Soluble Biomarkers of Cognition and Depression in Adults with HIV Infection in the Combination Therapy Era

Anderson, Albert M.; Ma, Qing; Letendre, Scott; Iudicello, Jennifer E.

doi:10.1007/s11904-021-00581-y

Cited by 7 publications

(3 citation statements)

References 106 publications

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“…PWH with access to combination antiretroviral therapy (ART) are now predicted to enjoy a life expectancy approaching that of the non-HIV-infected population, largely free of the devastating opportunistic infections that characterized life for PWH during the pre-ART era (1). However, PWH on suppressive ART remain at higher risk for numerous non-AIDS conditions when compared with the general population and display elevated systemic markers of immune-mediated inflammation (2)(3)(4)(5)(6)(7). Viral eradication through HIV cure is therefore the ultimate treatment goal for PWH.…”

Section: Introductionmentioning

confidence: 99%

HIV viral transcription and immune perturbations in the CNS of people with HIV despite ART

Farhadian¹,

Lindenbaum²,

Zhao³

et al. 2022

JCI Insight

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People with HIV (PWH) on antiretroviral therapy (ART) experience elevated rates of neurological impairment, despite controlling for demographic factors and comorbidities, suggesting viral or neuroimmune etiologies for these deficits. Here, we apply multimodal and cross-compartmental single-cell analyses of paired cerebrospinal fluid (CSF) and peripheral blood in PWH and uninfected controls. We demonstrate that a subset of central memory CD4 + T cells in the CSF produced HIV-1 RNA, despite apparent systemic viral suppression, and that HIV-1–infected cells were more frequently found in the CSF than in the blood. Using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), we show that the cell surface marker CD204 is a reliable marker for rare microglia-like cells in the CSF, which have been implicated in HIV neuropathogenesis, but which we did not find to contain HIV transcripts. Through a feature selection method for supervised deep learning of single-cell transcriptomes, we find that abnormal CD8 + T cell activation, rather than CD4 + T cell abnormalities, predominated in the CSF of PWH compared with controls. Overall, these findings suggest ongoing CNS viral persistence and compartmentalized CNS neuroimmune effects of HIV infection during ART and demonstrate the power of single-cell studies of CSF to better understand the CNS reservoir during HIV infection.

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Section: Introductionmentioning

confidence: 99%

HIV viral transcription and immune perturbations in the CNS of people with HIV despite ART

Farhadian¹,

Lindenbaum²,

Zhao³

et al. 2022

JCI Insight

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“…A comprehensive, recently published review of soluble biomarkers of cognition in PLWH brought NfL as the only CNS marker detected in the blood associated with cognition in PLWH. In addition to NfL, markers of HIV persistence (HIV DNA), coinfection (Toxoplasma IgG status), inflammation (chemokines, cytokines, c-reactive protein levels), and immune activation were significantly associated with cognitive status in PLWH [45].…”

Section: Discussionmentioning

confidence: 99%

Blood Biomarkers of Neuronal/Axonal and Glial Injury in Human Immunodeficiency Virus-Associated Neurocognitive Disorders

Rocha

Teixeira

Colpo

et al. 2022

Dement Geriatr Cogn Disord

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Introduction: Approximately half of the people living with HIV (PLWH) experience HIV-associated neurocognitive disorders (HANDs). However, the neuropathogenesis of HAND is complex, and identifying reliable biomarkers has been challenging. Methods: This study included 132 participants aged 50 and older from greater San Diego County. The participants were divided into three groups: PLWH with HAND (n = 29), PLWH without HAND (n = 73), and seronegatives without cognitive impairment (n = 30). Peripheral blood was collected at the clinical assessment, and plasma levels of neurofilament light chain (NfL), phosphorylated Tau 181 (pTau181), and glial fibrillary acidic protein (GFAP) were measured by enzyme-linked immunosorbent assay (ELISA). Results: Plasma levels of NfL (but not pTau181 and GFAP) were significantly associated with HAND at a medium effect size (p = 0.039, Cohen’s d = 0.45 for HAND + vs. HAND−). Notably, higher levels of NfL were significantly associated with HAND diagnosis even after adjusting for sex. Discussion: Our data suggest that neuronal degeneration (as evidenced by increased levels of NfL), but not tau pathology or glial degeneration, is related to cognitive status in PLWH. Our results corroborate the view that blood NfL is a promising biomarker of cognitive impairment in PLWH.

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“…Due to the inherent limitations of NP assessments, research has focused on biological indices to accompany and complement NCI investigations in PLWH [13]. Novel neuroimaging modalities and blood and cerebrospinal fluid (CSF) biomarkers have been extensively investigated to this end, but the incorporation of these tools in a clinical context has not yet been achieved [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Multimodal Approach to Neurocognitive Function in People Living with HIV in the cART Era: A Comprehensive Review

Moschopoulos,

Stanitsa,

Protopapas

et al. 2024

Life

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Combination antiretroviral treatment (cART) has revolutionized the management of human immunodeficiency virus (HIV) and has markedly improved the disease burden and life expectancy of people living with HIV. HIV enters the central nervous system (CNS) early in the course of infection, establishes latency, and produces a pro-inflammatory milieu that may affect cognitive functions, even in the cART era. Whereas severe forms of neurocognitive impairment (NCI) such as HIV-associated dementia have declined over the last decades, milder forms have become more prevalent, are commonly multifactorial, and are associated with comorbidity burdens, mental health, cART neurotoxicity, and ageing. Since 2007, the Frascati criteria have been used to characterize and classify HIV-associated neurocognitive disorders (HAND) into three stages, namely asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD). These criteria are based on a comprehensive neuropsychological assessment that presupposes the availability of validated, demographically adjusted, and normative population data. Novel neuroimaging modalities and biomarkers have been proposed in order to complement NCI assessments, elucidate neuropathogenic mechanisms, and support HIV-associated NCI diagnosis, monitoring, and prognosis. By integrating neuropsychological assessments with biomarkers and neuroimaging into a holistic care approach, clinicians can enhance diagnostic accuracy, prognosis, and patient outcomes. This review interrogates the value of these modes of assessment and proposes a unified approach to NCI diagnosis.

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Soluble Biomarkers of Cognition and Depression in Adults with HIV Infection in the Combination Therapy Era

Cited by 7 publications

References 106 publications

HIV viral transcription and immune perturbations in the CNS of people with HIV despite ART

HIV viral transcription and immune perturbations in the CNS of people with HIV despite ART

Blood Biomarkers of Neuronal/Axonal and Glial Injury in Human Immunodeficiency Virus-Associated Neurocognitive Disorders

Multimodal Approach to Neurocognitive Function in People Living with HIV in the cART Era: A Comprehensive Review

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