Machine Learning Approaches to Understand Cognitive Phenotypes in People With HIV

Mukerji, Shibani S.; Petersen, Kalen J.; Pohl, Kilian M.; Dastgheyb, Raha; Fox, Howard S.; Bilder, Robert M.; Brouillette, Marie‐Josée; Gross, Alden L.; Scott-Sheldon, Lori A. J.; Paul, Robert; Gabuzda, Dana

doi:10.1093/infdis/jiac293

Cited by 17 publications

(9 citation statements)

References 48 publications

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“…Neurocognitive impairment (NCI) remains prevalent among people with HIV despite suppressive ART [22,23]. Mechanisms underlying HIV-associated neurocognitive disorders (HAND), which include asymptomatic neurocognitive impairment (ANI), minor neurocognitive disorder (MND), and HIV-associated dementia (HAD), in ART-treated individuals are multifactorial and include ongoing low-level viral replication in the brain, neuroinflammation, ART neurotoxicity, cerebrovascular disease, and other factors [2,[22][23][24][25]. Although HIV encephalitis (HIVE) is common in untreated HIV+ individuals, it is uncommon in virally suppressed individuals.…”

Section: Introductionmentioning

confidence: 99%

Intact Proviral DNA Analysis of the Brain Viral Reservoir and Relationship to Neuroinflammation in People with HIV on Suppressive Antiretroviral Therapy

Gabuzda

Yin

Misra

et al. 2023

Viruses

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HIV establishes a persistent viral reservoir in the brain despite viral suppression in blood to undetectable levels on antiretroviral therapy (ART). The brain viral reservoir in virally suppressed HIV+ individuals is not well-characterized. In this study, intact, defective, and total HIV proviral genomes were measured in frontal lobe white matter from 28 virally suppressed individuals on ART using the intact proviral DNA assay (IPDA). HIV gag DNA/RNA levels were measured using single-copy assays and expression of 78 genes related to inflammation and white matter integrity was measured using the NanoString platform. Intact proviral DNA was detected in brain tissues of 18 of 28 (64%) individuals on suppressive ART. The median proviral genome copy numbers in brain tissue as measured by the IPDA were: intact, 10 (IQR 1–92); 3′ defective, 509 (225–858); 5′ defective, 519 (273–906); and total proviruses, 1063 (501–2074) copies/106 cells. Intact proviral genomes accounted for less than 10% (median 8.3%) of total proviral genomes in the brain, while 3′ and 5′ defective genomes accounted for 44% and 49%, respectively. There was no significant difference in median copy number of intact, defective, or total proviruses between groups stratified by neurocognitive impairment (NCI) vs. no NCI. In contrast, there was an increasing trend in intact proviruses in brains with vs. without neuroinflammatory pathology (56 vs. 5 copies/106 cells, p = 0.1), but no significant differences in defective or total proviruses. Genes related to inflammation, stress responses, and white matter integrity were differentially expressed in brain tissues with >5 vs. +5 intact proviruses/106 cells. These findings suggest that intact HIV proviral genomes persist in the brain at levels comparable to those reported in blood and lymphoid tissues and increase CNS inflammation/immune activation despite suppressive ART, indicating the importance of targeting the CNS reservoir to achieve HIV cure.

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Section: Introductionmentioning

confidence: 99%

Intact Proviral DNA Analysis of the Brain Viral Reservoir and Relationship to Neuroinflammation in People with HIV on Suppressive Antiretroviral Therapy

Gabuzda

Yin

Misra

et al. 2023

Viruses

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“…First, there are two construct that, while overlapping, represent distinct aspects of cognition. A recent NIMH-sponsored meeting on biotypes of CNS complications in persons living with HIV highlighted the heterogeneity of manifestations of neuro-HIV [ 30 ] and the presence of self-reported cognitive difficulties may represent one phenotype of brain involvement. We did not test the association between biomarkers of gut permeability and a diagnosis of HAND for several reasons.…”

Section: Discussionmentioning

confidence: 99%

Translocation of bacterial LPS is associated with self-reported cognitive abilities in men living with HIV receiving antiretroviral therapy

et al. 2023

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Background Gut damage allows translocation of bacterial lipopolysaccharide (LPS) and fungal β-D-glucan (BDG) into the blood. This microbial translocation contributes to systemic inflammation and risk of non-AIDS comorbidities in people living with HIV, including those receiving antiretroviral therapy (ART). We assessed whether markers of gut damage and microbial translocation were associated with cognition in ART-treated PLWH. Methods Eighty ART-treated men living with HIV from the Positive Brain Health Now Canadian cohort were included. Brief cognitive ability measure (B-CAM) and 20-item patient deficit questionnaire (PDQ) were administered to all participants. Three groups were selected based on their B-CAM levels. We excluded participants who received proton pump inhibitors or antiacids in the past 3 months. Cannabis users were also excluded. Plasma levels of intestinal fatty acid binding protein (I-FABP), regenerating islet-derived protein 3 α (REG3α), and lipopolysaccharides (LPS = were quantified by ELISA, while 1–3-β-D-glucan BDG) levels were assessed using the Fungitell assay. Univariable, multivariable, and splines analyses were performed. Results Plasma levels of I-FABP, REG3α, LPS and BDG were not different between groups of low, intermediate and high B-CAM levels. However, LPS and REG3α levels were higher in participants with PDQ higher than the median. Multivariable analyses showed that LPS association with PDQ, but not B-CAM, was independent of age and level of education. I-FABP, REG3α, and BDG levels were not associated with B-CAM nor PDQ levels in multivariable analyses. Conclusion In this well characterized cohort of ART-treated men living with HIV, bacterial but not fungal translocation was associated with presence of cognitive difficulties. These results need replication in larger samples.

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“…and report them as symptoms, while individuals with HAD present severe cognitive deficits. Despite this categorization attempt, there are studies arguing that the pattern of cognitive impairment is inconsistent among individuals [18,23,24]. In addition, a recent longitudinal study focusing on the progression of NCI found that HAND might not advance invariably [25].…”

Section: Neuropsychological Assessments 21 Understanding Neurocogniti...mentioning

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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Machine Learning Approaches to Understand Cognitive Phenotypes in People With HIV

Cited by 17 publications

References 48 publications

Intact Proviral DNA Analysis of the Brain Viral Reservoir and Relationship to Neuroinflammation in People with HIV on Suppressive Antiretroviral Therapy

Intact Proviral DNA Analysis of the Brain Viral Reservoir and Relationship to Neuroinflammation in People with HIV on Suppressive Antiretroviral Therapy

Translocation of bacterial LPS is associated with self-reported cognitive abilities in men living with HIV receiving antiretroviral therapy

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

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