Brain Structural Changes following HIV Infection: Meta-Analysis

O’Connor, Erin E.; Zeffiro, Timothy; Zeffiro, Thomas A.

doi:10.3174/ajnr.a5432

Cited by 45 publications

(39 citation statements)

References 55 publications

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“…Other studies have found no difference in either cortical volume or thickness associated with HIV infection ( Cole et al, 2018 ; Sanford et al, 2018a ; Corrêa et al, 2016a ; Seilhean et al, 1993 ). A recent meta-analysis found that total gray matter volume was significantly smaller among HIV infected individuals than among non-infected controls, although the standardized mean difference was small (−0.28; O'Connor et al, 2018 ). Factors that may explain the inconsistency across studies include viral load at the time of the study ( Kallianpur et al, 2012 ; du Plessis et al, 2016 ; Thompson et al, 2005 ), retroviral treatment status ( Corrêa et al, 2016b ; Ellis et al, 2003 ), and age of the sample ( Ances et al, 2010 ; Jernigan et al, 2005 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of HIV Infection, methamphetamine dependence and age on cortical thickness, area and volume

MacDuffie

Brown

McKenna

et al. 2018

NeuroImage: Clinical

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ObjectiveThis study examined the effects of HIV infection, methamphetamine dependence and their interaction on cortical thickness, area and volume, as well as the potential interactive effects on cortical morphometry of HIV and methamphetamine with age.MethodT1-weighted structural images were obtained on a 3.0T General Electric MR750 scanner. Freesurfer v5.3.0 was used to derive cortical thickness, area and volume measures in thirty-four regions based on Desikan-Killiany atlas labels.ResultsFollowing correction for multiple statistical tests, HIV diagnosis was not significantly related to cortical thickness or area in any ROI, although smaller global cortical area and volume were seen in those with lower nadir CD4 count. HIV diagnosis, nevertheless, was associated with smaller mean cortical volumes in rostral middle frontal gyrus and in the inferior and superior parietal lobes. Methamphetamine dependence was significantly associated with thinner cortex especially in posterior cingulate gyrus, but was not associated with cortical area or volume following correction for multiple statistical tests. We found little evidence that methamphetamine dependence moderated differences in cortical area, volume or thickness for any ROI in the HIV seropositive group. Interactions with age revealed that HIV diagnosis attenuated the degree of age-related cortical thinning seen in non-infected individuals; intercepts indicated that young HIV seropositive individuals had thinner cortex than non-infected peers.ConclusionsMethamphetamine dependence does not appear to potentiate a reduction of cortical area, volume or thickness in HIV seropositive individuals. The finding of thinner cortex in young HIV seropositive individuals and the association between CD4 nadir and global cortical area and volume argue for prioritizing early antiretroviral treatment.

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Section: Introductionmentioning

confidence: 99%

Effects of HIV Infection, methamphetamine dependence and age on cortical thickness, area and volume

MacDuffie

Brown

McKenna

et al. 2018

NeuroImage: Clinical

View full text Add to dashboard Cite

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“…A recent such meta-analysis of 19 published studies, spanning almost three decades, found significantly lower total brain volumes and total gray matter volumes in HIV+ individuals compared to seronegative controls; 6 however, no significant serostatus association with basal ganglia volume was found. In addition, effect sizes were found to be lower in more recent studies compared to older ones, 6 which may suggest a diverging profile of HIV-affected neurocircuitry in more recent years.…”

Section: Discussionmentioning

confidence: 94%

“…1,16 Brain deficits may persist despite cART due to factors such as possible cART neurotoxicity, irreversible brain damage associated with advanced disease, reservoirs of ongoing low-grade viral replication and/or persistent immune activation in the CNS, vascular injury, and neurodegenerative processes that can occur with aging, consistent with the hippocampal findings presented here. 3,4,6,17 In the pre-cART era, HIV-associated dementia was characterized as a "subcortical dementia". In line with reported post mortem neuropathological and viral protein distributions, neuroimaging studies of HIV+ individuals often showed smaller basal ganglia volumes.…”

Section: Discussionmentioning

confidence: 99%

“…18,19 More recently, neuroimaging findings have extended beyond volume differences of the putamen, pallidum, nucleus accumbens and caudate. Serostatus related differences have been detected to varying degrees in the thalamus, 20 amygdala, 21 hippocampus, 22 and even total gray matter, 6 indicating that recent brain alterations may be more dispersed; this may also suggest greater heterogeneity in the causes of brain injury. Once a staple of HIV-related brain alterations, basal ganglia volume associations with CD4+ count or dVL were not detected in the full group of HIV+ participants assessed here, but only in the cARTsubset.…”

Section: Discussionmentioning

confidence: 99%

“…Neuroimaging biomarkers have provided important non-invasive means to understand many psychiatric and neurodegenerative diseases, and to monitor efficacy of clinical interventions. 5 Neuroimaging studies of HIV+ individuals tend to show abnormal volumes of subcortical structures in infected individuals, 6 and associations between such structural changes and NCI; 7 however, inconsistencies in the effect sizes and regional distribution of brain abnormalities associated with CD4+ count or VL in HIV+ individuals have limited the generalizability of the conclusions drawn to date. These inconsistent findings are likely driven in part by differences in demographic characteristics such as age and sex, socioeconomic status, lifestyle factors, history of trauma, substance use, and clinical heterogeneity of study participants, including viral suppression, cART timing/adherence, and other comorbidities.…”

Section: Introductionmentioning

confidence: 99%

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Smaller limbic structures are associated with greater immunosuppression in over 1000 HIV-infected adults across five continents: Findings from the ENIGMA-HIV Working Group

Nir

Fouché

Ananworanich

et al. 2019

Preprint

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Research in Context:Evidence before this study HIV type-1 infection can be managed with antiretroviral therapy, however neurocognitive impairment persists even in treated HIV+ individuals. Given the challenges associated with standardized cognitive testing, there is a need to identify quantitative markers of central nervous system impairment. A number of neuroimaging studies have reported brain abnormalities in HIV-infected patients; however, prior studies investigating associations between CD4+ T-cell count or HIV viral load and subcortical brain volume report variable effect sizes and regional distributions of effects, limiting the generalizability of the conclusions drawn to date. We have conducted a literature search for reports in English language journals published until June 2019, using the following search terms: HIV AND subcortical AND neuroimaging AND brain AND viral load AND RNA AND CD4. After removing studies that were not applicable, there were 30 studies investigating CD4+ T-cell count and viral load associations with subcortical brain structure. Added value of the studyThe aim of the current study was to investigate structural brain associations with two biomarkers universally used to monitor immune function and treatment response, namely plasma RNA viral load and CD4+ T-cell counts. Prior analyses have been performed in smaller, heterogeneous cohorts, but by combining data across cohorts, we can identify consistent associations between brain volume and indicators of HIV infection across cohorts. The ENIGMA-HIV Working Group was established to identify common neurobiological signatures of the HIVinfected brain by harmonizing data analysis from HIV neuroimaging studies worldwide. The value of this dataset is that it is well-powered and representative of many HIV+ people living in the cART era. Implications of all the available evidenceOur results provide robust evidence that despite demographic and clinical heterogeneity among HIV-infected individuals, brain abnormalities are consistently linked to HIV viral load and immunosuppression. This supports the importance of achieving viral suppression and immune system restoration in maintaining brain health in people living with HIV. The vulnerability of limbic regions, found in this study, extends beyond the classically implicated regions of the basal ganglia; this suggests that these regions remain an important target of cART era HIV research, especially given their heightened vulnerability to age-associated atrophy and neurodegeneration.

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Association of Immunosuppression and Viral Load With Subcortical Brain Volume in an International Sample of People Living With HIV

et al. 2021

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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 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 WorkingGroup 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 MEASURESVolume 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] mm 3 per 100 cells/mm 3 ; P < .001) and thalamic (mean [SE] β = 32.24 [8.96] mm 3 per 100 cells/mm 3 ; P < .001) volumes and larger ventricles (mean [SE] β = −391.50 [122.58] mm 3 per 100 cells/mm 3 ; 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] mm 3 per 100 cells/mm 3 ; 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).

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Brain Structural Changes following HIV Infection: Meta-Analysis

Cited by 45 publications

References 55 publications

Effects of HIV Infection, methamphetamine dependence and age on cortical thickness, area and volume

Effects of HIV Infection, methamphetamine dependence and age on cortical thickness, area and volume

Smaller limbic structures are associated with greater immunosuppression in over 1000 HIV-infected adults across five continents: Findings from the ENIGMA-HIV Working Group

Association of Immunosuppression and Viral Load With Subcortical Brain Volume in an International Sample of People Living With HIV

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