hopkins University NIMH Center for novel therapeutics for HIV-associated cognitive disorders (P30MH075773) 2018 pilot award to LR and Johns Hopkins University Center for AIDS Research (CFAR) Scholar Award (P30AI094189 and R03MH123290-02). Data in this manuscript were collected by the Women's Interagency HIV Study, now the MACS/WIHS Combined Cohort Study (MWCCS). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). MWCCS (Principal Investigators): Atlanta CRS (Ighovwerha Ofotokun, Anandi Sheth, and Gina Wingood), U01-HL146241; Baltimore CRS (Todd Brown and Joseph Margolick), U01-HL146201; Bronx CRS (KA and Anjali Sharma), U01-HL146204; Brooklyn CRS (DG and Tracey Wilson), U01-HL146202; Data Analysis and Coordination Center (Gypsyamber D'Souza, Stephen Gange, and Elizabeth Golub), U01-HL146193; Chicago-Cook County CRS (Mardge Cohen and Audrey French), U01-HL146245; Chicago-Northwestern CRS (Steven Wolinsky), U01-HL146240; Connie Wofsy Women's HIV Study, Northern California CRS (Bradley Aouizerat and Phyllis Tien), U01-HL146242; Los Angeles CRS (Roger Detels), U01-HL146333; Metropolitan Washington CRS (Seble Kassaye and Daniel Merenstein), U01-HL146205; Miami CRS (Maria Alcaide, Margaret Fischl, and Deborah Jones), U01-HL146203; Pittsburgh CRS (Jeremy Martinson and Charles Rinaldo), U01-HL146208; UAB-MS CRS (Mirjam-Colette Kempf and Deborah Konkle-Parker), U01-HL146192; UNC CRS (AA), U01-HL146194.
• Keywords: HIV; Clinical Neurology; Neurosciences; women; machine learning; heterogeneity; random forest; cognition; Life Sciences & Biomedicine; Neurosciences & Neurology; Science & Technology; phenotypes
• Research Categories: Mathematics; Psychology, Behavioral; Biology, Neuroscience; Health Sciences, Epidemiology

Abstract

Cognitive impairment remains frequent and heterogeneous in presentation and severity among virally suppressed (VS) women with HIV (WWH). We identified cognitive profiles among 929 VS-WWH and 717 HIV-uninfected women from 11 Women's Interagency HIV Study sites at their first neuropsychological (NP) test battery completion comprised of: Hopkins Verbal Learning Test-Revised, Trail Making, Symbol Digit Modalities, Grooved Pegboard, Stroop, Letter/Animal Fluency, and Letter-Number Sequencing. Using 17 NP performance metrics (T-scores), we used Kohonen self-organizing maps to identify patterns of high-dimensional data by mapping participants to similar nodes based on T-scores and clustering those nodes. Among VS-WWH, nine clusters were identified (entropy = 0.990) with four having average T-scores ≥45 for all metrics and thus combined into an “unimpaired” profile (n = 311). Impaired profiles consisted of weaknesses in: (1) sequencing (Profile-1; n = 129), (2) speed (Profile-2; n = 144), (3) learning + recognition (Profile-3; n = 137), (4) learning + memory (Profile-4; n = 86), and (5) learning + processing speed + attention + executive function (Profile-5; n = 122). Sociodemographic, behavioral, and clinical variables differentiated profile membership using Random Forest models. The top 10 variables distinguishing the combined impaired vs. unimpaired profiles were: clinic site, age, education, race, illicit substance use, current and nadir CD4 count, duration of effective antiretrovirals, and protease inhibitor use. Additional variables differentiating each impaired from unimpaired profile included: depression, stress-symptoms, income (Profile-1); depression, employment (Profile 2); depression, integrase inhibitor (INSTI) use (Profile-3); employment, INSTI use, income, atazanavir use, non-ART medications with anticholinergic properties (Profile-4); and marijuana use (Profile-5). Findings highlight consideration of NP profile heterogeneity and potential modifiable factors contributing to impaired profiles.