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Trajectory Analysis of Cognitive Outcomes in Children With Perinatal HIV

Patel, Payal B. MD*; Apornpong, Tanakorn MS; Puthanakit, Thanyawee MD‡,§; Thongpibul, Kulvadee PhD; Kosalaraksa, Pope MD; Hansudewechakul, Rawiwan MD**; Kanjanavanit, Suparat MD††; Ngampiyaskul, Chiawat MD‡‡; Luesomboon, Wicharn MD§§; Wongsawat, Jurai MD¶¶; Sun, Ly Penh MD‖‖; Chettra, Kea MD, MSc‖‖; Saphonn, Vonthanak MD, MSc, PhD***; Mellins, Claude A. PhD†††; Malee, Kathleen PhD‡‡‡; Spudich, Serena MD, MA*; Ananworanich, Jintanat MD, PhD§§§,¶¶¶; Kerr, Stephen J. MIPH, PhD†‖‖,‖; Paul, Robert PhD**** on behalf of the PREDICT/Resilience Study Group

The Pediatric Infectious Disease Journal: October 2019 - Volume 38 - Issue 10 - p 1038–1044
doi: 10.1097/INF.0000000000002427
HIV Reports

Background: Children with perinatal HIV (pHIV) may display distinct long-term cognitive phenotypes. We used group-based trajectory modeling to identify clusters of children with pHIV after similar developmental trajectories and predictors of belonging to select cognitive trajectory groups.

Methods: Participants included children, 4–17 years of age, with pHIV in Thailand and Cambodia. Cognitive measures included translated versions of Intelligence Quotient tests, Color Trails Tests and Beery-Buktenica Developmental Test of Visual-Motor Integration conducted semiannually over 3–6 years. The best fit of trajectory groups was determined using maximum likelihood estimation. Multivariate logistic regression identified baseline factors associated with belonging to the lowest scoring trajectory group.

Results: Group-based trajectory analyses revealed a 3-cluster classification for each cognitive test, labeled as high, medium and low scoring groups. Most trajectory group scores remained stable across age. Verbal IQ declined in all 3 trajectory groups and the high scoring group for Children’s Color Trails Test 1 and 2 showed an increase in scores across age. Children in the lowest scoring trajectory group were more likely to present at an older age and report lower household income.

Conclusions: Group-based trajectory modeling succinctly classifies cohort heterogeneity in cognitive outcomes in pHIV. Most trajectories remained stable across age suggesting that cognitive potential is likely determined at an early age with the exception of a small subgroup of children who displayed developmental gains in select cognitive domains and may represent those with better cognitive reserve. Poverty and longer duration of untreated HIV may predispose children with pHIV to suboptimal cognitive development.

From the *Department of Neurology, Yale University, New Haven, Connecticut

Department of Statistics, HIV-NAT, The Thai Red Cross AIDS Research Center, Bangkok, Thailand

Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

§Center of Excellence in Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

Department of Psychology, Faculty of Humanities, Chiang Mai University, Chiang Mai, Thailand

Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

**Department of Pediatrics, Infectious Diseases, Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand

††Department of Pediatrics, Infectious Diseases, Nakornping Hospital, Chiang Mai, Thailand

‡‡Prapokklao Hospital, Chantaburi, Thailand

§§Department of Pediatrics, Infectious Diseases, Queen Savang Vadhana Memorial Hospital, Chonburi, Thailand

¶¶Department of Pediatrics, Infectious Diseases, Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand

‖‖Department of Infectious Diseases, Department of Infectious Diseases, National Center for HIV/AIDS Dermatology and STDs, Phnom Penh, Cambodia

***Department of Pediatrics, Infectious Diseases, University of Health Sciences, Phnom Pehn, Cambodia

†††Department of Medical Psychology, HIV Center for Clinical and Behavioral Studies, New York State Psychiatric Institute, and Columbia University, New York, New York

‡‡‡Northwestern University Feinberg School of Medicine, Department of Psychiatry and Behavioral Science, Chicago, Illinois

§§§Department of HIV Therapeutics Research, The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland

¶¶¶Department of Global Health, University of Amsterdam, Amsterdam, The Netherlands

‖‖‖Department of Biostatistics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

****Missouri Institute of Mental Health, University of Missouri-St. Louis, St. Louis, Missouri.

Accepted for publication June 8, 2019.

The PREDICT study was supported by a grant from the National Institute of Allergy and Infectious Diseases of the National Institute of Health through the Comprehensive International Program of Research on AIDS Network (U19 AI53741); cofunded by the Eunice Shriver Kennedy National Institute of Child Health and Human Development and the National Institute of Mental Health. The Resilience study was funded by R01MH102151. The antiretroviral drugs were supported by ViiV Health Care/GlaxoSmithKline, Boehringer-Ingelheim, Merck, Abbott and Roche.

J.A. has received honoraria for participating in advisory meetings for ViiV Healthcare, Merck, AbbVie, Gilead and Roche. The other authors have no conflicts of interest to disclose.

The authors Kerr and Paul are colast authors.

The views expressed are those of the authors and should not be construed to represent the positions of the US Army, the Department of Defense or the Department of Health and Human Services.

See Supplemental Digital Content 1 for Study Group members (

Address for correspondence: Payal B. Patel, MD, 300 George St. Suite 8300, Department of Neurology, Yale University, New Haven, CT.

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.