HIV-associated executive dysfunction in the era of modern antiretroviral therapy: A systematic review and meta-analysis

Walker, Keenan A.; Brown, Gregory G.

doi:10.1080/13803395.2017.1349879

Cited by 83 publications

(51 citation statements)

References 122 publications

(115 reference statements)

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“…The signi cant effect of HIV on the TMT-B/A ratio score, along with the signi cant effect of HIV on the Stroop Interference trial, point to a shared underlying cognitive process being impacted in the HIV population, namely cognitive exibility. This observed association between HIV status and cognitive exibility problems adds to the existing literature that has shown impairments in cognitive exibility on other neuropsychological assessments [12,47,48]. Our signi cant nding utilizing the B/A ratio highlights the need to utilize the TMT-B/A ratio score in future studies when investigating the TMT, as it can allow for a more sensitive measure of executive dysfunction.…”

Section: Discussionsupporting

confidence: 56%

“…There has been a lack of comparison between different executive functioning measures in individuals living with HIV who also have cocaine dependence. A recent systematic review and meta-analysis [12] pointed out the considerable differences within the conceptualization and measurement of executive functioning within the HIV population. Overall, there is a consensus that executive functioning impairments exist within both the HIV population and the cocaine dependence population.…”

Section: Introductionmentioning

confidence: 99%

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Specific Aspects of Executive Functioning Impacted in HIV and Cocaine Dependence

Nigro¹,

Wu²,

Lord³

et al. 2020

Preprint

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Background: Our study aimed to understand the effects of HIV and cocaine dependence (CD) on discrete aspects of executive functioning via the Stroop Color-Word Test and the Trail Making Test (TMT). We recruited 101 participants (26 HIV+/CD+; 18 HIV+/CD-; 30 HIV-/CD+; and 27 HIV-/CD-. Methods: We utilized a series of 2 (HIV: yes/no) × 2 (Cocaine: yes/no) ANCOVA’s while controlling for age and premorbid intelligence on the Stroop trials (i.e., color-naming, word reading, interference), and ANOVA’s were used to test for group differences on TMT-A and TMT-B z-scores, the number of errors, and the B/A ratio score. Results: We found a significant main effect of HIV on the Stroop Interference (p = 0.012) and the TMT B/A ratio (p = 0.017), these findings are consistent with difficulties in cognitive flexibility. On the Color-Naming and Interference trials, individuals with CD made significantly more errors than non-users (p = 0.028), demonstrating difficulties with inhibition. Conclusions: Our results show HIV and CD are associated with different underlying cognitive processes which impact overall executive functioning. Understanding the different cognitive factors impacting executive functioning can help formulate tailored treatment recommendations and targeted interventions for people living with HIV and those with cocaine dependence.

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Section: Discussionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Specific Aspects of Executive Functioning Impacted in HIV and Cocaine Dependence

Nigro¹,

Wu²,

Lord³

et al. 2020

Preprint

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“…The frontal/ACC (especially the ACC) receives rich dopaminergic innervation as part of the mesocortical pathway that originates from dopaminergic neurons in the ventral tegmental area (Nolan & Gaskill, ), and studies have suggested that the mesocortical dopamine fibers projection to the prefrontal cortex and ACC is important for executive function, working memory, motivation, and emotion [Nolan & Gaskill, ]. Here we hypothesized that the injury to the dopaminergic system in HIV (Chang et al, ; Kumar et al, ; Nath et al, ) might have contributed to the high prevalence of frontal/ACC atrophy, as well as executive dysfunction (Heaton et al, ) and apathy (Paul et al, ; Walker & Brown, ) in HIV+ adults. Future studies with multimodal neuroimaging techniques along with comprehensive neuropsychology tests are needed to test this hypothesis.…”

Section: Discussionmentioning

confidence: 94%

“…The hypothesis of early ACC dysfunction in HIV‐disease is also supported by the high prevalence of apathy in HIV (Paul et al, ; Walker & Brown, ), even in those with acute infection (Kamat et al, ). Neuropsychology studies (Cummings, ) have revealed a direct link between apathy and lesions to the ACC, suggesting the high prevalence of apathy in HIV might be associated with the highly prevalence of ACC injury.…”

Section: Discussionmentioning

confidence: 97%

Different roles of frontal versus striatal atrophy in HIV‐associated neurocognitive disorders

Israel

Hassanzadeh‐Behbahani

Turkeltaub

et al. 2019

Human Brain Mapping

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Gray matter (GM) atrophy is frequently detected in persons living with HIV, even in the era of combination antiretroviral therapy (cART), but the specificity of regions affected remains elusive. For instance, which regions are consistently affected in HIV? In addition, atrophy at which regions is frequently associated with neurocognitive impairment in HIV? Resolving these questions can potentially help to establish the possible neural profiles of HIV‐associated neurocognitive disorders (HAND) severity, which currently is solely defined by neurobehavioral assessments. Here, we addressed these questions using a novel meta‐analysis technique, the colocalization‐likelihood estimation (CLE) technique, to quantitatively synthesize the findings of GM atrophy in HIV+ adults. Twenty‐one of 386 studies published between 1988 and November 2017 and identified in PubMed were selected, plus four identified in other resources. In the end, 25 studies (1,370 HIV+ adults, 889 HIV− controls) were included in the meta‐analysis. This technique revealed that GM atrophy in HIV+ adults was dominated by two distinct but nonexclusive profiles: frontal (including anterior cingulate cortex, [ACC]) atrophy, which was associated withHIV‐disease and consistently differentiated HIV+ adults from HIV− controls; and caudate/striatum atrophy, which was associated with neurocognitive impairment. The critical role of caudate/striatum atrophy in neurocognitive impairment was further supported by a separate data analysis, which examined the findings of correlation analyses between GM and neurocognitive performance. These results suggest that the frontal lobe and the striatum play critical but differential roles in HAND. A neural model of HAND severity was proposed with several testable predictions.

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“…Spatial learning, spatial memory, and working memory are three of seven cognitive ability criteria evaluated during neuropsychological (NP) diagnosis of mild NCI [ 6 ] and they are frequently affected in patients on HIV-suppressive ART (reviewed in [ 9 , 10 ]). The impairment of associative memory in infected mice shown in FC behavioral tests may be indicative of neuropsychiatric disorders also affecting HIV-positive individuals [ 111 – 114 ]. Although rodents and rodent behavioral tests do not fully reproduce the complexity of human behavior, our results indicate that murine HIV-NCI reflects some cognitive abnormalities seen in HIV-positive patients.…”

Section: Discussionmentioning

confidence: 99%

EcoHIV infection of mice establishes latent viral reservoirs in T cells and active viral reservoirs in macrophages that are sufficient for induction of neurocognitive impairment

et al. 2018

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Suppression of HIV replication by antiretroviral therapy (ART) or host immunity can prevent AIDS but not other HIV-associated conditions including neurocognitive impairment (HIV-NCI). Pathogenesis in HIV-suppressed individuals has been attributed to reservoirs of latent-inducible virus in resting CD4+ T cells. Macrophages are persistently infected with HIV but their role as HIV reservoirs in vivo has not been fully explored. Here we show that infection of conventional mice with chimeric HIV, EcoHIV, reproduces physiological conditions for development of disease in people on ART including immunocompetence, stable suppression of HIV replication, persistence of integrated, replication-competent HIV in T cells and macrophages, and manifestation of learning and memory deficits in behavioral tests, termed here murine HIV-NCI. EcoHIV established latent reservoirs in CD4+ T lymphocytes in chronically-infected mice but could be induced by epigenetic modulators ex vivo and in mice. In contrast, macrophages expressed EcoHIV constitutively in mice for up to 16 months; murine leukemia virus (MLV), the donor of gp80 envelope in EcoHIV, did not infect macrophages. Both EcoHIV and MLV were found in brain tissue of infected mice but only EcoHIV induced NCI. Murine HIV-NCI was prevented by antiretroviral prophylaxis but once established neither persistent EcoHIV infection in mice nor NCI could be reversed by long-acting antiretroviral therapy. EcoHIV-infected, athymic mice were more permissive to virus replication in macrophages than were wild-type mice, suffered cognitive dysfunction, as well as increased numbers of monocytes and macrophages infiltrating the brain. Our results suggest an important role of HIV expressing macrophages in HIV neuropathogenesis in hosts with suppressed HIV replication.

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HIV-associated executive dysfunction in the era of modern antiretroviral therapy: A systematic review and meta-analysis

Abstract: Our results suggest that discrete domains of EF may be differentially affected by HIV infection and moderating demographic and clinical variables. These findings have implications for the development of targeted cognitive remediation strategies.

Cited by 83 publications

References 122 publications

Specific Aspects of Executive Functioning Impacted in HIV and Cocaine Dependence

Specific Aspects of Executive Functioning Impacted in HIV and Cocaine Dependence

Different roles of frontal versus striatal atrophy in HIV‐associated neurocognitive disorders

EcoHIV infection of mice establishes latent viral reservoirs in T cells and active viral reservoirs in macrophages that are sufficient for induction of neurocognitive impairment

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