14 research outputs found
Dietary Intake Is Associated With Neuropsychological Impairment in Women With HIV
Background
Diet is a modifiable risk factor that may influence cognition in people with HIV.
Objectives
We examined the association between dietary intake and cognition in women with HIV (WWH) and HIV-seronegative women.
Methods
An 18-item dietary National Cancer Institute screener was completed by 729 WWH and 346 HIV-seronegative Women\u27s Interagency HIV Study participants. Daily intake frequencies of processed meats, sweet beverages, fish, whole milk, and vegetables were calculated. Participants completed biennial neuropsychological (NP) testing. NP domains included attention/working memory, executive function, processing speed, memory, learning, fluency, and motor function. NP impairment was defined as demographically adjusted T-scores (mean = 50; SD = 10) ≤40 at ≥1 visit after completing the dietary screener. Multivariable logistic regression, stratified by HIV serostatus, examined associations between intake frequency tertile (referent = lowest intake) and NP performance.
Results
Dietary intake frequencies of individual food line items were similar between WWH and HIV-seronegative women, except for sweet beverages, for which HIV-seronegative women reported higher intake frequencies than WWH (P values \u3c 0.05). In WWH, multivariable-adjusted models indicated higher odds of NP impairment with higher intake frequencies of processed meat [P = 0.006; ORupper tertile = 1.91 (95% CI: 1.23–2.95; P = 0.003); ORmiddle tertile = 1.66 (95% CI: 1.14–2.42; P = 0.01)], sweet beverages [P = 0.02; ORupper tertile = 1.75 (95% CI: 1.17–2.64; P = 0.007)], fish [P = 0.01; ORupper tertile = 1.70 (95% CI: 1.10–2.64; P = 0.02)], and whole milk [P = 0.029; ORupper tertile = 1.66 (95% CI: 1.14–2.42; P = 0.008)]. Lower odds of NP impairment [P = 0.005; ORupper tertile = 0.65 (95% CI: 0.45–0.95; P = 0.02); ORmiddle tertile = 0.42 (95% CI: 0.24–0.73; P = 0.002)] were associated with higher vegetable intakes. In HIV-seronegative women, multivariable-adjusted models did not show associations between food line items/diet quality score and NP outcomes.
Conclusions
Intakes of processed meat, sweet beverages, whole milk, fish, and vegetables may be associated with NP functions among WWH. Associations among WWH are not directly comparable to those among HIV-seronegative women, because models were conducted on each group separately given controls for HIV-specific covariates in WWH. Further studies are needed using more rigorous dietary assessment methods and lengthier longitudinal follow-ups
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Cognitive Trajectory Phenotypes in Human Immunodeficiency Virus-Infected Patients.
ObjectiveThe presentation of cognitive impairments in HIV-infected individuals has transformed since the introduction of antiretroviral therapies. Although the overall prevalence of cognitive impairments has not changed considerably, frank dementia is now infrequent, and milder forms of cognitive impairments predominate. Mechanistic insights to the underlying causes of these residual cognitive impairments have been elusive, in part due to the heterogenous etiology of cognitive dysfunction in this population. Here, we sought to categorize longitudinal change in HIV-infected patients based on the performance in specific cognitive domains.DesignThis study consisted of 193 participants from the CHARTER cohort with detailed demographic, clinical, and neuropsychological testing data obtained from 2 study visits interspersed by ∼6 months. Cognitive testing assessed executive function, learning and delayed recall, working memory, verbal fluency, speed of information processing, and motor skills. Change scores were calculated for each domain between the 2 study visits. Dimension reduction and clustering was accomplished by principal component analysis of change scores and k-means clustering to identify cognitive domains that group together and groups of subjects with similar patterns of change.ResultsWe identified 4 distinct cognitive change phenotypes that included declines in: (1) verbal fluency, (2) executive function (3) learning and recall, and (4) motor function, with approximately equal numbers of participants in each phenotype.ConclusionsEach of the 4 cognitive change phenotypes identify deficits that imply perturbations in specific neural networks. Future studies will need to validate if cognitive change phenotypes are associated with alterations in associated neural pathways
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Machine Learning Approaches to Understand Cognitive Phenotypes in People With HIV
Cognitive disorders are prevalent in people with HIV (PWH) despite antiretroviral therapy. Given the heterogeneity of cognitive disorders in PWH in the current era and evidence that these disorders have different etiologies and risk factors, scientific rationale is growing for using data-driven models to identify biologically defined subtypes (biotypes) of these disorders. Here, we discuss the state of science using machine learning to understand cognitive phenotypes in PWH and their associated comorbidities, biological mechanisms, and risk factors. We also discuss methods, example applications, challenges, and what will be required from the field to successfully incorporate machine learning in research on cognitive disorders in PWH. These topics were discussed at the National Institute of Mental Health meeting on "Biotypes of CNS Complications in People Living with HIV" held in October 2021. These ongoing research initiatives seek to explain the heterogeneity of cognitive phenotypes in PWH and their associated biological mechanisms to facilitate clinical management and tailored interventions
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Early Inflammatory Signatures Predict Subsequent Cognition in Long-Term Virally Suppressed Women With HIV.
Immunologic function is an important determinant of cognition. Here we examined the contribution of early immune signatures to cognitive performance among HIV-infected, virally suppressed women (HIV+VS) and in HIV-uninfected (HIV-) women. Specifically, we measured serum inflammatory markers, developed combinatory immune signatures, and evaluated their associations with cognition. Forty-nine HIV+VS women in the Women's Interagency HIV Study (WIHS) who achieved viral suppression shortly after effective antiretroviral therapy (ART) initiation, and 56 matched HIV- women were selected. Forty-two serum inflammatory markers were measured within 2 years of effective ART initiation for HIV+VS women, and at an initial timepoint for HIV- women. The same inflammatory markers were also measured approximately 1, 7, and 12 years later for all women. Of the 105 women with complete immune data, 83 (34 HIV+VS, 49 HIV-) also had cognitive data available 12 years later at ≥1 time points (median = 3.1). We searched for combinatory immune signatures by adapting a dynamic matrix factorization analytic method that builds upon Tucker decomposition followed by Ingenuity® Pathway Analysis to facilitate data interpretation. Seven combinatory immune signatures emerged based on the Frobenius residual. Three signatures were common between HIV+VS and HIV- women, while four signatures were unique. These inflammatory signatures predicted subsequent cognitive performance in both groups using mixed-effects modeling, but more domain-specific associations were significant in HIV+VS than HIV- women. Leukocyte influx into brain was a major contributor to cognitive function in HIV+VS women, while T cell exhaustion, inflammatory response indicative of depressive/psychiatric disorders, microglial activity, and cytokine signaling predicted both global and domain-specific performance for HIV- women. Our findings suggest that immune signatures may be useful diagnostic, prognostic, and immunotherapeutic targets predictive of subsequent cognitive performance. Importantly, they also provide insight into common and distinct inflammatory mechanisms underlying cognition in HIV- and HIV+VS women
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Common antiretroviral combinations are associated with somatic depressive symptoms in women with HIV
Objective: While modern antiretroviral therapy (ART) is highly effective and safe, depressive symptoms have been associated with certain ART drugs. We examined the association between common ART regimens and depressive symptoms in women with HIV (WWH) with a focus on somatic vs. non-somatic symptoms. Design: Analysis of longitudinal data from the Women's Interagency HIV Study. Methods: Participants were classified into three groups based on the frequency of positive depression screening (CES-D ≥16): chronic depression (≥50% of visits since study enrollment), infrequent depression (<50% of visits), and never depressed (no visits). Novel Bayesian machine learning methods building upon a subset-tree kernel approach were developed to estimate the combined effects of ART regimens on depressive symptoms in each group after covariate adjustment. Results: The analysis included 1,538 WWH who participated in 12,924 (mean = 8.4) visits. The mean age was 49.9 years, 72% were Black, and 14% Hispanic. In the chronic depression group, combinations including tenofovir alafenamide and cobicistat-boosted elvitegravir and/or darunavir were associated with greater somatic symptoms of depression, whereas those combinations containing tenofovir disoproxil fumarate and efavirenz or rilpivirine were associated with less somatic depressive symptoms. ART was not associated with somatic symptoms in the infrequent depression or never depressed groups. ART regimens were not associated with non-somatic symptoms in any group. Conclusions: Specific ART combinations are associated with somatic depressive symptoms in WWH with chronic depression. Future studies should consider specific depressive symptoms domains as well as complete drug combinations when assessing the relationship between ART and depression
Associations between Antiretroviral Drugs on Depressive Symptomatology in Homogenous Subgroups of Women with HIV
Antiretroviral therapy (ART) is inconsistently associated with depression. These associations may depend on factors such as biological sex, age, and health status. Identifying such factors may help optimize treatment of HIV and depression. We implemented a novel approach to examine interindividual variability in the association between ART agents and depressive symptoms. 3434 women living with HIV (WLWH) from the Women's Interagency HIV Study (WIHS) were computationally divided into subgroups based on sociodemographic (e.g., age) and longitudinal (from 1995 to 2016) behavioral and clinical profiles (e.g., substance use, HIV RNA, CD4 counts). Five subgroups (n's ranged from 482 to 802) were identified and characterized as those with: controlled HIV/vascular comorbidities; profound HIV legacy effects; younger women [<45 years of age] with hepatitis C; primarily 35-55 year olds; and poorly controlled HIV/substance use. Within each subgroup, we examined associations between ART agents used over the past 6 months and item-level depressive symptoms on the Center for Epidemiologic Studies Depression Scale. Tenofovir (4 of 5 subgroups) followed by efavirenz, emtricitabine, stavudine, lopinavir, etravirine, nelfinavir, ritonavir, and maraviroc were the most common agents associated with depressive symptoms, although the pattern and directionality varied by subgroup. For example, lopinavir was associated with fewer symptoms among the subgroup with a legacy HIV effect but more symptoms among the subgroup with well-controlled HIV/vascular comorbidities. Unexpectedly, dolutegravir and raltegravir were not associated with depressive symptoms among any subgroup. Findings underscore marked interindividual variability in ART agents on depression in WLWH. Sociodemographic, clinical, and behavioral factors are important determinants of the relationship between ART agents and depressive symptoms in WLWH. Graphical Abstract Are antiretroviral agents a risk factor for depressive symptoms in women with HIV? We examined associations between ART-agents and depressive symptoms among similar subgroups of women with HIV from the Women's Interagency HIV Study. The patterns of associations depended on sociodemographic, clinical, and behavioral characteristics of women
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Factors Predicting Detrimental Change in Declarative Memory Among Women With HIV: A Study of Heterogeneity in Cognition
Associations between Antiretrovirals and Cognitive Function in Women with HIV
Cognitive complications persist in antiretroviral therapy(ART)-treated people with HIV. However, the pattern and severity of domain-specific cognitive performance is variable and may be exacerbated by ART-mediated neurotoxicity. 929 women with HIV(WWH) from the Women's Interagency HIV Study who were classified into subgroups based on sociodemographic and longitudinal behavioral and clinical data using semi-parametric latent class trajectory modelling. Five subgroups were comprised of: 1) well-controlled HIV with vascular comorbidities(n = 116); 2) profound HIV legacy effects(CD4 nadir n = 275); 3) primarily <45 year olds with hepatitis C(n = 165); 4) primarily 35-55 year olds(n = 244), and 5) poorly-controlled HIV/substance use(n = 129). Within each subgroup, we fitted a constrained continuation ratio model via penalized maximum likelihood to examine adjusted associations between recent ART agents and cognition. Most drugs were not associated with cognition. However, among the few drugs, non-nucleoside reverse transcriptase inhibitor (NNRTIs) and protease inhibitors(PIs) were most commonly associated with cognition, followed by nucleoside reverse transcriptase inhibitors(NRTIs) and integrase inhibitors(IIs). Directionality of ART-cognition associations varied by subgroup. Better psychomotor speed and fluency were associated with ART for women with well-controlled HIV with vascular comorbidities. This pattern contrasts women with profound HIV legacy effects for whom poorer executive function and fluency were associated with ART. Motor function was associated with ART for younger WWH and primarily 35-55 year olds. Memory was associated with ART only for women with poorly-controlled HIV/substance abuse. Findings demonstrate interindividual variability in ART-cognition associations among WWH and highlight the importance of considering sociodemographic, clinical, and behavioral factors as an underlying contributors to cognition
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Dietary intake is associated with neuropsychological impairment in women with HIV.
BackgroundDiet is a modifiable risk factor that may influence cognition in people with HIV.ObjectivesWe examined the association between dietary intake and cognition in women with HIV (WWH) and HIV-seronegative women.MethodsAn 18-item dietary National Cancer Institute screener was completed by 729 WWH and 346 HIV-seronegative Women's Interagency HIV Study participants. Daily intake frequencies of processed meats, sweet beverages, fish, whole milk, and vegetables were calculated. Participants completed biennial neuropsychological (NP) testing. NP domains included attention/working memory, executive function, processing speed, memory, learning, fluency, and motor function. NP impairment was defined as demographically adjusted T-scores (mean = 50; SD = 10) ≤40 at ≥1 visit after completing the dietary screener. Multivariable logistic regression, stratified by HIV serostatus, examined associations between intake frequency tertile (referent = lowest intake) and NP performance.ResultsDietary intake frequencies of individual food line items were similar between WWH and HIV-seronegative women, except for sweet beverages, for which HIV-seronegative women reported higher intake frequencies than WWH (P values < 0.05). In WWH, multivariable-adjusted models indicated higher odds of NP impairment with higher intake frequencies of processed meat [P = 0.006; ORupper tertile = 1.91 (95% CI: 1.23-2.95; P = 0.003); ORmiddle tertile = 1.66 (95% CI: 1.14-2.42; P = 0.01)], sweet beverages [P = 0.02; ORupper tertile = 1.75 (95% CI: 1.17-2.64; P = 0.007)], fish [P = 0.01; ORupper tertile = 1.70 (95% CI: 1.10-2.64; P = 0.02)], and whole milk [P = 0.029; ORupper tertile = 1.66 (95% CI: 1.14-2.42; P = 0.008)]. Lower odds of NP impairment [P = 0.005; ORupper tertile = 0.65 (95% CI: 0.45-0.95; P = 0.02); ORmiddle tertile = 0.42 (95% CI: 0.24-0.73; P = 0.002)] were associated with higher vegetable intakes. In HIV-seronegative women, multivariable-adjusted models did not show associations between food line items/diet quality score and NP outcomes.ConclusionsIntakes of processed meat, sweet beverages, whole milk, fish, and vegetables may be associated with NP functions among WWH. Associations among WWH are not directly comparable to those among HIV-seronegative women, because models were conducted on each group separately given controls for HIV-specific covariates in WWH. Further studies are needed using more rigorous dietary assessment methods and lengthier longitudinal follow-ups