The effect of childhood trauma, ApoE genotype and HIV-1 viral protein R variants on change in cognitive performance

Womersley, Jacqueline S.; Clauss, Lara B.; Varathan, Olivette; Engelbrecht, Susan; Hemmings, Sian; Seedat, Soraya; Spies, Georgina

doi:10.1186/s13104-019-4869-9

Cited by 3 publications

(2 citation statements)

References 43 publications

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“…While some work has been done examining social determinants of health in relation to cognitive health among PWH (Dastgheyb et al, 2021; K. J. Petersen et al, 2023; Womersley et al, 2019), more work is needed in large and diverse cohorts. Our prior findings suggest sex differences in the cognitive profiles of PWH (Rubin, Sundermann, et al, 2020); however, the small proportion of women in our sample (12%) precluded sex-stratified analyses that would be adequately powered.…”

Section: Discussionmentioning

confidence: 99%

“…As these social determinants of health have been found to relate to cognitive and brain health among PWH (Dastgheyb et al, 2021; K. J. Petersen et al, 2023; Womersley et al, 2019), this limited our ability to characterize the cognitive profiles and understand the factors driving them. While some work has been done examining social determinants of health in relation to cognitive health among PWH (Dastgheyb et al, 2021; K.…”

Section: Discussionmentioning

confidence: 99%

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Identifying and distinguishing cognitive profiles among virally suppressed people with HIV.

Sundermann,

Dastgheyb,

Moore

et al. 2024

Neuropsychology

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Objective: Cognitive deficits are common among people with HIV (PWH), even when virally suppressed. We identified cognitive profiles among virally suppressed PWH and determined how sociodemographic, clinical/ behavioral, and HIV disease characteristics distinguish profile membership. Method: Participants included 704 virally suppressed PWH (M age = 43.9 [SD = 10.2], 88% male, 58.9% non-Hispanic White) from the HIV Neurobehavioral Research Program. Demographically adjusted T scores were derived from a neuropsychological evaluation comprised of 13 tests. We implemented a pipeline involving dimension reduction and clustering to identify profiles of cognitive performance. Random forest models on a 70/30 training/testing set with internal cross-validation were used to identify sociodemographic, clinical/behavioral, and HIV disease correlates of profile membership. Results: Six cognitive profiles were identified: (a) "unimpaired" (19.9%); (b) weakness in verbal learning and memory (15.5%); (c) weakness in executive function and learning (25.8%); (d) weakness in motor, processing speed, and executive function (8.1%); (e) impaired learning and recall with weak-to-impaired motor, processing speed, and executive function (13.1%); (f) global deficits (17.6%). The most discriminative sociodemographic, clinical/behavioral, and HIV disease characteristics varied by profile with self-reported mood symptoms and cognitive/functional difficulties (e.g., language/communication, memory, and overall everyday function complaints) most consistently associated with profile membership. Conclusions: Cognitive profiles and their associated factors among PWH are heterogeneous, but learning/memory deficits were most common and self-reported mood, and cognitive/ functional difficulties were most consistently related to profile membership. This heterogeneity in cognitive profiles and their correlates in PWH suggests that differing mechanisms contribute to cognitive deficits and, thus, underscores the need for personalized risk reduction and therapeutic strategies among PWH. Key PointsQuestion: Are there common profiles of cognitive impairment among virally suppressed PWH and what are their sociodemographic and health-related correlates? Findings: We found that profiles of cognitive impairment were heterogeneous among PWH although learning/memory deficits were most common and self-reported mood and cognitive/functional difficulties most consistently related to profile membership. Importance: Findings suggest that differing mechanisms contribute to cognitive deficits among PWH and, thus, personalized approaches are needed for risk reduction and therapeutic strategies for cognitive impairment. Next Steps: Future research should examine cognitive profiles in relation to biomarkers to inform mechanisms and test the trajectory of the profile groups over time.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identifying and distinguishing cognitive profiles among virally suppressed people with HIV.

Sundermann,

Dastgheyb,

Moore

et al. 2024

Neuropsychology

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A Pilot Investigation of the Association Between Vpr Amino Acid Substitutions and Peripheral Immune Marker Levels in People With Human Immunodeficiency Virus: Implications for Neurocognitive Impairment

Asia,

Van Vuren,

Kruger

et al. 2024

Open Forum Infectious Diseases

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Background Subtype-specific amino acid variations in viral proteins of HIV-1 influence disease progression. Furthermore, Vpr sequence variation correlates with chronic inflammation, a central mechanism in HIV-1 (neuro)pathogenesis. Nevertheless, no clinical study has investigated the link between Vpr sequence variation and peripheral inflammation in people living with HIV. The aim of this pilot study was to ascertain whether specific Vpr amino acid variants were associated with immune markers in people living with HIV. Methods We included a unique cohort of forty-eight treatment-naïve South African people living with HIV to determine the association between blood-derived Vpr sequence variation and peripheral immune marker levels using Sanger sequencing and ELISA analysis, respectively. Results Our findings indicate that among the many neuropathogenic Vpr amino acid variants and immune markers examined, after applying Bonferroni corrections (p = .05/3) and adjusting for sex and locality, suPAR was nearing significance for higher levels in participants with the G41 amino acid variant compared to those with the S41 variant (p = .035), after. Further, amino acid variations at position 41 (between G41 and S41) exhibited a significant association with suPAR (adj R2 = .089, β = .386; 95% CI .125 to 3.251; p = .035). Conclusions These findings suggest that Vpr amino acid sequence variations might contribute to dysregulated inflammation, which could explain the observed association between specific Vpr variants and HIV-1 (neuro)pathogenesis found in prior research. These Vpr variants merit further investigation to fully understand their roles in HIV-1 pathogenesis and neuropathogenesis.

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Viral protein R (Vpr)-induced neuroinflammation and its potential contribution to neuronal dysfunction: a scoping review

Williams

Naudé

2023

BMC Infect Dis

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HIV-associated neurocognitive disorders (HAND) are the result of the activity of HIV-1 within the central nervous system (CNS). While the introduction of antiretroviral therapy (ART) has significantly reduced the occurrence of severe cases of HAND, milder cases still persist. The persistence of HAND in the modern ART era has been linked to a chronic dysregulated inflammatory profile. There is increasing evidence suggesting a potential role of Viral protein R (Vpr) in dysregulating the neuroinflammatory processes in people living with HIV (PLHIV), which may contribute to the development of HAND. Since the role of Vpr in neuroinflammatory mechanisms has not been clearly defined, we conducted a scoping review of fundamental research studies on this topic. The review aimed to assess the size and scope of available research literature on this topic and provide commentary on whether Vpr contributes to neuroinflammation, as highlighted in fundamental studies. Based on the specified selection criteria, 10 studies (6 of which were cell culture-based and 4 that included both animal and cell culture experiments) were eligible for inclusion. The main findings were that (1) Vpr can increase neuroinflammatory markers, with studies consistently reporting higher levels of TNF-α and IL-8, (2) Vpr induces (neuro)inflammation via specific pathways, including the PI3K/AKT, p38-MAPk, JNK-SAPK and Sur1-Trpm4 channels in astrocytes and the p38 and JNK-SAPK in myeloid cells, and (3) Vpr-specific protein amino acid signatures (73R, 77R and 80A) may play an important role in exacerbating neuroinflammation and the neuropathophysiology of HAND. Therefore, Vpr should be investigated for its potential contribution to neuroinflammation in the development of HAND.

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The effect of childhood trauma, ApoE genotype and HIV-1 viral protein R variants on change in cognitive performance

Cited by 3 publications

References 43 publications

Identifying and distinguishing cognitive profiles among virally suppressed people with HIV.

Identifying and distinguishing cognitive profiles among virally suppressed people with HIV.

A Pilot Investigation of the Association Between Vpr Amino Acid Substitutions and Peripheral Immune Marker Levels in People With Human Immunodeficiency Virus: Implications for Neurocognitive Impairment

Viral protein R (Vpr)-induced neuroinflammation and its potential contribution to neuronal dysfunction: a scoping review

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