Jacqueline Hoare1, Landon Myer2,3, Sarah Heany1, Jean-Paul Fouche1, Nicole Phillips1, Heather J Zar4,5, Dan J Stein1,6. 1. Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa. 2. Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. 3. Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. 4. Department of Pediatrics and Child Health, Red Cross Children's Hospital, UCT, Cape Town, South Africa. 5. SA Medical Research Council Unit on Child and Adolescent Health, South Africa; and. 6. SA Medical Research Council Unit on Risk and Resilience in Mental Disorders, South Africa.
Abstract
OBJECTIVE: To investigate the association between neurocognitive impairment, neuroimaging, and systemic inflammation in perinatally infected adolescents living with HIV (PHIV) on antiretroviral therapy (ART). Systemic inflammation may be one mechanism driving neurocognitive impairment despite ART, but this has not been investigated in adolescence when the brain is undergoing rapid development. SETTING: Cape Town, South Africa. METHODS: Baseline data were drawn from the Cape Town Adolescent Antiretroviral Cohort. PHIV on ART >6 months completed a comprehensive neurocognitive test battery. Diffusion tensor imaging and structural brain magnetic resonance imaging was done to determine whole brain fractional anisotropy, mean diffusion (MD), grey and white matter volumes, and cortical thickness. We examined how neurocognitive and neurostructural measures were associated with a concurrently measured marker of systemic inflammation, high-sensitive C-reactive protein (hs-CRP). RESULTS: One hundred sixty-eight PHIV ages 9-12 years (mean CD4 980 cells/µL; 85.3% viral load <50 copies/mL) and 43 controls were included in the analysis. PHIV had similar hs-CRP (P = 0.17) to controls, after participants with hs-CRP >10 were excluded from the analysis. Forty-eight percent of the PHIV in this analysis have a neurocognitive disorder. Whole brain grey (P = 0.049) and white matter volumes (P = 0.044) were lowest in PHIV with a major neurocognitive disorder. Higher MD, was found in PHIV with a major neurocognitive disorder (P = 0.002). Among PHIV with a neurocognitive disorder, hs-CRP negatively correlated with general intelligence, visual spatial acuity, and executive function (all P = < 0.05). Whole brain MD correlated with higher hs-CRP values (P = < 0.01) in PHIV. CONCLUSIONS: A marker of systemic inflammation was associated with both neurocognitive impairment and MD increases in PHIV.
OBJECTIVE: To investigate the association between neurocognitive impairment, neuroimaging, and systemic inflammation in perinatally infected adolescents living with HIV (PHIV) on antiretroviral therapy (ART). Systemic inflammation may be one mechanism driving neurocognitive impairment despite ART, but this has not been investigated in adolescence when the brain is undergoing rapid development. SETTING: Cape Town, South Africa. METHODS: Baseline data were drawn from the Cape Town Adolescent Antiretroviral Cohort. PHIV on ART >6 months completed a comprehensive neurocognitive test battery. Diffusion tensor imaging and structural brain magnetic resonance imaging was done to determine whole brain fractional anisotropy, mean diffusion (MD), grey and white matter volumes, and cortical thickness. We examined how neurocognitive and neurostructural measures were associated with a concurrently measured marker of systemic inflammation, high-sensitive C-reactive protein (hs-CRP). RESULTS: One hundred sixty-eight PHIV ages 9-12 years (mean CD4 980 cells/µL; 85.3% viral load <50 copies/mL) and 43 controls were included in the analysis. PHIV had similar hs-CRP (P = 0.17) to controls, after participants with hs-CRP >10 were excluded from the analysis. Forty-eight percent of the PHIV in this analysis have a neurocognitive disorder. Whole brain grey (P = 0.049) and white matter volumes (P = 0.044) were lowest in PHIV with a major neurocognitive disorder. Higher MD, was found in PHIV with a major neurocognitive disorder (P = 0.002). Among PHIV with a neurocognitive disorder, hs-CRP negatively correlated with general intelligence, visual spatial acuity, and executive function (all P = < 0.05). Whole brain MD correlated with higher hs-CRP values (P = < 0.01) in PHIV. CONCLUSIONS: A marker of systemic inflammation was associated with both neurocognitive impairment and MD increases in PHIV.
Authors: Leah H Rubin; Lorie Benning; Sheila M Keating; Philip J Norris; Jane Burke-Miller; Antonia Savarese; Krithika N Kumanan; Saria Awadalla; Gayle Springer; Kathyrn Anastos; Mary Young; Joel Milam; Victor G Valcour; Kathleen M Weber; Pauline M Maki Journal: J Neurovirol Date: 2017-10-23 Impact factor: 2.643
Authors: Jacqueline Hoare; Nicole Phillips; John A Joska; Robert Paul; Kirsten A Donald; Dan J Stein; Kevin G F Thomas Journal: Neurology Date: 2016-05-20 Impact factor: 9.910
Authors: Sophie Cohen; Matthan W A Caan; Henk-Jan Mutsaerts; Henriette J Scherpbier; Taco W Kuijpers; Peter Reiss; Charles B L M Majoie; Dasja Pajkrt Journal: Neurology Date: 2015-11-11 Impact factor: 9.910
Authors: Reinhold Schmidt; Helena Schmidt; J David Curb; Kamal Masaki; Lon R White; Lenore J Launer Journal: Ann Neurol Date: 2002-08 Impact factor: 10.422
Authors: Jessica L Montoya; Laura M Campbell; Emily W Paolillo; Ronald J Ellis; Scott L Letendre; Dilip V Jeste; David J Moore Journal: J Acquir Immune Defic Syndr Date: 2019-01-01 Impact factor: 3.731
Authors: Stephen M Smith; Mark Jenkinson; Heidi Johansen-Berg; Daniel Rueckert; Thomas E Nichols; Clare E Mackay; Kate E Watkins; Olga Ciccarelli; M Zaheer Cader; Paul M Matthews; Timothy E J Behrens Journal: Neuroimage Date: 2006-04-19 Impact factor: 6.556
Authors: Gauri Patil; Esau G Mbewe; Pelekelo P Kabundula; Hannah Smith; Sylvia Mwanza-Kabaghe; Alexandra Buda; Heather R Adams; Michael J Potchen; Milimo Mweemba; Brent A Johnson; Giovanni Schifitto; Handy Gelbard; Gretchen L Birbeck; David R Bearden Journal: J Acquir Immune Defic Syndr Date: 2022-10-01 Impact factor: 3.771
Authors: Monray E Williams; Anicia Janse Van Rensburg; Du Toit Loots; Petrus J W Naudé; Shayne Mason Journal: Viruses Date: 2021-12-18 Impact factor: 5.048
Authors: Andrea L Conroy; Robert O Opoka; Paul Bangirana; Ruth Namazzi; Allen E Okullo; Michael K Georgieff; Sarah Cusick; Richard Idro; John M Ssenkusu; Chandy C John Journal: BMC Med Date: 2021-07-28 Impact factor: 8.775
Authors: Stefanie E M van Opstal; Emma J Dogterom; Marlies N Wagener; Femke K Aarsen; Harald S Miedema; Pepijn D D M Roelofs; Linda C van der Knaap; Pieter L A Fraaij; Kim Stol; André B Rietman; Eric C M van Gorp; Annemarie M C van Rossum; Elisabeth M W J Utens Journal: Viruses Date: 2021-09-28 Impact factor: 5.048