Search

The development of persistent cellular reservoirs of latent human immunodeficiency virus (HIV) is a critical obstacle to viral eradication since viral rebound takes place once anti-retroviral therapy (ART) is interrupted. Previous studies show that HIV persists in myeloid cells (monocytes and macrophages) in blood and tissues in virologically suppressed people with HIV (vsPWH). However, how myeloid cells contribute to the size of the HIV reservoir and what impact they have on rebound after treatment interruption remain unclear. Here we report the development of a human monocyte-derived macrophage quantitative viral outgrowth assay (MDM-QVOA) and highly sensitive T cell detection assays to confirm purity. We assess the frequency of latent HIV in monocytes using this assay in a longitudinal cohort of vsPWH (n = 10, 100% male, ART duration 5–14 yr) and find half of the participants showed latent HIV in monocytes. In some participants, these reservoirs could be detected over several years. Additionally, we assessed HIV genomes in monocytes from 30 vsPWH (27% male, ART duration 5–22 yr) utilizing a myeloid-adapted intact proviral DNA assay (IPDA) and demonstrate that intact genomes were present in 40% of the participants and higher total HIV DNA correlated with reactivatable latent reservoirs. The virus produced in the MDM-QVOA was capable of infecting bystander cells resulting in viral spread. These findings provide further evidence that myeloid cells meet the definition of a clinically relevant HIV reservoir and emphasize that myeloid reservoirs should be included in efforts towards an HIV cure.

Modern antiretroviral therapy (ART) has increased longevity of people with HIV and shifted the age distribution of the HIV pandemic upward toward that of the general population. This positive development has also led to concerns about premature and/or accelerated neurocognitive and physical ageing due to the combined effects of chronic HIV, accumulating comorbidities, adverse effects or possible toxicities of ART and biological ageing. Here we present results of comprehensive assessments over 12 years of 402 people with HIV in the CNS HIV ART Effects Research (CHARTER) programme, who at follow-up were composed of younger ( Over the 12 years, ART use and viral suppression increased in both subgroups as did systemic and psychiatric comorbidities; participants in both subgroups also evidenced neurocognitive decline beyond what is expected in typical ageing. Contrary to expectations, all these adverse effects were comparable in the younger and older CHARTER subgroups, and unrelated to chronological age. Neurocognitive decline was unrelated to HIV disease or treatment characteristics but was significantly predicted by the presence of comorbid conditions, specifically diabetes, hypertension, chronic pulmonary disease, frailty, neuropathic pain, depression and lifetime history of cannabis use disorder. These results are not consistent with premature or accelerated neurocognitive ageing due to HIV itself but suggest important indirect effects of multiple, potentially treatable comorbidities that are more common among people with HIV than in the general population. Good medical management of HIV disease did not prevent these adverse outcomes, and increased attention to a range of comorbid conditions in people with HIV may be warranted in their care.

Background Neurofilament light (NFL) chain concentrations, reflecting axonal damage, are seen in several polyneuropathies but have not been studied in human immunodeficiency virus (HIV) distal sensory polyneuropathy (DSP). We evaluated NFL in cerebrospinal fluid (CSF) and plasma in relation to DSP in people with HIV (PWH) from 2 independent cohorts and in people without HIV (PWoH). Methods Cohort 1 consisted of PWH from the CHARTER Study. Cohort 2 consisted of PWH and PWoH from the HIV Neurobehavioral Research Center (HNRC). We evaluated DSP signs and symptoms in both cohorts. Immunoassays measured NFL in CSF for all and for plasma as well in Cohort 2. Results Cohort 1 consisted of 111 PWH, mean ± SD age 56.8 ± 8.32 years, 15.3% female, 38.7% Black, 49.6% White, current CD4+ T-cells (median, interquartile range [IQR]) 532/µL (295, 785), 83.5% with plasma HIV RNA ≤50 copies/mL. Cohort 2 consisted of 233 PWH of similar demographics to PWH in Cohort 1 but also 51 PWoH, together age 58.4 ± 6.68 years, 41.2% female, 18.0% Black, Hispanic, non-Hispanic White 52.0%, 6.00% White. In both cohorts of PWH, CSF and plasma NFL were significantly higher in both PWH with DSP signs. Findings were similar, albeit not significant, for PWoH. The observed relationships were not explained by confounds. Conclusions Both plasma and CSF NFL were elevated in PWH and PWoH with DSP. The convergence of our findings with others demonstrates that NFL is a reliable biomarker reflecting peripheral nerve injury. Biomarkers such as NFL might provide, validate, and optimize clinical trials of neuroregenerative strategies in HIV DSP.

Task-evoked pupillary response (TEPR) is a measure of physiological arousal modulated by cognitive demand. Healthy individuals demonstrate greater TEPR prior to correct versus error antisaccade trials and correct antisaccade versus visually guided saccade (VGS) trials. The relationship between TEPR and antisaccade performance in individuals with psychotic disorders and their relatives has not been investigated. Probands with schizophrenia, schizoaffective disorder, psychotic bipolar disorder, their first-degree relatives, and controls from the B-SNIP study completed antisaccade and VGS tasks. TEPR prior to execution of responses on these tasks was evaluated among controls compared to probands and relatives according to diagnostic groups and neurobiologically defined subgroups (biotypes). Controls demonstrated greater TEPR on antisaccade correct versus error versus VGS trials. TEPR was not differentiated between antisaccade correct versus error trials in bipolar or schizophrenia probands, though was greater on antisaccade compared to prosaccade trials. There was no modulation of TEPR in schizoaffective probands. Relatives of schizophrenia and schizoaffective probands and those with elevated psychosis spectrum traits failed to demonstrate differential TEPR on antisaccade correct versus error trials. No proband or relative biotypes demonstrated differential TEPR on antisaccade correct versus error trials, and only proband biotype 3 and relative biotypes 3 and 2 demonstrated greater TEPR on antisaccade versus VGS trials. Our findings suggest that aberrant modulation of preparatory activity prior to saccade execution contributes to impaired executive cognitive control across the psychosis spectrum, including nonpsychotic relatives with elevated clinical risk. Reduced pupillary modulation under cognitive challenge may thus be a biomarker for the psychosis phenotype.

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.

Depression is common in people with HIV (PWH), yet little is known about the mechanisms contributing to depressive symptoms in PWH. Previous research across a range of populations has suggested a relationship between the neuropeptide oxytocin and depressive symptoms, with variable directionality. This article investigated the association between peripheral oxytocin levels and depressive symptoms in PWH.Unextracted oxytocin serum concentrations were assayed in 79 PWH (44% female, mean age = 34.35 [8.5], mean body mass index = 25.69 [5.46], mean CD4 = 516.60 [271.15]) who also completed the Center for Epidemiologic Studies Depression Scale (CES-D). CES-D items were evaluated in an exploratory factor analysis (EFA), and the relationships between oxytocin, total CES-D score, and the resulting EFA factors were analyzed with multivariate linear regressions conducted in R. Multiple regression models were used to adjust for age, sex, body mass index, CD4, and education.Contrary to hypothesized, higher peripheral oxytocin levels were associated with higher CES-D total scores with a small-to-moderate effect size ( β = 0.26, p = .009). Following Bonferroni correction, oxytocin was not significantly associated with any of the five factors identified from the EFA: depressed affect, positive affect, appetite, cognitive symptoms, or perceived failure ( p values.042). Small effect sizes were found for the depressed affect ( β = 0.22) and perceived failure ( β = 0.21) factors ( p values.042).In a sample of predominately Black or African American individuals with HIV, higher oxytocin was associated with higher total depressive symptoms. In addition, this relationship was slightly stronger than those of specific depressive symptoms. These findings warrant further study into the role of oxytocin in mood symptoms within PWH.

BACKGROUND: Aging in people with HIV is associated with increased risk of developing synergistic conditions such as neurocognitive impairment, polypharmacy, and falls. We assessed associations between polypharmacy (use of 5 or more non-ART medications), use of neurocognitive-adverse effects (NCAE) medications, and odds of falls in women with HIV (WWH) and without HIV (HIV−). METHODS: Self-reported falls and medication use data were contributed semiannually by 1872 (1315 WWH, 557 HIV−) Women’s Interagency HIV Study (WIHS) participants between 2014 and 2016. Polypharmacy and NCAE medication use were evaluated separately and jointly in multivariable models to assess their independent contributions to single and multiple falls risk. RESULTS: The proportion of women who reported any fall was similar by HIV status (19%). WWH reported both greater polypharmacy (51 % vs 41%; p

BACKGROUND Living with HIV is a risk factor for severe acute COVID-19, but it is unknown whether it is a risk factor for long COVID. OBJECTIVE This study aims to characterize symptoms, sequelae, and cognition formally and prospectively 12 months following SARS-CoV-2 infection in people living with HIV compared with people without HIV. People with no history of SARS-CoV-2 infection, both with and without HIV, are enrolled as controls. The study also aims to identify blood-based biomarkers or patterns of immune dysregulation associated with long COVID. METHODS This prospective observational cohort study enrolled participants into 1 of the following 4 study arms: people living with HIV who had SARS-CoV-2 infection for the first time RESULTS This project was funded in early 2021, and recruitment began in June 2021. Data analyses will be completed by summer 2023. As of February 2023, a total of 387 participants were enrolled in this study, with 345 participants having completed enrollment or baseline surveys together with at least one other completed study event. The 345 participants includes 76 (22%) HIV+COVID+, 121 (35.1%) HIV−COVID+, 78 (22.6%) HIV+COVID−, and 70 (20.3%) HIV−COVID− participants. CONCLUSIONS This study will provide longitudinal data to characterize COVID-19 recovery over 12 months in people living with and without HIV. Additionally, this study will determine whether biomarkers or patterns of immune dsyregulation associate with decreased cognitive function or symptoms of long COVID. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/47079

ObjectiveEarly life trauma (ELT) and HIV are associated with social processing deficits. In people with HIV (PWH), we examined whether facial emotion identification accuracy differs by ELT and whether neuroendocrine factors including cortisol, oxytocin (OT), and arginine vasopressin, and/or immune system measures play a role in the ELT-performance association.MethodsWe used secondary data from the placebo condition of a pharmacologic challenge study in PWH. Presence of ELT was measured with the Childhood Trauma Questionnaire (at least moderate experiences of sexual, physical, and/or emotional abuse). Social processing was measured with the Facial Emotion Perception Test (FEPT). Salivary immune system measures and cortisol were sampled across a 5-hour study session. Blood was collected at study session start (12 pm ) to measure OT and arginine vasopressin. We examined the association of ELT with FEPT and five biological moderators (from principal components analysis of 12 biomarkers) of ELT-FEPT associations.ResultsOf 58 PWH (42 men; mean [standard deviation] age = 33.7 [8.9] years), 50% endorsed ELT. ELT-exposed PWH demonstrated lower identification accuracy across all emotional expressions (unstandardized β [ B ] = 0.13; standard error [SE] = 0.05; p = .021, d = 0.63) and had higher OT levels compared with ELT-unexposed PWH ( t(1,56) = 2.12, p = .039; d = 0.57). For total accuracy, an OT/C-reactive protein factor moderated the ELT-FEPT association ( B = 0.14; SE = 0.05; p = .014); accuracy was lower in ELT-exposed PWH versus ELT-unexposed PWH when the factor was low but not when high. Similar results were obtained for fearful, neutral, and happy faces ( p values < .05). Regardless of ELT, a myeloid migration (MCP-1/MMP-9) factor was associated with reduced accuracy ( p values < .05).ConclusionsOur pilot findings suggest that ELT may alter social processing in PWH, and OT and C-reactive protein may be a target for improving social processing in ELT-exposed PWH, and myeloid migration markers may be a target in PWH more generally.

Simian immunodeficiency virus (SIV) infection of macaques recapitulates many aspects of HIV pathogenesis and is similarly affected by both genetic and environmental factors. Psychosocial stress is associated with immune system dysregulation and worse clinical outcomes in people with HIV. This study assessed the impact of single housing, as a model of psychosocial stress, on innate immune responses of pigtailed macaques ( Macaca nemestrina ) during acute SIV infection.A retrospective analysis of acute SIV infection of 2- to si6-year-old male pigtailed macaques was performed to compare the innate immune responses of socially ( n = 41) and singly ( n = 35) housed animals. Measures included absolute monocyte count and subsets, and in a subset ( n ≤ 18) platelet counts and activation data.SIV infection resulted in the expected innate immune parameter changes with a modulating effect from housing condition. Monocyte number increased after infection for both groups, driven by classical monocytes (CD14 + CD16 - ), with a greater increase in socially housed animals (227%, p.001, by day 14 compared with preinoculation time points). Platelet numbers recovered more quickly in the socially housed animals. Platelet activation (P-selectin) increased by 65% ( p = .004) and major histocompatibility complex class I surface expression by 40% ( p = .009) from preinoculation only in socially housed animals, whereas no change in these measures occurred in singly housed animals.Chronic psychosocial stress produced by single housing may play an immunomodulatory role in the innate immune response to acute retroviral infection. Dysregulated innate immunity could be one of the pathways by which psychosocial stress contributes to immune suppression and increased disease severity in people with HIV.

Alterations in glucocorticoid receptor (GCR) function may be a risk factor for cognitive complications among older people with human immunodeficiency virus (HIV). We evaluated whether HIV serostatus and age modify the GCR function-cognition association among women.Eighty women with HIV ( n = 40,40 years of age [younger]; n = 40,50 years of age [older]) and 80 HIV-uninfected women ( n = 40 older, n = 40 younger) enrolled in the Women's Interagency HIV Study completed a comprehensive neuropsychological test battery. Peripheral blood mononuclear cells collected concurrent with neuropsychological testing were assessed for GCR function. Multivariable linear regression analyses were conducted to examine whether a) HIV serostatus and age were associated with GCR function, and b) GCR function-cognition associations are moderated by HIV serostatus and age adjusting for relevant covariates.Among older women, higher baseline FKBP5 expression level was associated with lower attention/working memory performance among women with HIV ( B = 6.4, standard error = 1.7, p = .0003) but not in women without HIV infection ( B = -1.7, standard error = 1.9, p = .37). There were no significant HIV serostatus by age interactions on dexamethasone (DEX)-stimulated expression of the genes regulated by the GCR or lipopolysaccharide-stimulated tumor necrosis factor α levels (with or without DEX stimulation; p values.13). HIV serostatus was associated with GC target genes PER1 ( p = .006) and DUSP1 ( p = .02), but not TSC22D3 ( p = .32), after DEX stimulation.Collectively, these data suggest that HIV serostatus and age may modify the influence of the GCR, such that the receptor is likely engaged to a similar extent, but the downstream influence of the receptor is altered, potentially through epigenetic modification of target genes.

The number of people with HIV (PWH) experiencing age-associated comorbidities including those treated with medications and cognitive impairment is increasing. We examined associations between polypharmacy and cognition in older women with HIV (WWH) given their vulnerability to this comorbidity. Cross-sectional analysis capitalizing on Women's Interagency HIV Study data collected between 2014 and 2017. WWH meeting the following criteria were analyzed: age ≥50 years; availability of self-reported non-antiretroviral therapy (ART) medications data; and neuropsychological data. The number of non-ART medications used regularly in the prior 6 months was summed. Polypharmacy was categorized as none/low (0–4), moderate (5–9), or severe (≥10). Multivariable linear regression analyses examined polypharmacy-cognition (T-score) associations in the total sample and among virally suppressed (VS; < 20 copies/mL)-WWH after covariate adjustment for enrollment site, income, depressive symptoms, substance use (smoking, heavy alcohol, marijuana, crack, cocaine, and/or heroin), the Veterans Aging Cohort Study index (indicators of HIV disease and organ system function, hepatitis C virus serostatus), ART use, nadir CD4 count, and specific ART drugs (efavirenz, integrase inhibitors). We included 637 women (median age = 55 years; 72% Black). Ninety-four percent reported ART use in the past 6 months and 75% had HIV RNA

ObjectiveThe primary objective of this study was to evaluate the correlation of large mitochondrial DNA (mtDNA) deletions in skin samples of people with HIV (PWH) with measures of neuropathy and prior exposure to therapy. We hypothesized that deletions would be associated with neuropathy. As secondary objectives, we determined the correlation of deletion burden with demographic data and neuropathy measures.MethodsIn this retrospective cohort study, we measured the accumulation of large mtDNA deletions in skin biopsies from PWH recruited as part of the AIDS Clinical Trials Group (ACTG). Our cohort includes individuals with and without sensory neuropathy, as well as individuals with normal or abnormal skin biopsies. Skin biopsies, sural and peroneal nerve conduction studies, total neuropathy score, and deletion burden scores were measured, along with baseline demographic data such as age, CD4+ cell count, viral counts, and prior nucleoside reverse transcriptase inhibitor exposures.ResultsSixty-seven PWH were enrolled in the study. The mean age of the cohort (n = 67) was 44 years (SD 6.8, range 32–65 years), and 9 participants were female. The mean CD4+ T-cell count was 168 cells/mm3(SD 97 cells/mm3, range 1–416 cells/mm3) and mean viral load was 51,129 copies/mL (SD 114,586 copies/mL, range 147–657,775 copies/mL). We determined that there was a correlation between the total mtDNA deletion and intraepidermal nerve fiber density (IENFD) (r= −0.344,p= 0.04) and sural nerve amplitude (r= −0.359,p= 0.004).ConclusionsBoth IENFD and sural nerve amplitude statistically correlate with mitochondrial mutation burden in PWH, specifically in those with HIV-associated sensory neuropathy as assessed by skin biopsy.

Background Integrase strand transfer inhibitors (INSTIs) are first-line regimens for HIV treatment. We aimed to examine their impact on cognitive performance and depressive symptoms in women with HIV (WWH). Setting Women's Interagency HIV Study, a multisite, prospective, cohort study. Methods WWH who started or switched to INSTI-based antiretroviral therapy (ART) and completed neuropsychological testing and the Center for Epidemiological Studies-Depression (CES-D) scale before and after INSTI start/switch were included in the analyses. Primary outcomes were demographically corrected cognitive domain T-scores. Linear mixed-effects models adjusted for relevant covariates were used to examine effects of start/switch of any INSTI and individual INSTI drugs on cognition and CES-D scores. Results Six hundred thirty-nine WWH, median age 49 (interquartile range 12) years, 66% Black non-Hispanic, had neuropsychological and CES-D scale data before and after INSTI start/switch. Although 14% started INSTI-based ART, the remainder switched to INSTI-based ART from another regimen. Overall, any INSTI use was associated with poorer learning post-INSTI. Specifically, use of dolutegravir and elvitegravir, but not raltegravir, was associated with poorer learning. In analyses restricted to INSTI switch, any INSTI use, and dolutegravir use, was associated with poorer learning. Among those switching from a PI-based regimen, INSTIs overall and dolutegravir remained associated with poorer learning; switching from a nonnucleoside reverse transcriptase inhibitor to dolutegravir was also associated with poorer learning. INSTI start/switch was not related to depressive symptom changes. Conclusions INSTI use was associated with poorer learning among WWH. These changes were mainly observed in elvitegravir and dolutegravir users, indicating that the impact of INSTI on cognition in WWH may not be a class effect.

Background Living with HIV is a risk factor for severe acute COVID-19, but it is unknown whether it is a risk factor for long COVID. Objective This study aims to characterize symptoms, sequelae, and cognition formally and prospectively 12 months following SARS-CoV-2 infection in people living with HIV compared with people without HIV. People with no history of SARS-CoV-2 infection, both with and without HIV, are enrolled as controls. The study also aims to identify blood-based biomarkers or patterns of immune dysregulation associated with long COVID. Methods This prospective observational cohort study enrolled participants into 1 of the following 4 study arms: people living with HIV who had SARS-CoV-2 infection for the first time Results This project was funded in early 2021, and recruitment began in June 2021. Data analyses will be completed by summer 2023. As of February 2023, a total of 387 participants were enrolled in this study, with 345 participants having completed enrollment or baseline surveys together with at least one other completed study event. The 345 participants includes 76 (22%) HIV+COVID+, 121 (35.1%) HIV−COVID+, 78 (22.6%) HIV+COVID−, and 70 (20.3%) HIV−COVID− participants. Conclusions This study will provide longitudinal data to characterize COVID-19 recovery over 12 months in people living with and without HIV. Additionally, this study will determine whether biomarkers or patterns of immune dsyregulation associate with decreased cognitive function or symptoms of long COVID. International Registered Report Identifier (IRRID) DERR1-10.2196/47079

Human immunodeficiency virus (HIV) infection is potentially associated with premature aging, but demonstrating this is difficult due to a lack of reliable biomarkers. The mitochondrial (mt) DNA "common deletion" mutation (mtCDM) is a 4977-bp deletion associated with aging and neurodegenerative diseases. We examined how mtDNA and mtCDM correlate with markers of neurodegeneration and inflammation in people with and without HIV (PWH and PWOH). Data from 149 adults were combined from two projects involving PWH (n = 124) and PWOH (n = 25). We measured buccal mtDNA and mtCDM by digital droplet PCR and compared them to disease and demographic characteristics and soluble biomarkers in cerebrospinal fluid (CSF) and blood measured by immunoassay. Participants had a median age of 52years, with 53% white and 81% men. Median mtDNA level was 1,332 copies/cell (IQR 1,201-1,493) and median mtCDM level was 0.36 copies × 102/cell (IQR 0.31-0.42); both were higher in PWH. In the best model adjusting for HIV status and demographics, higher mtDNA levels were associated with higher CSF amyloid-β 1-42 and 8-hydroxy-2'-deoxyguanosine and higher mtCDM levels were associated with higher plasma soluble tumor necrosis factor receptor II. The differences in mtDNA markers between PWH and PWOH support potential premature aging in PWH. Our findings suggest mtDNA changes in oral tissues may reflect CNS processes, allowing the use of inexpensive and easily accessible buccal biospecimens as a screening tool for CSF inflammation and neurodegeneration. Confirmatory and mechanistic studies on mt genome alterations by HIV and ART may identify interventions to prevent or treat neurodegenerative complications.

Background and Objective Overweight and obesity influence cognitive health, and measured during midlife, may be associated with declining neuropsychological performance (NP) and late-onset dementia in older adults. Few studies have considered these associations in women living with HIV (WLWH). We examined associations cross-sectionally and up to 10 years longitudinally between body mass index (BMI) and waist circumference (WC) and NP in middle-aged WLWH and women without HIV (HIV-).Methods.BMI and WC were measured in 432 virologically-suppressed WLWH and 367 HIV- women, >40 years, who participated in the Women’s Interagency HIV Study (WIHS) and with NP assessments every two years from 2009-2019. Demographically-adjusted T-scores were calculated for six NP domains: learning, memory, executive function, processing speed, attention and working memory, and motor function. Multivariable linear regression models stratified by HIV serostatus were used to examine cross-sectional associations of BMI and WC with each NP domain; repeated measures analyses assessed baseline BMI and WC in association with longitudinal change in NP. Results were outputted as beta-coefficients (b) and 95% Confidence Intervals (95%CI). Covariates included sociodemographic, behavioral, and HIV-related characteristics.ResultsAt baseline, obese WLWH (BMI>30.0 kg/m2) had poorer executive function (β=-2.27, 95%CI [-4.46, -0.07], p=0.043) compared to normal (BMI 18.5–24.9 kg/m2). Longitudinally over ~8 years follow-up, obese versus overweight WLWH improved on learning (β=1.88, 95%CI [0.24, 3.51], p=0.025).Among HIV- women, an overweight versus normal BMI was associated with declining memory (β=-3.13, 95%CI [-5.75, -0.51], p=0.019); however, obese versus overweight HIV- women improved on memory (β=2.47, 95%CI [0.47, 4.46], p=0.015). Among HIV- women, increasing WC was associated with decreasing executive (β=-0.07, 95%CI [-0.11, -0.02], p=0.058), processing speed (β=-0.05, 95%CI [-0.10, -0.01], p=0.044), and motor (β=-0.05, 95%CI [-0.10, -0.01], p=0.033) performance during follow-up.ConclusionsCross-sectional and longitudinal associations of BMI and central adiposity and NP were mixed among WLWH and HIV- women during midlife. However, HIV- women may experience greater NP decline in association with higher adiposity compared to WLWH.

BACKGROUND: Neurocognitive impairment (NCI) persists among women living with HIV. Food insecurity is also common among women and may be an important modifiable contributor of NCI. OBJECTIVE: The goal of this study was to determine the association of food insecurity with neurocognitive function among women living with or without HIV. METHODS: From 2013 to 2015, we analyzed data from a cross-sectional sample from the Women's Interagency HIV Study (WIHS). Measures included food insecurity and a comprehensive neuropsychological test battery assessing executive function, processing speed, attention/working memory, learning, memory, fluency, and motor function. We conducted multivariable linear regressions to examine associations between food insecurity and domain-specific neurocognitive performance, adjusting for relevant sociodemographic, behavioral, and clinical factors. RESULTS: Participants (n = 1,324) were predominantly HIV seropositive (68%), Black/African-American (68%) or Hispanic (16%), and low income (48% reported

Elevations in peripheral inflammatory markers have been reported in patients with psychosis. Whether this represents an inflammatory process defined by individual or subgroups of markers is unclear. Further, relationships between peripheral inflammatory marker elevations and brain structure, cognition, and clinical features of psychosis remain unclear. We hypothesized that a pattern of plasma inflammatory markers, and an inflammatory subtype established from this pattern, would be elevated across the psychosis spectrum and associated with cognition and brain structural alterations. Clinically stable psychosis probands (Schizophrenia spectrum, n = 79; Psychotic Bipolar disorder, n = 61) and matched healthy controls (HC, n = 60) were assessed for 15 peripheral inflammatory markers, cortical thickness, subcortical volume, cognition, and symptoms. A combination of unsupervised exploratory factor analysis and hierarchical clustering was used to identify inflammation subtypes. Levels of IL6, TNFα, VEGF, and CRP were significantly higher in psychosis probands compared to HCs, and there were marker-specific differences when comparing diagnostic groups. Individual and/or inflammatory marker patterns were associated with neuroimaging, cognition, and symptom measures. A higher inflammation subgroup was defined by elevations in a group of 7 markers in 36% of Probands and 20% of HCs. Probands in the elevated inflammatory marker group performed significantly worse on cognitive measures of visuo-spatial working memory and response inhibition, displayed elevated hippocampal, amygdala, putamen and thalamus volumes, and evidence of gray matter thickening compared to the proband group with low inflammatory marker levels. These findings specify the nature of peripheral inflammatory marker alterations in psychotic disorders and establish clinical, neurocognitive and neuroanatomic associations with increased inflammatory activation in psychosis. The identification of a specific subgroup of patients with inflammatory alteration provides a potential means for targeting treatment with anti-inflammatory medications.