Association of Immunosuppression and Viral Load With Subcortical Brain Volume in an International Sample of People Living With HIV
AuthorNir, Talia M
Ances, Beau M
Brew, Bruce J
Chaganti, Joga R
Ching, Christopher R K
Cysique, Lucette A
Heaps-Woodruff, Jodi M
Hinkin, Charles H
Joska, John A
Kallianpur, Kalpana J
Lam, Hei Y
Levine, Andrew J
Nakamoto, Beau K
Navia, Bradford A
Porges, Eric C
Salminen, Lauren E
Shikuma, Cecilia M
Thames, April D
Woods, Adam J
Thompson, Paul M
Cohen, Ronald A
Stein, Dan J
JournalJAMA Network Open
PublisherAmerican Medical Association
MetadataShow full item record
AbstractImportance: Despite more widely accessible combination antiretroviral therapy (cART), HIV-1 infection remains a global public health challenge. Even in treated patients with chronic HIV infection, neurocognitive impairment often persists, affecting quality of life. Identifying the neuroanatomical pathways associated with infection in vivo may delineate the neuropathologic processes underlying these deficits. However, published neuroimaging findings from relatively small, heterogeneous cohorts are inconsistent, limiting the generalizability of the conclusions drawn to date. Objective: To examine structural brain associations with the most commonly collected clinical assessments of HIV burden (CD4+ T-cell count and viral load), which are generalizable across demographically and clinically diverse HIV-infected individuals worldwide. Design, Setting, and Participants: This cross-sectional study established the HIV Working Group within the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) consortium to pool and harmonize data from existing HIV neuroimaging studies. In total, data from 1295 HIV-positive adults were contributed from 13 studies across Africa, Asia, Australia, Europe, and North America. Regional and whole brain segmentations were extracted from data sets as contributing studies joined the consortium on a rolling basis from November 1, 2014, to December 31, 2019. Main Outcomes and Measures: Volume estimates for 8 subcortical brain regions were extracted from T1-weighted magnetic resonance images to identify associations with blood plasma markers of current immunosuppression (CD4+ T-cell counts) or detectable plasma viral load (dVL) in HIV-positive participants. Post hoc sensitivity analyses stratified data by cART status. Results: After quality assurance, data from 1203 HIV-positive individuals (mean [SD] age, 45.7 [11.5] years; 880 [73.2%] male; 897 [74.6%] taking cART) remained. Lower current CD4+ cell counts were associated with smaller hippocampal (mean [SE] β = 16.66 [4.72] mm3 per 100 cells/mm3; P < .001) and thalamic (mean [SE] β = 32.24 [8.96] mm3 per 100 cells/mm3; P < .001) volumes and larger ventricles (mean [SE] β = -391.50 [122.58] mm3 per 100 cells/mm3; P = .001); in participants not taking cART, however, lower current CD4+ cell counts were associated with smaller putamen volumes (mean [SE] β = 57.34 [18.78] mm3 per 100 cells/mm3; P = .003). A dVL was associated with smaller hippocampal volumes (d = -0.17; P = .005); in participants taking cART, dVL was also associated with smaller amygdala volumes (d = -0.23; P = .004). Conclusions and Relevance: In a large-scale international population of HIV-positive individuals, volumes of structures in the limbic system were consistently associated with current plasma markers. Our findings extend beyond the classically implicated regions of the basal ganglia and may represent a generalizable brain signature of HIV infection in the cART era.
subcortical brain volume
Enhancing Neuro Imaging Genetics through Meta Analysis (ENIGMA). HIV Working Group
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/14504
- Association of Brain Structure Changes and Cognitive Function With Combination Antiretroviral Therapy in HIV-Positive Individuals.
- Authors: Sanford R, Fellows LK, Ances BM, Collins DL
- Issue date: 2018 Jan 1
- Effects of perinatal HIV-infection on the cortical thickness and subcortical gray matter volumes in young adulthood.
- Authors: Ruiz-Saez B, García MM, de Aragon AM, Gil-Correa M, Melero H, Malpica NA, de Ory SJ, Zamora B, Guillen S, Rojo P, Falcon-Neyra L, Alvarez A, Fernandez P, Lorente-Jareño ML, Ramos JT, Sainz T, Velo C, Navarro ML, Gonzalez-Tomé MI, Cohorte Nacional de VIH pediátrica de la RED RIS (CoRISpe), Madrid, Spain.
- Issue date: 2021 Apr 16
- Connectivity of the Cerebello-Thalamo-Cortical Pathway in Survivors of Childhood Leukemia Treated With Chemotherapy Only.
- Authors: Phillips NS, Kesler SR, Scoggins MA, Glass JO, Cheung YT, Liu W, Banerjee P, Ogg RJ, Srivastava D, Pui CH, Robison LL, Reddick WE, Hudson MM, Krull KR
- Issue date: 2020 Nov 2
- Clinical factors related to brain structure in HIV: the CHARTER study.
- Authors: Jernigan TL, Archibald SL, Fennema-Notestine C, Taylor MJ, Theilmann RJ, Julaton MD, Notestine RJ, Wolfson T, Letendre SL, Ellis RJ, Heaton RK, Gamst AC, Franklin DR Jr, Clifford DB, Collier AC, Gelman BB, Marra C, McArthur JC, McCutchan JA, Morgello S, Simpson DM, Grant I, CHARTER Group.
- Issue date: 2011 Jun
- Antihelminthics in helminth-endemic areas: effects on HIV disease progression.
- Authors: Means AR, Burns P, Sinclair D, Walson JL
- Issue date: 2016 Apr 14