TY - JOUR
T1 - Functional connectivity alterations between networks and associations with infant immune health within networks in HIV infected children on early treatment
T2 - A study at 7 years
AU - Toich, Jadrana T.F.
AU - Taylor, Paul A.
AU - Holmes, Martha J.
AU - Gohel, Suril
AU - Cotton, Mark F.
AU - Dobbels, Els
AU - Laughton, Barbara
AU - Little, Francesca
AU - Van Der Kouwe, Andre J.W.
AU - Biswal, Bharat
AU - Meintjes, Ernesta M.
N1 - Funding Information:
This work was supported by NIH grants R01HD071664, R21MH096559, and R21MH108346; South African Medical Research Council (SAMRC); South African National Research Foundation (NRF) grants CPR20110614000019421 and CPRR150723129691; and the NRF/DST South African Research Chairs Initiative. Support for the CHER study, which provided the infrastructure for the neurodevelopmental substudy, was provided by the US National Institute of Allergy and Infectious Diseases through the CIPRA network, Grant U19 AI53217; the Departments of Health of the Western Cape and Gauteng, South Africa; and GlaxoSmithKline/Viiv Healthcare. Additional support was provided with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States Department of Health and Human Services, under Contract No. HHSN272200800014C, and by the NIMH and NINDS Intramural Research Programs of the NIH.
Funding Information:
We thank the participants and their parents for being willing to take part in this study, research assistants Lunges Khethelo and Thandiwe Hamana for their expertise in supporting the children during neuroimaging, the investigators on the CHER Plus Neuro study, and the data management teams at FAMCRU and PHRU. This work was supported by NIH grants R01HD071664, R21MH096559, and R21MH108346; South African Medical Research Council (SAMRC); South African National Research Foundation (NRF) grants CPR20110614000019421 and CPRR150723129691; and the NRF/DST South African Research Chairs Initiative. Support for the CHER study, which provided the infrastructure for the neurodevelopmental substudy, was provided by the US National Institute of Allergy and Infectious Diseases through the CIPRA network, Grant U19 AI53217; the Departments of Health of the Western Cape and Gauteng, South Africa; and GlaxoSmithKline/Viiv Healthcare. Additional support was provided with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States Department of Health and Human Services, under Contract No. HHSN272200800014C, and by the NIMH and NINDS Intramural Research Programs of the NIH.
Publisher Copyright:
© 2018 Toich, Taylor, Holmes, Gohel, Cotton, Dobbels, Laughton, Little, van der Kouwe, Biswal and Meintjes.
PY - 2018/1/11
Y1 - 2018/1/11
N2 - Although HIV has been shown to impact brain connectivity in adults and youth, it is not yet known to what extent long-term early antiretroviral therapy (ART) may alter these effects, especially during rapid brain development in early childhood. Using both independent component analysis (ICA) and seed-based correlation analysis (SCA), we examine the effects of HIV infection in conjunction with early ART on resting state functional connectivity (FC) in 7 year old children. HIV infected (HIV+) children were from the Children with HIV Early Antiretroviral Therapy (CHER) trial and all initiated ART before 18 months; uninfected children were recruited froman interlinking vaccine trial. To better understand the effects of current and early immune health on the developing brain, we also investigated among HIV+ children the association of FC at 7 years with CD4 count and CD4%, both in infancy (6–8 weeks) and at scan. Although we found no differences within any ICA-generated resting state networks (RSNs) between HIV+ and uninfected children (27 HIV+, 18 uninfected), whole brain connectivity to seeds located at RSN connectivity peaks revealed several loci of FC differences, predominantly from seeds in midline regions (posterior cingulate cortex, paracentral lobule, cuneus, and anterior cingulate). Reduced long-range connectivity and increased short-range connectivity suggest developmental delay. Within the HIV+ children, clinical measures at age 7 years were not associated with FC values in any of the RSNs; however, poor immune health during infancy was associated with localized FCincreases in the somatosensory, salience and basal ganglia networks. Together these findings suggest that HIV may affect brain development from its earliest stages and persist into childhood, despite early ART.
AB - Although HIV has been shown to impact brain connectivity in adults and youth, it is not yet known to what extent long-term early antiretroviral therapy (ART) may alter these effects, especially during rapid brain development in early childhood. Using both independent component analysis (ICA) and seed-based correlation analysis (SCA), we examine the effects of HIV infection in conjunction with early ART on resting state functional connectivity (FC) in 7 year old children. HIV infected (HIV+) children were from the Children with HIV Early Antiretroviral Therapy (CHER) trial and all initiated ART before 18 months; uninfected children were recruited froman interlinking vaccine trial. To better understand the effects of current and early immune health on the developing brain, we also investigated among HIV+ children the association of FC at 7 years with CD4 count and CD4%, both in infancy (6–8 weeks) and at scan. Although we found no differences within any ICA-generated resting state networks (RSNs) between HIV+ and uninfected children (27 HIV+, 18 uninfected), whole brain connectivity to seeds located at RSN connectivity peaks revealed several loci of FC differences, predominantly from seeds in midline regions (posterior cingulate cortex, paracentral lobule, cuneus, and anterior cingulate). Reduced long-range connectivity and increased short-range connectivity suggest developmental delay. Within the HIV+ children, clinical measures at age 7 years were not associated with FC values in any of the RSNs; however, poor immune health during infancy was associated with localized FCincreases in the somatosensory, salience and basal ganglia networks. Together these findings suggest that HIV may affect brain development from its earliest stages and persist into childhood, despite early ART.
KW - CD4
KW - Children
KW - Functional connectivity
KW - HIV infection
KW - Neurodevelopment
KW - Resting state networks
KW - Seed-based correlation analysis
KW - fMRI
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U2 - 10.3389/fnhum.2017.00635
DO - 10.3389/fnhum.2017.00635
M3 - Article
AN - SCOPUS:85041326925
SN - 1662-5161
VL - 11
JO - Frontiers in Human Neuroscience
JF - Frontiers in Human Neuroscience
M1 - 635
ER -