Neurocognitive decline in <scp>HIV</scp> patients is associated with ongoing T‐cell activation in the cerebrospinal fluid

Grauer, Oliver; Reichelt, D.; Grüneberg, Ute; Lohmann, Hubertus; Schneider‐Hohendorf, Tilman; Schulte‐Mecklenbeck, Andreas; Groß, Catharina C.; Meuth, Sven G.; Wiendl, Heinz; Husstedt, Ingo W.

doi:10.1002/acn3.227

Cited by 42 publications

(28 citation statements)

References 49 publications

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“…38 Both studies suggested that immune activation may actually provide a neuroprotective effect in the pediatric population. This is in stark contrast to the data in the adult population that shows deleterious effects of immune activation on the CNS 39–41 . Both pediatric studies evaluated relatively young children (median age 6–7 years) with perinatal HIV who had only been on cART for a relatively short period of time or who were not on therapy.…”

Section: Discussioncontrasting

confidence: 99%

Neurocognitive Dysfunction in HIV-Infected Youth: Investigating the Relationship with Immune Activation

et al. 2016

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Background HIV-infected individuals are at increased risk of neurocognitive impairment compared to the general population. Studies suggest that, despite combination antiretroviral therapy (cART), HIV infection causes immune activation which results in neural damage; however, few data exist in HIV-infected youth. Methods HIV-infected youth 8–26 years old on cART with virologic suppression were prospectively enrolled along with healthy controls. Neurocognitive performance was assessed by age-appropriate Wechsler Intelligence Scales. Soluble and cellular markers of T-lymphocyte and monocyte activation were measured by ELISA and flow cytometry, respectively. Results 45 HIV-infected subjects and 21 controls were enrolled. Markers of T-cell and monocyte activation were higher in the HIV-infected subjects compared to controls, but proportions of inflammatory and patrolling monocytes were similar. Although there was no significant differences in neurocognitive scores between the HIV-infected and control groups, scores were low-average for 4 of 5 testing domains for the HIV-infected subjects and average for all 5 in the controls, and % of HIV-infected subjects with scores classified as “low average” or below was higher than in the controls. Variables most associated with neurocognitive performance among HIV-infected subjects included activated CD4+ T-cells (% CD4+CD38+HLA-DR), monocyte activation (soluble CD14), HIV duration, age and sex. Conclusions HIV-infected youth on cART with virologic suppression show subtle evidence of neurocognitive impairment compared to healthy controls, and increased immune activation appears to play a role. Additional studies are needed to develop strategic interventions beyond cART to potentially improve neurocognitive performance and/or minimize further impairment in this vulnerable population.

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Section: Discussioncontrasting

confidence: 99%

Neurocognitive Dysfunction in HIV-Infected Youth: Investigating the Relationship with Immune Activation

et al. 2016

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“…[32] While most of the literature has focused on monocyte associations with HAND, it is well recognized that activated lymphocytes can enter and leave the brain, and the contributions of CD8+ T cells producing interferon gamma have recently been associated with HAND as well. [33,34]…”

Section: Biomarkers and Handmentioning

confidence: 99%

HIV-associated neurocognitive disorder

Clifford

2017

Current Opinion in Infectious Diseases

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Purpose of review HIV associated neurocognitive disease (HAND) is the most active topic for neuroAIDS investigations at present. Although impairment is mild in patients successfully treated with modern antiviral regimens, it remains an ongoing problem for HIV patients. It is important to update the emerging research concerning HAND. Recent findings The virus enters the brain during acute infection, with evidence for abnormal functioning that may occur early and often persists. Direct relationships with ongoing viral infection continue to be monitored, but chronic inflammation, often associated with monocytes and macrophages appear to be the most likely driver of cognitive dysfunction. Appreciation for cerebrovascular disease as a significant co-morbidity that is associated with cognitive deficits is increasing. Neuroimaging is actively being developed to address detection and measurement of changes in the brain. Optimal cART therapy has vastly improved neurologic outcomes, but so far has not been demonstrated to reverse the remaining mild impairment. Inflammatory and vascular mechanisms of cerebral dysfunction may need to be addressed to achieve better outcomes. Summary Ongoing research is required to improve neurological outcomes for persons living with HIV. It is likely that interventions beyond antiviral approaches will be required to control or reverse HAND.

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“…Recent work demonstrates that percentage of CD8+ T lymphocytes in CSF, and in particular those that express interferon gamma, positively associate with the presence of HAND even in individuals on virologically successful cART [61]. In an independent study of participants mostly on suppressive cART, increased markers of CSF CD4+ CD8+ T lymphocyte activation and exhaustion correlated with poorer performance on neuropsychological testing and periventricular brain imaging abnormalities suggestive of inflammation [62]. These studies suggest a pathologic role of CNS lymphocyte activation that persists despite cART.…”

Section: Immune Cells and Tissues Involved In Pathogenesismentioning

confidence: 99%

Immune activation in the central nervous system throughout the course of HIV infection

Spudich

2016

Current Opinion in HIV and AIDS

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Purpose of review Robust and dynamic innate and adaptive responses characterize the acute central nervous system (CNS) response to HIV and other viral infections. In a state of chronic infection or viral latency, persistent immune activation associates with pathology in the CNS. Understanding this process is critical, since immune-mediated pathology in non-renewable CNS cells may result in long-term neurologic sequelae for HIV infected individuals. Recent findings In humans, immune activation is reduced by suppressive combination antiretroviral therapy (cART), but persists at abnormally elevated levels on treatment. CNS immune activation is initiated in acute infection and progressively increases until cART is started. Newly identified characteristics of the CNS immune surveillance network include features of homeostasis and function of brain microglial cells, lymphatic drainage from CNS to cervical lymph nodes, and cells in cerebrospinal fluid associated with neurocognitive impairment. Summary More research is required to determine whether early intervention to reduce infection limits the immunopathology established by sustained immune responses that ultimately fail to resolve infection, and to unravel mechanisms of persistent immune activation during treated HIV so that strategies can be developed to therapeutically protect the brain.

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Neurocognitive decline in HIV patients is associated with ongoing T‐cell activation in the cerebrospinal fluid

Cited by 42 publications

References 49 publications

Neurocognitive Dysfunction in HIV-Infected Youth: Investigating the Relationship with Immune Activation

Neurocognitive Dysfunction in HIV-Infected Youth: Investigating the Relationship with Immune Activation

HIV-associated neurocognitive disorder

Immune activation in the central nervous system throughout the course of HIV infection

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