TY - JOUR
T1 - Lower total and regional grey matter brain volumes in youth with perinatally-acquired HIV infection
T2 - Associations with HIV disease severity, substance use, and cognition
AU - Pediatric HIV/AIDS Cohort Study (PHACS) and the Pediatric Imaging, Neurocognition, and Genetics (PING) Study
AU - Lewis-de los Angeles, C. Paula
AU - Williams, Paige L.
AU - Huo, Yanling
AU - Wang, Shirlene D.
AU - Uban, Kristina A.
AU - Herting, Megan M.
AU - Malee, Kathleen
AU - Yogev, Ram
AU - Csernansky, John G.
AU - Nichols, Sharon
AU - Van Dyke, Russell B.
AU - Sowell, Elizabeth R.
AU - Wang, Lei
N1 - Funding Information:
This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) with co-funding by the National Institute on Drug Abuse (NIDA), the National Institute of Allergy and Infectious Diseases , the Office of AIDS Research , the National Institute of Mental Health , the National Institute of Neurological Disorders and Stroke , the National Institute on Deafness and Other Communication Disorders , the National Heart, Lung, and Blood Institute , the National Institute of Dental and Craniofacial Research , and the National Institute on Alcohol Abuse and Alcoholism through cooperative agreements with the Harvard T. H. Chan School of Public Health (HD052102) and the Tulane University School of Medicine (HD052104). This work was also supported by NIDA (RC2 DA029475) through the Pediatrics Imaging-Genomics Data Resource (PING) study. C.P.L-dlA. was additionally supported by the Northwestern University Training Program in the Neuroscience of Human Cognition (NIH T32 NS047987), the Northwestern University Medical Scientist Training Program (NIH T32 GM008152), and the Dr. John N. Nicholson Fellowship.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Despite improved survival due to combination antiretroviral therapy (cART), youth with perinatally-acquired HIV (PHIV) show cognitive deficits and developmental delay at increased rates. HIV affects the brain during critical periods of development, and the brain may be a persistent reservoir for HIV due to suboptimal blood brain barrier penetration of cART. We conducted structural magnetic resonance imaging (sMRI) and cognitive testing in 40 PHIV youth (mean age = 16.7 years) recruited from the NIH Pediatric HIV/AIDS Cohort Study (PHACS) who are part of the first generation of PHIV youth surviving into adulthood. Historical and current HIV disease severity and substance use measures were also collected. Total and regional cortical grey matter brain volumes were compared to a group of 334 typically-developing, HIV-unexposed and uninfected youth (frequency-matched for age and sex) from the Pediatric Imaging, Neurocognition, and Genetics (PING) study (mean age = 16.1 years). PHIV youth had smaller (2.8–5.1%) total and regional grey matter volumes than HIV-unexposed and uninfected youth, with smallest volumes seen among PHIV youth with higher past peak viral load (VL) and recent unsuppressed VL. In PHIV youth, worse cognitive performance correlated with smaller volumes. This pattern of smaller grey matter volumes suggests that PHIV infection may influence brain development and underlie cognitive dysfunction seen in this population. Among PHIV youth, smaller volumes were also linked to substance use (alcohol use: 9.0–13.4%; marijuana use: 10.1–16.0%). In this study, collection of substance use information was limited to the PHIV cohort; future studies should also collect substance use information in controls to further address interactions between HIV and substance use on brain volume.
AB - Despite improved survival due to combination antiretroviral therapy (cART), youth with perinatally-acquired HIV (PHIV) show cognitive deficits and developmental delay at increased rates. HIV affects the brain during critical periods of development, and the brain may be a persistent reservoir for HIV due to suboptimal blood brain barrier penetration of cART. We conducted structural magnetic resonance imaging (sMRI) and cognitive testing in 40 PHIV youth (mean age = 16.7 years) recruited from the NIH Pediatric HIV/AIDS Cohort Study (PHACS) who are part of the first generation of PHIV youth surviving into adulthood. Historical and current HIV disease severity and substance use measures were also collected. Total and regional cortical grey matter brain volumes were compared to a group of 334 typically-developing, HIV-unexposed and uninfected youth (frequency-matched for age and sex) from the Pediatric Imaging, Neurocognition, and Genetics (PING) study (mean age = 16.1 years). PHIV youth had smaller (2.8–5.1%) total and regional grey matter volumes than HIV-unexposed and uninfected youth, with smallest volumes seen among PHIV youth with higher past peak viral load (VL) and recent unsuppressed VL. In PHIV youth, worse cognitive performance correlated with smaller volumes. This pattern of smaller grey matter volumes suggests that PHIV infection may influence brain development and underlie cognitive dysfunction seen in this population. Among PHIV youth, smaller volumes were also linked to substance use (alcohol use: 9.0–13.4%; marijuana use: 10.1–16.0%). In this study, collection of substance use information was limited to the PHIV cohort; future studies should also collect substance use information in controls to further address interactions between HIV and substance use on brain volume.
KW - Adolescence
KW - Brain
KW - Development
KW - Grey matter
KW - HIV
KW - Magnetic resonance imaging
KW - Neuroimaging
KW - Neuropsychology
KW - Perinatally-acquired
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U2 - 10.1016/j.bbi.2017.01.004
DO - 10.1016/j.bbi.2017.01.004
M3 - Article
C2 - 28089557
AN - SCOPUS:85010617360
SN - 0889-1591
VL - 62
SP - 100
EP - 109
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -