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Structural brain outcomes in perinatally infected HIV toddlers with early versus late treatments

Poster No:

344 

Submission Type:

Abstract Submission 

Authors:

Arp-Arpa Kasemsantitham1, Watsamon Jantarabenjakul2,3, Montida Veeravigom2, Weerasak Chonchaiya2, Netsiri Dumrongpisutikul4, Pipat Saeyap5, Pannika Vorapaluk5, Thanyawee Puthanakit2,3, Jintanat Anantaworanich6, Kathleen Malee7, Neda Jahanshad8, Paul Thompson8, Chitsanu Pancharoen2, Chaipat Chunharas9,10

Institutions:

1Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 2Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 3Center of Excellence in Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 4Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok,Thailand, 5Department of Anesthesiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 6SEARCH, The Thai Red Cross AIDS Research Center (TRCARC), Bangkok, Thailand, 7Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University, Illinois, United States, 8Imaging Genetics Center, Keck School of Medicine of University of Southern California, California, United States, 9Cognitive Clinical and Computational Neuroscience Lab, Chulalongkorn University, Bangkok, Thailand, 10Chula Neuroscience Center, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand

First Author:

Arp-Arpa Kasemsantitham  
Faculty of Medicine, Chulalongkorn University
Bangkok, Thailand

Co-Author(s):

Watsamon Jantarabenjakul, MD, PhD  
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University|Center of Excellence in Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University
Bangkok, Thailand|Bangkok, Thailand
Montida Veeravigom, MD  
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University
Bangkok, Thailand
Weerasak Chonchaiya  
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University
Bangkok, Thailand
Netsiri Dumrongpisutikul, MD  
Department of Radiology, Faculty of Medicine, Chulalongkorn University
Bangkok,Thailand
Pipat Saeyap, MD  
Department of Anesthesiology, Faculty of Medicine, Chulalongkorn University
Bangkok, Thailand
Pannika Vorapaluk, MD  
Department of Anesthesiology, Faculty of Medicine, Chulalongkorn University
Bangkok, Thailand
Thanyawee Puthanakit, MD  
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University|Center of Excellence in Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University
Bangkok, Thailand|Bangkok, Thailand
Jintanat Anantaworanich  
SEARCH, The Thai Red Cross AIDS Research Center (TRCARC)
Bangkok, Thailand
Kathleen Malee, PhD  
Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University
Illinois, United States
Neda Jahanshad, PhD  
Imaging Genetics Center, Keck School of Medicine of University of Southern California
California, United States
Paul Thompson, PhD  
Imaging Genetics Center, Keck School of Medicine of University of Southern California
California, United States
Chitsanu Pancharoen, MD  
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University
Bangkok, Thailand
Chaipat Chunharas, MD, PhD  
Cognitive Clinical and Computational Neuroscience Lab, Chulalongkorn University|Chula Neuroscience Center, King Chulalongkorn Memorial Hospital, Thai Red Cross Society
Bangkok, Thailand|Bangkok, Thailand

Introduction:

Despite antiretroviral treatments (ARTs), perinatally HIV-infected children still suffer from delayed development and neurocognitive regression. Timing of treatment administration has been shown to impact neurobehavioral outcomes (Jantarabenjakul et., al., 2020); yet, rarely are they investigated on the macro and micro-structural anatomical levels (Laughton et al., 2013). In adults, HIV is known for its white matter abnormalities with sensible damage to the corpus callosum, but results are varied in the pediatric population and remain unclear in toddlers younger than age 5 (Hoare et al., 2014; Sarma et al., 2014; Andronikou et al., 2015; Hoare et al., 2018). This study aimed to investigate whether there are volumetric alterations in neuroimaging outcomes in children receiving early treatments compared to deferred ones. We hypothesize that there will be significant differences in corpus callosal volumes between the two groups. Moreover, we also hypothesize that these differences correlate with changes in neurobehavioral performances, signifying that brain connectivity and functions are overtly affected by the timing of ARTs.

Methods:

Twenty children ages 2 to 5, gender- and age-matched, were initially allocated to either early ART treatments (ART initiated within 3 months of age) (ART-E; n=10) or late ART treatments (ART initiated within 3-12 months of age) (ART-L; n=10). All participants underwent MRI brain imaging on a 3T scanner and neurodevelopmental assessments at two-time points within one year apart. Overall and segmented volumes of the corpus callosum were preprocessed through Freesurfer, examined for quality, and subsequently analyzed. Domains of cognition and neurodevelopment, including motor and language, were evaluated using the Mullen Scales of Early Learning (MSEL) with global development impairment defined as Early Learning Composite (ELC).

Results:

Initial analysis of the corpus callosum through 3-way ANOVA revealed a significant increase in structural volume across sessions (F(1,18)= 13.955, p<0.001); moreover, the ART-L group had marginally smaller corpus callosal volumes compared to those of the ART-E group (F(1,18)= 4.210, p=0.055; Fig. 1). When segmented into five corpus callosal regions, intergroup differences are significantly seen in the mid-anterior region known as the posterior genu (F(1,18) = 2.457, p=0.024; Fig. 2). In regards to neurodevelopment, 2-way ANOVA revealed that the ART-L group had significantly lower ELC scores compared to ART-E (p=0.016), with differences most pronounced in areas of fine motor (p= 0.02) and expressive language (p = 0.002). Mild correlations were found between the corpus callosum volume and neurodevelopmental scores, especially in the fine motor domain (p=0.02).
Supporting Image: Figure1.jpeg
Supporting Image: Figure2.jpeg
 

Conclusions:

The corpus callosum volume in the ART-L group was slightly smaller than the ART-E group, particularly in the posterior genu which correlated with neurodevelopmental score. Differences in structural brain changes and neurodevelopmental outcomes can be seen with possible neuroprotective effects from early treatments for perinatally infected HIV children, revealing the likelihood for compensatory neuroplasticity in the future. We aim to explore these alterations into adulthood, as well as observe changes in other regions of the brain between the two groups.

Disorders of the Nervous System:

Neurodevelopmental/ Early Life (eg. ADHD, autism) 1

Lifespan Development:

Early life, Adolescence, Aging

Modeling and Analysis Methods:

Multivariate Approaches

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

White Matter Anatomy, Fiber Pathways and Connectivity 2

Novel Imaging Acquisition Methods:

Anatomical MRI

Keywords:

Development
Multivariate
PEDIATRIC
STRUCTURAL MRI
White Matter
Other - Perinatal HIV transmission

1|2Indicates the priority used for review

Provide references using author date format

Andronikou, S., Ackermann, C., Laughton, B., Cotton, M., Tomazos, N., Spottiswoode, B., Mauff, K., & Pettifor, J.M. (2015), ‘Corpus callosum thickness on mid-sagittal MRI as a marker of brain volume: a pilot study in children with HIV-related brain disease and controls.’ Pediatric Radiology, vol. 45, no. 7, pp. 1016-25.

Hoare, J., Ransford, G.L., Phillips, N., Amos, T., Donald, K., & Stein DJ. (2014), ‘Systematic review of neuroimaging studies in vertically transmitted HIV positive children and adolescents.’ Metabolic Brain Disease, vol. 29, pp. 221–229.

Hoare, J., Fouche, J.P., Phillips, N., Joska, J.A., Myer, L., Zar, H.J., & Stein, D.J. (2018), ‘Structural brain changes in perinatally HIV infected young adolescents in South Africa.’ AIDS, vol. 32, no. 18, pp. 2707-2718.

Jantarabenjakul, W., Chonchaiya, W., Puthanakit, T., Anugulruengkitt, S., Theerawit, T., Payapanon, J., Sophonphan, J., Veeravigrom, M., Jahanshad, N., Thompson, P.M., Ananworanich, J., Malee, K., & Pancharoen, C. (2020), ‘DOET study. Behavioral problems in perinatally HIV-infected young children with early antiretroviral therapy and HIV-exposed uninfected young children: prevalence and associated factors.’ AIDS Care, vol. 32, no. 4, pp. 429-437.

Laughton, B., Cornell, M., Boivin, M., & Van Rie, A. (2013), ‘Neurodevelopment in perinatally HIV-infected children: a concern for adolescence.’ Journal of International AIDS Society, vol. 16, no.1, pp. 1-11.

Sarma, M.K., Naharajan, R., Keller, M.A., Kumar, R., Nielsen-Saines, L., Michalik, D.E., Deville, J., Church, J.A., & Thomas, A.T. (2014), ‘Regional brain gray and white matter changes in perinatally HIV-infected adolescents.’ Neuroimage: Clinical, vol. 4, pp. 29-34.