Brain Structural Changes following HIV Infection: Meta-Analysis.

Published on Jan 1, 2018in American Journal of Neuroradiology3.381
· DOI :10.3174/AJNR.A5432
Erin E. O'Connor9
Estimated H-index: 9
(University of Maryland Medical System),
Timothy Zeffiro3
Estimated H-index: 3
Thomas A. Zeffiro7
Estimated H-index: 7
BACKGROUND: Numerous studies have used structural neuroimaging to measure HIV effects on brain macroarchitecture. While many have reported changes in total brain volume, gray matter volume, white matter volume, CSF volume, and basal ganglia volume following HIV infection, quantitative inconsistencies observed across studies are large. PURPOSE: Our aim was to evaluate the consistency and temporal stability of serostatus effects on a range of structural neuroimaging measures. DATA SOURCES: PubMed, reference lists, and corresponding authors. STUDY SELECTION: The meta-analysis included 19 cross-sectional studies reporting HIV effects on cortical and subcortical volume from 1993 to 2016. DATA ANALYSIS: Random-effects meta-analysis was used to estimate individual study standardized mean differences and study heterogeneity. Meta-regression was used to examine the effects of the study publication year. DATA SYNTHESIS: Meta-analysis revealed standardized mean differences related to the serostatus of −0.65 ( P = .002) for total brain volume, −0.28 for gray matter volume ( P = .008), −0.24 ( P = .076) for white matter volume, and 0.56 ( P = .001) for CSF volume. Basal ganglia volume differences related to serostatus were not significant. Nevertheless, estimates of between-study heterogeneity suggested that much of the observed variance was between studies. Publication year was associated with recent reductions in many neurostructural effects. LIMITATIONS: Many studies pooled participants with varying durations of treatment, disease, and comorbidities. Image-acquisition methods changed with time. CONCLUSIONS: While published studies of HIV effects on brain structure had substantial variations that are likely to result from changes in HIV treatment practice during the study period, quantitative neurostructural measures can reliably detect the effects of HIV infection during treatment, serving as reliable biomarkers.
📖 Papers frequently viewed together
22 Citations
88 Citations
176 Citations
#1Erin E. O'Connor (University of Maryland Medical System)H-Index: 9
#2Assia Jaillard (French Institute of Health and Medical Research)H-Index: 19
Last. Thomas A. ZeffiroH-Index: 7
view all 4 authors...
BACKGROUND: Diffusion tensor imaging has been widely used to measure HIV effects on white matter microarchitecture. While many authors have reported reduced fractional anisotropy and increased mean diffusivity in HIV, quantitative inconsistencies across studies are numerous. PURPOSE: Our aim was to evaluate the consistency across studies of HIV effects on DTI measures and then examine the DTI reliability in a longitudinal seropositive cohort. DATA SOURCES: Published studies and investigators. ST...
22 CitationsSource
#1Lindsay J. Hines (UND: University of North Dakota)H-Index: 3
#2Eric N. Miller (UCLA: University of California, Los Angeles)H-Index: 61
Last. James T. Becker (University of Pittsburgh)H-Index: 109
view all 13 authors...
To characterize the relationship between dispersion-based intra-individual variability (IIVd) in neuropsychological test performance and brain volume among HIV seropositive and seronegative men and to determine the effects of cardiovascular risk and HIV infection on this relationship. Magnetic Resonance Imaging (MRI) was used to acquire high-resolution neuroanatomic data from 147 men age 50 and over, including 80 HIV seropositive (HIV+) and 67 seronegative controls (HIV-) in this cross-sectional...
19 CitationsSource
CONCISE COMMUNICATION Putamen volume and its clinical and neurological correlates in primary HIV infection Patrick W. Wright a,b , Ashmit Pyakurel c , Florin F. Vaida d , Richard W. Price e , Evelyn Lee e , Julia Peterson e , Dietmar Fuchs f , Henrik Zetterberg g,h , Kevin R. Robertson i , Rudolph Walter j , Dieter J. Meyerhoff j,k , Serena S. Spudich l,M and Beau M. Ances a,b,M Objective: Little is known about the extent of cortical and subcortical volumetric alterations that may occur within t...
26 CitationsSource
#1Diogo Goulart Corrêa (UFRJ: Federal University of Rio de Janeiro)H-Index: 8
#2Nicolle Zimmermann (PUCRS: Pontifícia Universidade Católica do Rio Grande do Sul)H-Index: 11
Last. Emerson L. Gasparetto (UFRJ: Federal University of Rio de Janeiro)H-Index: 31
view all 10 authors...
To evaluate whether human immunodeficiency virus (HIV)-positive patients with and without executive functions deficits and healthy control subjects differ on cortical thickness and subcortical brain structures volume in vivo.In total, 34 HIV-positive patients with executive functions deficits were compared with 13 HIV-positive patients without executive functions deficits and 19 gender-, age-, and education-matched control subjects. Executive functions impairments were classified by performance ...
22 CitationsSource
#1Roland W. Esser (UHH: University of Hamburg)H-Index: 7
#2M. Cornelia Stoeckel (UHH: University of Hamburg)H-Index: 5
Last. Andreas von Leupoldt (Katholieke Universiteit Leuven)H-Index: 30
view all 9 authors...
Background Patients with COPD suffer from chronic dyspnea, which is commonly perceived as highly aversive and threatening. Moreover, COPD is often accompanied by disease-specific fears and avoidance of physical activity. However, little is known about structural brain changes in patients with COPD and respective relations with disease duration and disease-specific fears. Methods This study investigated structural brain changes in patients with COPD and their relation with disease duration, fear ...
41 CitationsSource
#1Sophie CohenH-Index: 10
#2Matthan W.A. CaanH-Index: 30
Last. Dasja PajkrtH-Index: 17
view all 8 authors...
Objective: The current study aims to evaluate the neurologic state of perinatally HIV-infected children on combination antiretroviral therapy and to attain a better insight into the pathogenesis of their persistent neurologic and cognitive deficits. Methods: We included perinatally HIV-infected children between 8 and 18 years and healthy controls matched for age, sex, ethnicity, and socioeconomic status. All participants underwent a 3.0 T MRI with 3D-T1-weighted, 3D–fluid-attenuated inversion re...
56 CitationsSource
#1Marloes A. M. Janssen (Radboud University Nijmegen)H-Index: 5
#2Olga MeulenbroekH-Index: 14
Last. Roy P. C. KesselsH-Index: 32
view all 7 authors...
OBJECTIVE: The objective of the current study is to integrate results from extensive neuropsychological assessment, subjective wellbeing reports and structural neuroimaging findings in successfully treated HIV-infected patients in comparison with a HIV-negative control group. DESIGN: A cross-sectional study. METHODS: Neuropsychological functioning and self-reported wellbeing were assessed in a group of 102 virologically suppressed HIV-infected patients on combination antiretroviral therapy (cART...
31 CitationsSource
#1Guido SchwarzerH-Index: 55
This book provides a comprehensive introduction to performing meta-analysis using the statistical software R. It is intended for quantitative researchers and students in the medical and social sciences who wish to learn how to perform meta-analysis with R. As such, the book introduces the key concepts and models used in meta-analysis. It also includes chapters on the following advanced topics: publication bias and small study effects; missing data; multivariate meta-analysis, network meta-analys...
262 Citations
#1Uraina S. Clark (Brown University)H-Index: 17
#2Keenan A. Walker (St. John's University)H-Index: 1
Last. Karen T. Tashima (Brown University)H-Index: 38
view all 7 authors...
Abstract Impaired facial emotion recognition abilities in HIV+ patients are well documented, but little is known about the neural etiology of these difficulties. We examined the relation of facial emotion recognition abilities to regional brain volumes in 44 HIV-positive (HIV+) and 44 HIV-negative control (HC) adults. Volumes of structures implicated in HIV-associated neuropathology and emotion recognition were measured on MRI using an automated segmentation tool. Relative to HC, HIV+ patients d...
26 CitationsSource
#1Adolf Pfefferbaum (Stanford University)H-Index: 124
#2David A. Rogosa (Stanford University)H-Index: 1
Last. Edith V. Sullivan (Stanford University)H-Index: 111
view all 10 authors...
Abstract Advances in treatment have transformed human immunodeficiency virus (HIV) infection from an inexorable march to severe morbidity and premature death to a manageable chronic condition, often marked by good health. Thus, infected individuals are living long enough that there is a potential for interaction with normal senescence effects on various organ systems, including the brain. To examine this interaction, the brains of 51 individuals with HIV infection and 65 uninfected controls were...
88 CitationsSource
Cited By26
#1E. A. Nickoloff-Bybel (Drexel University)
#2L. Festa (UPenn: University of Pennsylvania)
Last. P. J. Gaskill (Drexel University)
view all 0 authors...
The HIV co-receptors, CCR5 and CXCR4, are necessary for HIV entry into target cells, interacting with the HIV envelope protein, gp120, to initiate several signaling cascades thought to be important to the entry process. Co-receptor signaling may also promote the development of neuroHIV by contributing to both persistent neuroinflammation and indirect neurotoxicity. But despite the critical importance of CXCR4 and CCR5 signaling to HIV pathogenesis, there is only one therapeutic (the CCR5 inhibit...
#1Brandon J. Lew (UNMC: University of Nebraska Medical Center)H-Index: 5
#2Mikki D. Schantell (Boys Town)H-Index: 2
Last. Tony W. Wilson (UNMC: University of Nebraska Medical Center)H-Index: 30
view all 9 authors...
A growing literature suggests a relationship between HIV-infection and a molecular profile of age acceleration. However, despite the widely known high prevalence of HIV-related brain atrophy and HIV-associated neurocognitive disorder (HAND), epigenetic age acceleration has not been linked to HIV-related changes in structural MRI. We applied morphological MRI methods to study the brain structure of 110 virally suppressed participants with HIV infection and 122 uninfected controls age 22-72. All p...
2 CitationsSource
#1Anna PratsH-Index: 11
Last. Carles Soriano-MasH-Index: 45
view all 15 authors...
Integrase strand transfer inhibitors (INSTI) are a main component of the current antiretroviral regimens recommended for treatment of HIV infection. However, little is known about the impact of INSTI on neurocognition and neuroimaging. We developed a prospective observational trial to evaluate the effects of INSTI-based antiretroviral therapy on comprehensive brain outcomes (cognitive, functional, and imaging) according to the time since HIV-1 acquisition. We recruited men living with HIV who in...
#1Yair Mina (TAU: Tel Aviv University)H-Index: 3
#2Tianxia Wu (NIH: National Institutes of Health)H-Index: 33
Last. Bryan Smith (NIH: National Institutes of Health)H-Index: 14
view all 16 authors...
OBJECTIVE To test the hypothesis that brain white matter hyperintensities (WMH) are more common in people living with HIV (PLWH), even in the setting of well-controlled infection, and to identify clinical parameters that correlate with these abnormalities. METHODS Research brain MRI scans, acquired within longitudinal studies evaluating neurocognitive outcomes, were reviewed to determine WMH load using the Fazekas visual rating scale in PLWH with well-controlled infection (antiretroviral therapy...
2 CitationsSource
#1Talia M. Nir (SC: University of Southern California)H-Index: 21
#2Elizabeth Haddad (SC: University of Southern California)H-Index: 7
Last. Neda Jahanshad (SC: University of Southern California)H-Index: 57
view all 4 authors...
In the "cART era" of more widely available and accessible treatment, aging and HIV-related comorbidities, including symptoms of brain dysfunction, remain common among HIV-infected individuals on suppressive treatment. A better understanding of the neurobiological consequences of HIV infection is essential for developing thorough treatment guidelines and for optimizing long-term neuropsychological outcomes and overall brain health. In this chapter, we first summarize magnetic resonance imaging (M...
#1Kalen J Petersen (WashU: Washington University in St. Louis)
#2Nicholas V. Metcalf (WashU: Washington University in St. Louis)H-Index: 11
Last. Beau M. Ances (WashU: Washington University in St. Louis)H-Index: 60
view all 7 authors...
BACKGROUND Persons with HIV (PWH) are characterized by altered brain structure and function. As they attain normal lifespans, it has become crucial to understand potential interactions between HIV and aging. However, it remains unclear how brain aging varies with viral load (VL). METHODS In this study, we compare MRI biomarkers amongst PWH with undetectable VL (UVL; ≤50 genomic copies/ml; n=230), PWH with detectable VL (DVL; >50 copies/ml; n=93), and HIV uninfected (HIV-) controls (n=206). To qu...
#1Mark K. Britton (UF: University of Florida)H-Index: 1
#2Eric C. Porges (UF: University of Florida)H-Index: 19
Last. Ronald A. Cohen (UF: University of Florida)H-Index: 86
view all 4 authors...
Alcohol use disorder (AUD) among people living with HIV (PLWH) is a significant public health concern. Despite the advent of effective antiretroviral therapy, up to 50% of PLWH still experience worsened neurocognition, which comorbid AUD exacerbates. We report converging lines of neuroimaging and neuropsychological evidence linking comorbid HIV/AUD to dysfunction in brain regions linked to executive function, learning and memory, processing speed, and motor control, and consequently to impairmen...
2 CitationsSource
#1Amir H. MeghdadiH-Index: 10
#2Chris BerkaH-Index: 21
Last. Thomas D. Marcotte (UCSD: University of California, San Diego)H-Index: 55
view all 10 authors...
Abstract Objectives The objective of this study was to assess the usability of event-related-potentials (ERPs) during sustained, focused, and divided attention tasks as biomarkers for cognitive decline in HIV patients. Methods EEG was acquired using a mobile/wireless 9-channel system in 39 persons with HIV, with well-controlled immune function and 63 healthy control participants (HCs) during three ERP tasks: sustained attention, focused attention, and divided attention. Results The HIV-group evi...
#1Talia M. Nir (SC: University of Southern California)H-Index: 21
#2Jean-Paul Fouche (UCT: University of Cape Town)H-Index: 19
Last. Neda Jahanshad (SC: University of Southern California)H-Index: 57
view all 39 authors...
Background: Human immunodeficiency virus type-1 (HIV) infection can be controlled with combination antiretroviral therapy (cART), but neurocognitive impairment remains common even in treated and chronic HIV-infected (HIV+) cohorts. Identifying the neuroanatomical pathways associated with infection has the potential to delineate novel neuropathological processes underlying persisting deficits, yet individual neuroimaging studies have yielded inconsistent findings. The ENIGMA-HIV Working Group was...
1 CitationsSource
#1Talia M. Nir (SC: University of Southern California)H-Index: 21
#2Jean-Paul Fouche (UCT: University of Cape Town)H-Index: 19
Last. Lucette A. Cysique (UNSW: University of New South Wales)H-Index: 33
view all 41 authors...
Importance 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...
2 CitationsSource