Cognitive Phenotypes of HIV Defined Using a Novel Data-driven Approach

Paul, Robert; Cho, Kyu; Belden, Andrew C.; Martin, Eileen; Bolzenius, Jacob D.; Luckett, Patrick; Cooley, Sarah; Mannarino, Julie; Gilman, Jodi M.; Miano, M.; Ances, Beau M.

doi:10.1007/s11481-021-10045-0

Cited by 8 publications

(9 citation statements)

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“…We also used gradient-boosted multivariate regression (GBM) (40,41) to explore predictors of CD4/CD8 T-cell ratio trajectory cluster classification using the more diverse range of multidimensional information available in the RV254/SEARCH 010 biorepository (e.g., cytokine profiles, cognitive performance, mental health). GBM is a form of ensemble machine learning that yields similar classification accuracy to more computationally intensive methods such as Super Learner (42) while minimizing error due to overfitting (43)(44)(45)(46)(47)(48)(49). We used the Python-based program CatBoost (40,41) to build the GBM models.…”

Section: Discussionmentioning

confidence: 99%

“…Highly correlated features (r > 0.65) were managed by selecting the feature with the highest mutual information criterion value. Consistent with prior work (44)(45)(46)(47), the number of features in the final algorithm was determined by model saturation, defined as the point at which inclusion of additional features resulted in <1 standard deviation gain in classification accuracy relative to the base model. For the current analysis, model saturation was achieved with 10 features.…”

Section: Discussionmentioning

confidence: 99%

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Individual Differences in CD4/CD8 T-Cell Ratio Trajectories and Associated Risk Profiles Modeled From Acute HIV Infection

et al. 2022

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ObjectiveWe examined individual differences in CD4/CD8 T-cell ratio trajectories and associated risk profiles from acute HIV infection (AHI) through 144 weeks of antiretroviral therapy (ART) using a data-driven approach.MethodsA total of 483 AHI participants began ART during Fiebig I–V and completed follow-up evaluations for 144 weeks. CD4+, CD8+, and CD4/CD8 T-cell ratio trajectories were defined followed by analyses to identify associated risk variables.ResultsParticipants had a median viral load (VL) of 5.88 copies/ml and CD4/CD8 T-cell ratio of 0.71 at enrollment. After 144 weeks of ART, the median CD4/CD8 T-cell ratio was 1.3. Longitudinal models revealed five CD4/CD8 T-cell ratio subgroups: group 1 (3%) exhibited a ratio >1.0 at all visits; groups 2 (18%) and 3 (29%) exhibited inversion at enrollment, with normalization 4 and 12 weeks after ART, respectively; and groups 4 (31%) and 5 (18%) experienced CD4/CD8 T-cell ratio inversion due to slow CD4+ T-cell recovery (group 4) or high CD8+ T-cell count (group 5). Persistent inversion corresponded to ART onset after Fiebig II, higher VL, soluble CD27 and TIM-3, and lower eosinophil count. Individuals with slow CD4+ T-cell recovery exhibited higher VL, lower white blood cell count, lower basophil percent, and treatment with standard ART, as well as worse mental health and cognition, compared with individuals with high CD8+ T-cell count.ConclusionsEarly HIV disease dynamics predict unfavorable CD4/CD8 T-cell ratio outcomes after ART. CD4+ and CD8+ T-cell trajectories contribute to inversion risk and correspond to specific viral, immune, and psychological profiles during AHI. Adjunctive strategies to achieve immune normalization merit consideration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Individual Differences in CD4/CD8 T-Cell Ratio Trajectories and Associated Risk Profiles Modeled From Acute HIV Infection

et al. 2022

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“…First, there is the accurate identification and quantitation of medical co-morbidities particularly pre-morbid psychiatric conditions and illness-associated psychological distress 12 . Second, appropriate correction for normative demographic effects are imperative to accurately and specifically determine if cognitive deficits are present and to quantify their severity 13 . Many existing cognitive studies of COVID-19 that used objective testing 14 (Table S1) have not appropriately controlled for demographics, mental health, and comorbid medical conditions.…”

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confidence: 99%

“…Second, appropriate correction for normative demographic effects are imperative to accurately and specifically determine if cognitive deficits are present and to quantify their severity 13 . Many existing cognitive studies of COVID-19 that used objective testing 14 (Table S1) have not appropriately controlled for demographics, mental health, and comorbid medical conditions.…”

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confidence: 99%

Post-acute COVID-19 cognitive impairment and decline uniquely associate with kynurenine pathway activation: a longitudinal observational study

Cysique

Jakabek

Bracken

et al. 2022

Preprint

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Cognitive impairment and function post-acute mild to moderate COVID-19 are poorly understood. We report findings of 128 prospectively studied SARS-CoV-2 positive patients. Cognition and olfaction were assessed at 2-, 4- and 12-months post-diagnosis. Lung function, physical and mental health were assessed at 2-month post diagnosis. Blood cytokines, neuro-biomarkers, and kynurenine pathway (KP) metabolites were measured at 2-, 4-, 8- and 12-months. Mild to moderate cognitive impairment (demographically corrected) was present in 16%, 23%, and 26%, at 2-, 4- and 12-months post diagnosis, respectively. Overall cognitive performance mildly, but significantly (p<.001) declined. Cognitive impairment was more common in those with anosmia (p=.05), but only at 2 months. KP metabolites quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine were significantly (p<.001) associated with cognitive decline. The KP as a unique biomarker offers a potential therapeutic target for COVID-19-related cognitive impairment.

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“…Although HIV-associated neurocognitive disorder was a prominent, debilitating comorbidity in the early days of the HIV epidemic, approximately half of PWH today experience milder forms of neurocognitive impairment ( 4 ). It is also increasingly clear that there are synergistic, bidirectional associations of HIV neuropathogenesis with substance use ( 5 – 7 ), which has been consistently identified as a risk factor for difficulties with HIV disease management and onward HIV transmission ( 8 – 10 ). These enduring social, psychological, and neurobehavioral challenges underscore the continued need for this special issue examining the interaction of HIV with mental health.…”

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confidence: 99%

The Interaction of HIV With Mental Health in the Modern Antiretroviral Therapy Era

Rubin

Paul

2022

Psychosom Med

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People with HIV (PWH) receiving effective antiretroviral therapy (ART) continue to display residual immune dysregulation that amplifies the risk for neuropsychiatric comorbidities. At the same time, PWH commonly experience intersectional stigma and other psychosocial stressors that are linked to neuroendocrine stress responses, potentiate residual immune dysregulation, and alter other biobehavioral processes relevant to health outcomes. This special issue of Psychosomatic Medicine seeks to advance our understanding of the intersection of HIV with mental health in the modern ART era. Several articles cover topics related to the prevalence and treatment of psychiatric comorbidities among PWH such as depression, suicidality, and substance use disorders. Other articles delineate biobehavioral mechanisms relevant to mental health in PWH such as inflammation, immune activation, neuroendocrine signaling, cellular aging, the microbiome-gut-brain axis, and neurobehavioral processes. Collectively, the articles in this special issue highlight the continued importance of biobehavioral and neurobehavioral mental health research in the modern ART era.

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Cognitive Phenotypes of HIV Defined Using a Novel Data-driven Approach

Cited by 8 publications

References 50 publications

Individual Differences in CD4/CD8 T-Cell Ratio Trajectories and Associated Risk Profiles Modeled From Acute HIV Infection

Individual Differences in CD4/CD8 T-Cell Ratio Trajectories and Associated Risk Profiles Modeled From Acute HIV Infection

Post-acute COVID-19 cognitive impairment and decline uniquely associate with kynurenine pathway activation: a longitudinal observational study

The Interaction of HIV With Mental Health in the Modern Antiretroviral Therapy Era

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