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Structural Neuroimaging and Neuropsychologic Signatures of Vertically Acquired HIV

Paul, Robert1; Prasitsuebsai, Wasana2; Jahanashad, Neda3; Puthanakit, Thanyawee2,4; Thompson, Paul3; Aurpibul, Linda5; Hansudewechakul, Rawiwan6; Kosalaraksa, Pope7; Kanjanavanit, Suparat8; Ngampiyaskul, Chaiwat9; Luesomboon, Wicharn10; Lerdlum, Sukalaya11; Pothisri, Mantana11; Visrutaratna, Pannee12; Valcour, Victor13; Nir, Talia, M.3; Saremi, Arvin; Kerr, Stephen2,14,15; Ananworanich, Jintanat2,14,16on behalf of the PREDICT Study Group

The Pediatric Infectious Disease Journal: December 1, 2017 - Volume Publish Ahead of Print - Issue - p
doi: 10.1097/INF.0000000000001852
HIV Reports: PDF Only

BACKGROUND: Children with vertically acquired human immunodeficiency virus (HIV) exhibit persistent cognitive impairments, yet the corresponding neuroimaging signature of vertical infection remains unclear.

METHODS: Fifty healthy control children and 51 vertically infected children were included in the study. The HIV-infected group consisted of survivors who had not received antiretroviral therapy (ART) at birth. The HIV-infected group averaged 11.4 (2.5) years of age, with a median CD4 count of 683 cells/mm3. Most (71%) of the HIV-infected children were on ART for a median of 34 months (range: 33-42) with HIV RNA <40 copies/ml in 89% of the sample. The HIV-uninfected group averaged 10.6 (2.6) years of age. Magnetic resonance imaging was acquired to determine volumes of the caudate, putamen, thalamus, pallidum, hippocampus, nucleus accumbens, total white matter, total gray matter, and cortical gray matter. Correlational analyses examined the degree of shared variance between brain volumes and both cognitive performances and laboratory markers of disease activity (T-cells and plasma viral load).

RESULTS: HIV-infected children exhibited larger volumes of the caudate, nucleus accumbens, total gray matter, and cortical gray matter when compared to the controls. Volumetric differences were predominately evident in children under 12 years of age. HIV-infected children performed worse than controls on most neuropsychological tests, though neither cognitive performances nor laboratory markers corresponded to brain volumes in the HIV-infected children.

CONCLUSIONS: Outcomes of the present study suggest abnormal brain maturation among HIV-infected pediatric survivors. Longitudinal studies of brain integrity and related resilience factors are needed to determine the impact of neuroimaging abnormalities on psychosocial function in pediatric HIV.

1Missouri Institute of Mental Health, University of Missouri-St. Louis, MO, USA

2HIV Netherlands Australia Thailand (HIV-NAT) Research Collaboration, Thai Red Cross AIDS Research Center, Bangkok, Thailand

3Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, CA, USA

4Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

5 Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand

6Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand

7Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

8Nakornping Hospital, Chiang Mai, Thailand

9Prapokklao Hospital, Chantaburi, Thailand

10Queen Savang Vadhana Memorial Hospital, Chongburi, Thailand

11Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

12Department of Radiology, Chiang Mai University, Chiang Mai, Thailand

13Memory and Aging Center, Department of Neurology University of California, San Francisco, CA, USA

14The University of Amsterdam, Amsterdam, The Netherlands

15The Kirby Institute, University of New South Wales, Sydney, Australia

16Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA

Disclaimer: The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army or the Department of Defense

Acknowledgement: The PREDICT study is sponsored by National Institute of Allergy and Infectious Disease (NIAID), Grant number U19 AI053741, Clinical identification number NCT00234091. Antiretoviral drugs for PREDICT are provided by ViiV Healthcare (AZT, 3TC), Boehringer Ingelheim (NVP), Merck (EFV), Abbott (RTV) and Roche (NFV). The neuroimaging and neurodevelopment work are supported by R01MH089722 (PI: Valcour) and R01MH102151 (PI: Ananworanich).

Corresponding Author: Robert Paul. PhD, Missouri Institute of Mental Health, University of Missouri-St. Louis, MO, USA.

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