Multicenter AIDS Cohort Study Research Articles

Associations between epicardial, visceral and subcutaneous adipose tissue with diastolic function in men with and without HIV.

People with HIV (PWH) are at greater risk for diastolic dysfunction (DD) compared to persons without HIV (PWOH). An increase in visceral adipose tissue (AT) is common among PWH and greater visceral AT is associated with DD among PWOH. We investigated associations of visceral AT, subcutaneous AT and other fat depots with subclinical DD among men with and without HIV (MWH/MWOH). Cross-sectional analysis of MWH and MWOH in the Multicenter AIDS Cohort Study (MACS). Participants underwent echocardiography for DD assessment and CT scanning including subcutaneous, visceral, epicardial, and liver adiposity measurements. DD was defined by Characterizing Heart Function on Antiretroviral Therapy criteria. Odds for DD with each measure of adiposity were estimated using multivariable logistic regression. Among 403 participants (median age 57, 55% white, median BMI 26 kg/m2), 25% met criteria for DD and 59% MWH (82% undetectable plasma HIV RNA). Greater epicardial AT area was associated with higher odds of DD (odds ratio:1.54 per SD;95%CI:1.15-2.05) when adjusted for demographics, HIV serostatus, and cardiovascular risk factors. This association did not differ by HIV serostatus and persisted when excluding MWH who were not virally suppressed. Less subcutaneous AT was associated with a higher odds of DD. Other adipose depots were not associated with DD. Greater epicardial AT and less subcutaneous AT were associated with DD, regardless of HIV serostatus and viral suppression. Greater epicardial AT and less subcutaneous AT observed among PWH may contribute to risk for heart failure with preserved ejection fraction in this population.

Vision Problems As a Contributor to Lower Engagement in Care Among Aging Men Living with HIV

ABSTRACT Purpose To investigate vision impairment as a barrier to engagement in medical care among aging persons living with HIV (PLWH) who experience multimorbidity and complex care needs. Setting Multicenter AIDS Cohort Study (MACS), a prospective observational cohort of aging PLWH men. Methods We examined relationships of self-reported vision difficulty with indicators of care engagement: 1) adherence to HIV antiretroviral therapy (ART; defined as taking ≥95% of medications); 2) self-reported avoidance of medical care; 3) self-reported tendency to ask a doctor questions about care (>2 questions at a medical visit), as well as with quality of life. A modified version of the National Eye Institute Vision Function Questionnaire was administered at three semi-annual visits (from October 2017 to March 2019) to assess difficulty performing vision-dependent tasks. Results We included 1063 PLWH (median age 57 years, 31% Black). Data on care engagement outcomes were analyzed using repeated measures logistic regression with generalized estimating equations adjusted for race, and at visit values for age, education level, depressive symptoms, alcohol use, and smoking status. Compared to no vision difficulty, those reporting moderate to extreme vision difficulty on at least one task had 2.2 times higher odds (95% CI: 1.4, 3.4) of having less than optimal ART adherence, 1.9 times higher odds (95% CI: 1.1, 3.4) of avoiding necessary medical care and median quality of life scores 8 points lower. Conclusion These findings suggest vision impairment decreases medical care engagement including HIV care and quality of life among aging PLWH.

Longitudinal Analysis of Overlapping Psychosocial Factors Predicting Incident Hospitalization Among Mixed HIV Serostatus Men who have Sex with Men in the Multicenter AIDS Cohort Study.

Men who have sex with men (MSM) are at increased risk for certain types of chronic diseases and mental health problems. Despite having extended survival in the highly active antiretroviral therapy (HAART) era, MSM living with HIV contend with aging-related diseases and complications with treatment. Consequent hospitalizations incur high costs, fear, low quality of life, and frailty. Unlike heterosexual men, MSM experience more structural violence and "syndemics" of psychosocial factors that not only accelerate HIV acquisition and transmission risk but also may increase morbidity, leading to greater rates of hospitalization. We aim to examine the impact of "syndemic" psychosocial factors on the incidence of hospitalization among geographically diverse MSM in the US. Participants were 1760 MSM from the Multicenter AIDS Cohort Study (MACS) between 2004 and 2019. We examined the relationship between six psychosocial factors (depression, stimulant use, smoking, heroin use, childhood sexual abuse, and intimate partner violence) and incident hospitalization (admission to a hospital for treatment). We found a positive dose-response relationship between the number of syndemic factors and hospitalization. MSM reporting five or more syndemic factors had over twice the risk of hospitalization compared to MSM without syndemic factors [aRR = 2.14 (95% CI = 1.56, 2.94)]. Psychosocial factors synergistically increased hospitalizations over time. The positive dose-response relationship between the number of syndemic factors and hospitalization and the synergistic effects of these factors underscore the need for interventions that disentangle the syndemics to reduce hospitalization and related costs and improve the quality of life among MSM.

Metabolic and inflammatory perturbation of diabetes associated gut dysbiosis in people living with and without HIV infection

BackgroundGut dysbiosis has been linked with both HIV infection and diabetes, but its interplay with metabolic and inflammatory responses in diabetes, particularly in the context of HIV infection, remains unclear.MethodsWe first conducted a cross-sectional association analysis to characterize the gut microbial, circulating metabolite, and immune/inflammatory protein features associated with diabetes in up to 493 women (~ 146 with prevalent diabetes with 69.9% HIV +) of the Women’s Interagency HIV Study. Prospective analyses were then conducted to determine associations of identified metabolites with incident diabetes over 12 years of follow-up in 694 participants (391 women from WIHS and 303 men from the Multicenter AIDS Cohort Study; 166 incident cases were recorded) with and without HIV infection. Mediation analyses were conducted to explore whether gut bacteria–diabetes associations are explained by altered metabolites and proteins.ResultsSeven gut bacterial genera were identified to be associated with diabetes (FDR-q < 0.1), with positive associations for Shigella, Escherichia, Megasphaera, and Lactobacillus, and inverse associations for Adlercreutzia, Ruminococcus, and Intestinibacter. Importantly, the associations of most species, especially Adlercreutzia and Ruminococcus, were largely independent of antidiabetic medications use. Meanwhile, 18 proteins and 76 metabolites, including 3 microbially derived metabolites (trimethylamine N-oxide, phenylacetylglutamine (PAGln), imidazolepropionic acid (IMP)), 50 lipids (e.g., diradylglycerols (DGs) and triradylglycerols (TGs)) and 23 non-lipid metabolites, were associated with diabetes (FDR-q < 0.1), with the majority showing positive associations and more than half of them (59/76) associated with incident diabetes. In mediation analyses, several proteins, especially interleukin-18 receptor 1 and osteoprotegerin, IMP and PAGln partially mediate the observed bacterial genera–diabetes associations, particularly for those of Adlercreutzia and Escherichia. Many diabetes-associated metabolites and proteins were altered in HIV, but no effect modification on their associations with diabetes was observed by HIV.ConclusionAmong individuals with and without HIV, multiple gut bacterial genera, blood metabolites, and proinflammatory proteins were associated with diabetes. The observed mediated effects by metabolites and proteins in genera–diabetes associations highlighted the potential involvement of inflammatory and metabolic perturbations in the link between gut dysbiosis and diabetes in the context of HIV infection.

Incident Proteinuria differs by HIV Serostatus among Men with Pre-diabetes: The Multicenter AIDS Cohort Study.

Pre-diabetes is associated with proteinuria, a risk factor for chronic kidney disease. While people living with HIV (PWH) have a higher risk of proteinuria than people without HIV (PWOH), it is unknown whether incident proteinuria differs by HIV serostatus among pre-diabetic persons. Urine protein-to-creatinine ratio (PCR) was measured at semi-annual visits among men in the Multicenter AIDS Cohort Study since April 2006. Men with pre-DM on or after April 2006 and no prevalent proteinuria or use of anti-diabetic medications were included. Pre-diabetes was defined as fasting glucose (FG) of 100-125 mg/dL confirmed within a year by a repeat FG or hemoglobin A1c 5.7-6.4%. Incident proteinuria was defined as PCR > 200 mg/g, confirmed within a year. We used Poisson regression models to determine whether incident proteinuria in participants with pre-diabetes differed by HIV serostatus and, among PWH, whether HIV-specific factors were related to incident proteinuria. Between 2006 and 2019, among 1276 men with pre-diabetes, 128/613 PWH (21%) and 50/663 PWOH (8%) developed proteinuria over a median 10-year follow-up. After multivariable adjustment, the incidence of proteinuria in PWH with pre-diabetes was 3.3 times [95% CI: 2.3-4.8 times] greater than in PWOH (p < 0.01). Among PWH, current CD4 count <500 cells/mm3 (p < 0.01) and current use of protease inhibitors (p = 0.03) were associated with incident proteinuria, while lamivudine and integrase inhibitor use were associated with a lower risk. Among men with pre-DM, the risk of incident proteinuria was 3 times higher in PWH. Strategies to preserve renal function are needed in this population.

Shorter total sleep time is associated with lower CD4+/CD8+ T cell ratios in virally suppressed men with HIV.

Although poor sleep quality is associated with lower CD4+ T cell counts among people living with HIV (PLWH), the association between objective sleep metrics and T lymphocyte subset counts is unknown. We evaluated the association between polysomnography (PSG) derived sleep metrics and T lymphocyte subpopulations in a cohort of men living with HIV. Virally suppressed men living with HIV participating in the Multicenter AIDS Cohort Study underwent home overnight PSG. We assessed the association of PSG parameters with CD4+ and CD8+ T cell counts and the CD4+/CD8+ T cell ratio. Overall, 289 men with mean (±SD) age 55.3 ± 11.3 years and mean CD4+ T cell count 730 ± 308 cells/mm3 were evaluated. Total sleep time (TST) was significantly associated with CD8+ but not CD4+ T cell counts. After adjusting for age, race, depressive symptoms, antidepressant use, and non-nucleoside reverse transcriptase inhibitors use, every hour of shorter TST was associated with an additional 33 circulating CD8+ T cells/mm3 (p = 0.05) and a 5.6% (p = 0.0007) decline in CD4+/CD8+ T cell ratio. In adjusted models, every hour of shorter rapid eye movement (REM) sleep was associated with an additional 113 CD8+ T cells/mm3 (p = 0.02) and a 15.1% lower CD4+/CD8+ T cell ratio (p = 0.006). In contrast, measures of sleep efficiency and sleep-disordered breathing were not associated with differences in T lymphocyte subpopulations. Our findings suggest that shorter TST and REM sleep durations are associated with differences in T lymphocyte subpopulations among men living with HIV. Addressing sleep may reflect a novel opportunity to improve immune function in PLWH.

MOVEMENT AND HEALTH: NOVEL INSIGHTS INTO PHYSICAL ACTIVITY, ENERGY EXPENDITURE, AND MOTOR FUNCTION

Abstract Physical activity, energy expenditure, and motor function are well-established predictors of health and longevity with aging. Traditionally, most research using these measures has focused on speed of movement and intensity of activity. More recently, interest has grown in ways to refine these movement-related measures—and the methods used to analyze them—to improve predictive and discriminatory power for older adult health outcomes. This symposium will focus on measures derived from traditional in-lab assessments of motor function as well as free-living accelerometry, and their novel application across a variety of large U.S. cohort studies. Ms. Marino will present analyses on the links among heart rate variability, physical activity, and cognitive health in the Atherosclerosis Risk in Communities (ARIC) study. Dr. Dougherty will present the association of fine and gross motor function with MRI-derived brain volumes in the Baltimore Longitudinal Study of Aging (BLSA). Dr. Davoudi will present evidence on the link between physical activity quantities and variability with dementia in the National Health and Aging Trends Study (NHATS). Dr. Schumacher will compare measures of absolute and relative physical activity intensity with incident cardiovascular outcomes and all-cause mortality in the Objective Physical Activity and Cardiovascular Health (OPACH) Study. Finally, Dr. Wanigatunga will describe objectively measured physical activity quantities and patterns by self-reported fatigue levels and HIV status in the Multicenter AIDS Cohort Study (MACS). Collectively, these presentations will highlight novel ways to utilize motor function, energy expenditure, and physical activity data to advance prevention science and promote healthy aging. \ This is an Epidemiology of Aging Interest Group Sponsored Symposium.

The Relationship Between Posttraumatic Stress Disorder and Alcohol Misuse and Smoking Among Aging Men Who Have Sex With Men: No Evidence of Exercise or Volunteering Impact.

To determine if the association between posttraumatic stress disorder (PTSD) and substance use (alcohol misuse or smoking tobacco) is mediated/moderated by exercise or volunteering among aging (≥40years) men who have sex with men (MSM), and if this mediation/moderation differs by HIV serostatus. Multicenter AIDS Cohort Study data were used. Three datasets with PTSD measured during different time periods (10/1/2017-3/31/2018, 898 men; 4/1/2018-9/30/2018, 890 men; 10/1/2018-3/31/2019, 895 men) were analyzed. Longitudinal mediation analyses estimated the mediation effect of exercise and volunteering on the outcomes. Nine percent of MSM had evidence of PTSD. There was no statistically significant mediation effect of exercise or volunteering regardless of substance use outcome. The odds of smoking at a future visit among MSM with PTSD were approximately double those of MSM without PTSD. Results did not differ by HIV serostatus. There is a particular need for effective smoking cessation interventions for aging MSM with PTSD.

Loneliness and Frailty Among Middle-Aged and Aging Sexual Minority Men Living With or Without HIV: A Longitudinal Cross-Lagged Panel Analysis.

Loneliness is associated with frailty among older adults (60+), and there is evidence suggesting that this association may be bidirectional. However, there is limited evidence of this relationship over time among middle-aged and aging sexual minority men. We explored the bidirectional relationship between loneliness and frailty over 2 years among sexual minority men living with or without human immunodeficiency virus (HIV) from the Healthy Aging substudy of the Multicenter AIDS Cohort Study. We used data from 1 118 men (561 living with HIV; 557 living without HIV) aged 40 years or older with measurement of frailty or loneliness at Times 1 (September 2016 to March 2017) and 2 (September 2018 to March 2019). Descriptive statistics were generated. We used autoregressive cross-lagged panel analysis to examine the bidirectional association between frailty and loneliness at both time points while adjusting for time-stable and time-dependent covariates at Time 1. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were generated. The estimated prevalence of loneliness at both time points was 35.5%. The estimated prevalence of frailty at Times 1 and 2 were 7.8% and 12.1%, respectively. Participants reporting loneliness at Time 1 had greater odds of being frail at Time 2 (aOR = 2.14; 95% CI: 1.23-3.73). Frailty at Time 1 was not associated with loneliness at Time 2 (aOR = 1.00; 95% CI: .44-2.25). The autoregressive effects of frailty (aOR = 23.43; 95% CI: 11.94-46) and loneliness (aOR = 13.94; 95% CI: 9.42-20.61) were large. Men who felt lonely had higher odds of being frail 2 years later while the reciprocal association was not shown. This suggests that loneliness preceded frailty and not the other way around. Early and frequent assessments of loneliness may present opportunities for interventions that minimize the risk of frailty among sexual minority men living with and without HIV.

Relationship among serum levels of IL-6, sIL-6R, s gp130 and CD126 on T-cell in HIV-1 infected and uninfected men participating in the Los Angeles Multi-Center AIDS Cohort Study.

Interleukin 6 (IL-6) activates cells through its unique heterodimeric signaling complex of IL-6 receptor (IL6R) subunit and interleukin 6 signal transducer β-subunit glycoprotein 130 (gp130). The objective of this study was to investigate associations among serum levels of IL-6, sIL-6R, sgp130 and relative fluorescence intensity (RFI) of the α-subunit of the IL-6 receptor (CD126) on T-cells of HIV-1 infected and uninfected men. Blood samples were obtained from 69 HIV-1-infected men on Highly Active Antiretroviral Therapy (HAART) with mean age of 49.1 and 52 HIV-1-uninfected with mean age of 54.3 years -. All men were participating in the Los Angeles Multi-Center AIDS Cohort Study (MACS). Serum levels of IL-6, sIL-6R, sgp130 were measured by enzyme-linked immunoassays and T-cell phenotypic analysis and RFI of CD126 on CD4+ and CD8+ by flow cytometry. Mean serum levels of IL-6, sIL6R, sgp130 and of CD126 RFI on CD4+ were 4.34 pg/mL, 39.3 ng/mL, 349 ng/mL and 526 RFI respectively for HIV-1-infected men and 2.74 pg/mL, 41.9 ng/mL, 318 ng/mL and 561 RFI respectively for HIV-1-uninfected men. The mean serum concentrations of IL-6, sIL-6R in HIV-1-infected and uninfected men were not significantly different (p>0.05). There was a positive correlation between plasma HIV-1 RNA and the levels of IL-6 (p<0.001), sIL6R (p = 0.002) but no correlation with sgp130 (p = 0.339). In addition, there was a negative correlation between serum levels of IL-6 with RFI of CD126 on CD4+ (p = 0.037) and a positive correlation between serum levels of sgp130 (p = 0.021) and sIL-6R in HIV-1-infected men. Knowledge of biological variation, differences in the blood levels of biomarkers among healthy individuals and individuals experiencing illness, are very important for selection of appropriate tests for stage and progression of disease. Our data suggest no correlation among IL-6, and sIL-R6, in the treated phase of HIV-1 infection. The action and blood level of IL-6 and its receptors may be different at each stage of a disease progression.

Self-Perception of Aging and Hypertension in a Cohort of Sexual Minority.

Objectives To determine whether self-perception of aging is an important marker of health and hypertension among older sexual minority men. Methods We evaluated associations between self-perception of aging (chronologic-subjective age discrepancy and aging satisfaction) and hypertension among 1,180 sexual minority men (51.6% with HIV/48.4% without HIV) from the Multicenter AIDS Cohort Study using a manifest Markov chain model adjusted for HIV status, age, race/ethnicity, education, smoking status, inhaled nitrite use, diabetes, dyslipidemia, kidney and liver disease. Results The overall prevalence of hypertension increased from 73.1% to 82.6% over three years of follow-up. Older age discrepancy (aOR (adjusted odds ratio): 1.13 95% CI: 0.35-3.69) and low aging satisfaction (aOR: 0.88; 95% CI: 0.31-2.52) were not associated with an increased prevalence of hypertension, regardless of HIV status. Discussion More than 80% of sexual minority men had a diagnosis of hypertension but self-perception of aging was not predictive of incident hypertension.

Aging-Related Comorbidity Burden Among Women and Men With or At-Risk for HIV in the US, 2008-2019

Despite aging-related comorbidities representing a growing threat to quality-of-life and mortality among persons with HIV (PWH), clinical guidance for comorbidity screening and prevention is lacking. Understanding comorbidity distribution and severity by sex and gender is essential to informing guidelines for promoting healthy aging in adults with HIV. To assess the association of human immunodeficiency virus on the burden of aging-related comorbidities among US adults in the modern treatment era. This cross-sectional analysis included data from US multisite observational cohort studies of women (Women's Interagency HIV Study) and men (Multicenter AIDS Cohort Study) with HIV and sociodemographically comparable HIV-seronegative individuals. Participants were prospectively followed from 2008 for men and 2009 for women (when more than 80% of participants with HIV reported antiretroviral therapy use) through last observation up until March 2019, at which point outcomes were assessed. Data were analyzed from July 2020 to April 2021. HIV, age, sex. Comorbidity burden (the number of total comorbidities out of 10 assessed) per participant; secondary outcomes included individual comorbidity prevalence. Linear regression assessed the association of HIV status, age, and sex with comorbidity burden. A total of 5929 individuals were included (median [IQR] age, 54 [46-61] years; 3238 women [55%]; 2787 Black [47%], 1153 Hispanic or other [19%], 1989 White [34%]). Overall, unadjusted mean comorbidity burden was higher among women vs men (3.4 [2.1] vs 3.2 [1.8]; P = .02). Comorbidity prevalence differed by sex for hypertension (2188 of 3238 women [68%] vs 2026 of 2691 men [75%]), psychiatric illness (1771 women [55%] vs 1565 men [58%]), dyslipidemia (1312 women [41%] vs 1728 men [64%]), liver (1093 women [34%] vs 1032 men [38%]), bone disease (1364 women [42%] vs 512 men [19%]), lung disease (1245 women [38%] vs 259 men [10%]), diabetes (763 women [24%] vs 470 men [17%]), cardiovascular (493 women [15%] vs 407 men [15%]), kidney (444 women [14%] vs 404 men [15%]) disease, and cancer (219 women [7%] vs 321 men [12%]). In an unadjusted model, the estimated mean difference in comorbidity burden among women vs men was significantly greater in every age strata among PWH: age under 40 years, 0.33 (95% CI, 0.03-0.63); ages 40 to 49 years, 0.37 (95% CI, 0.12-0.61); ages 50 to 59 years, 0.38 (95% CI, 0.20-0.56); ages 60 to 69 years, 0.66 (95% CI, 0.42-0.90); ages 70 years and older, 0.62 (95% CI, 0.07-1.17). However, the difference between sexes varied by age strata among persons without HIV: age under 40 years, 0.52 (95% CI, 0.13 to 0.92); ages 40 to 49 years, -0.07 (95% CI, -0.45 to 0.31); ages 50 to 59 years, 0.88 (95% CI, 0.62 to 1.14); ages 60 to 69 years, 1.39 (95% CI, 1.06 to 1.72); ages 70 years and older, 0.33 (95% CI, -0.53 to 1.19) (P for interaction = .001). In the covariate-adjusted model, findings were slightly attenuated but retained statistical significance. In this cross-sectional study, the overall burden of aging-related comorbidities was higher in women vs men, particularly among PWH, and the distribution of comorbidity prevalence differed by sex. Comorbidity screening and prevention strategies tailored by HIV serostatus and sex or gender may be needed.

Classification of Free-Living Body Posture with ECG Patch Accelerometers: Application to the Multicenter AIDS Cohort Study.

As health studies increasingly monitor free-living heart performance via ECG patches with accelerometers, researchers will seek to investigate cardio-electrical responses to physical activity and sedentary behavior, increasing demand for fast, scalable methods to process accelerometer data. We extend a posture classification algorithm for accelerometers in ECG patches when researchers do not have ground-truth labels or other reference measurements (i.e., upright measurement). Men living with and without HIV in the Multicenter AIDS Cohort study wore the Zio XT® for up to two weeks (n = 1,250). Our novel extensions for posture classification include (1) estimation of an upright posture for each individual without a reference upright measurement; (2) correction of the upright estimate for device removal and re-positioning using novel spherical change-point detection; and (3) classification of upright and recumbent periods using a clustering and voting process rather than a simple inclination threshold used in other algorithms. As no posture labels exist in the free-living environment, we perform numerous sensitivity analyses and evaluate the algorithm against labelled data from the Towson Accelerometer Study, where participants wore accelerometers at the waist. On average, 87.1% of participants were recumbent at 4am and 15.5% were recumbent at 1pm. Participants were recumbent 54 minutes longer on weekends compared to weekdays. Performance was good in comparison to labelled data in a separate, controlled setting (accuracy = 96.0%, sensitivity = 97.5%, specificity = 95.9%). Posture may be classified in the free-living environment from accelerometers in ECG patches even without measuring a standard upright position. Furthermore, algorithms that fail to account for individuals who rotate and re-attach the accelerometer may fail in the free-living environment.

Study Protocol Using Cohort Data and Latent Variable Modeling to Guide Sampling Women With Type 2 Diabetes and Depressive Symptoms.

Depression affects one in three women with Type 2 diabetes, and this concurrence significantly increases the risks of diabetes complications, disability, and early mortality. Depression is underrecognized because of wide variation in presentation and the lack of diagnostic biomarkers. Converging evidence suggests inflammation is a shared biological pathway in diabetes and depression. Overlapping epigenetic associations and social determinants of diabetes and depression implicate inflammatory pathways as a common thread. This article describes the protocol and methods for a pilot study aimed to examine associations between depressive symptoms, inflammation, and social determinants of health among women with Type 2 diabetes. This is an observational correlational study that leverages existing longitudinal data from the Women's Interagency HIV Study (WIHS), a multicenter cohort of HIV seropositive (66%) and HIV seronegative (33%) women, to inform purposive sampling of members from latent subgroups emergent from a prior retrospective cohort-wide analysis. Local active cohort participants from the Bronx study site are then selected for the study. The WIHS recently merged with the Multicenter Aids Cohort Study (MACS) to form the MACS/WIHS Combined Cohort Study. Latent subgroups represent distinct symptom trajectories resultant from a growth mixture model analysis of biannually collected depressive symptom data. Participants complete surveys (symptom and social determinants) and provide blood samples to analyze plasma levels and DNA methylation of genes that encode for inflammatory markers (CRP, IL-6, TNF-α). Correlation and regression analysis will be used to estimate the effect sizes between depressive symptoms and inflammatory markers, clinical indices (body mass index, hemoglobin A1C, comorbidities), and social determinants of health. The study began in January 2022, and completed data collection is estimated by early 2023. We hypothesize that depressive symptom severity will associate with higher levels of inflammation, clinical indices (e.g., higher hemoglobin A1C), and exposure to specific social determinants of health (e.g., lower income, nutritional insecurity). Study findings will provide the basis for future studies aimed at improving outcomes for women with Type 2 diabetes by informing the development and testing of precision health strategies to address and prevent depression in populations most at risk.

Association Between Physical Activity and Psychosocial Resilience Among Middle-Aged and Aging Men Living With or Without HIV in the Multicenter AIDS Cohort Study

Introduction Increased resilience has been consistently linked to improved mental and physical health outcomes. Because individuals with HIV have a longer life expectancy than ever before, it is imperative to identify mechanisms to promote resilience in this population. Physical activity has significant potential to strengthen resilience and improve overall well-being in individuals with HIV. The goal of this study was to investigate whether increased physical activity is positively associated with increased individual-level psychosocial resilience, and whether this association varied by HIV status. Methods Data for this analysis were obtained from the Multicenter AIDS Cohort Study (MACS), a longitudinal observational cohort study following men living with and without HIV in the United States. Specifically, cross-sectional data collected between October 2016 and March 2017 from 1118 MACS participants enrolled in the Understanding Patterns of Healthy Aging Among Men Who Have Sex With Men sub-study were used. Odds ratios were determined using logistic regression to examine the association of physical activity with psychosocial resilience (measured using the 14-item Resilience Scale). Results Among all MACS participants enrolled in the sub-study, both sufficient physical activity and health-enhancing physical activity were positively associated with high resiliency (odds ratio, 2.20 [95% CI, 1.36-3.56] and odds ratio, 3.72 [95% CI, 2.30-6.03], respectively). Among the participants with HIV, only health-enhancing physical activity was positively associated with high resiliency (odds ratio, 3.07 [95% CI, 1.54-6.14]). Conclusions At the level of individual patient care, physical activity has significant potential to improve health outcomes and strengthen resilience in individuals living with HIV.

Subjective Age and Health Care Avoidance Among Aging Men Living With or Without HIV

Introduction Negative aging perceptions have been shown to influence one’s health care–seeking behaviors; this relationship has not been studied among middle-aged and aging adults living with HIV. The current study uses data from the Multicenter AIDS Cohort Study (MACS) to investigate the association between subjective age and health care avoidance. Objective To examine the hypothesis that adults living with HIV who perceive themselves as older, after adjustment for covariates, would be more likely to avoid care than their HIV-negative counterparts who perceive themselves as older. Methods The MACS is a prospective study of more than 7000 sexual minority men living with and without HIV from 4 metropolitan US areas. The Understanding Patterns of Healthy Aging in Men Who Have Sex With Men sub-study of the MACS was conducted from April 2016 to March 2019. Current analyses use cross-sectional data on 1118 participants from this sub-study from October 2016 to March 2017. Logistic regression was used to produce odds ratios and 95% CIs examining the association between subjective age and health care avoidance. Covariates included age, HIV status, race and ethnicity, education, and comorbid conditions. Further analyses were conducted among persons living with HIV, which included CD4 counts and viral load detection as covariates. Results In the full sample and sample of people living with HIV, after adjustment for covariates, there was a positive association between older subjective age and health care avoidance and a negative association between younger subjective age and health care avoidance, albeit both not statistically significant. Living with HIV was positively associated with health care avoidance, but not statistically significant. Conclusions Future studies with larger sample sizes are needed to elucidate the significance of subjective age and health care avoidance. Aside from the pivotal role of health care avoidance, the field of HIV and aging may benefit from identifying other psychological, physiological, and behavioral mechanisms by which perceptions of aging influence health.

Addressing Disparities in the Propensity Score Distributions for Treatment Comparisons from Observational Studies

Propensity score (PS) based methods, such as matching, stratification, regression adjustment, simple and augmented inverse probability weighting, are popular for controlling for observed confounders in observational studies of causal effects. More recently, we proposed penalized spline of propensity prediction (PENCOMP), which multiply-imputes outcomes for unassigned treatments using a regression model that includes a penalized spline of the estimated selection probability and other covariates. For PS methods to work reliably, there should be sufficient overlap in the propensity score distributions between treatment groups. Limited overlap can result in fewer subjects being matched or in extreme weights causing numerical instability and bias in causal estimation. The problem of limited overlap suggests (a) defining alternative estimands that restrict inferences to subpopulations where all treatments have the potential to be assigned, and (b) excluding or down-weighting sample cases where the propensity to receive one of the compared treatments is close to zero. We compared PENCOMP and other PS methods for estimation of alternative causal estimands when limited overlap occurs. Simulations suggest that, when there are extreme weights, PENCOMP tends to outperform the weighted estimators for ATE and performs similarly to the weighted estimators for alternative estimands. We illustrate PENCOMP in two applications: the effect of antiretroviral treatments on CD4 counts using the Multicenter AIDS cohort study (MACS) and whether right heart catheterization (RHC) is a beneficial treatment in treating critically ill patients.

Longitudinal associations of relationship support and strain and internalized homophobia with mental health among middle-aged and older gay and bisexual men

Objectives: Mental health concerns (e.g. depression, anxiety) that negatively impact gay, bisexual, and other men who have sex with men (GBMSM) persist over the life course and into old age, but less is known about potential contributors to GBMSM’s mental health. Close relationships can be a source of risk or resilience from stress, exerting direct relationships on mental health, and may mediate well-established associations between minority stress and mental health. This study examined whether primary partner relationship support and strain were uniquely associated with, and mediated the association between internalized homophobia, and mental health among older GBMSM. Methods: GBMSM (N = 517, M age = 60) from the Multicenter AIDS Cohort Study, who were in primary relationships with men, provided self-report data at four timepoints. We used multilevel modeling to examine longitudinal associations among relationship support and strain and internalized homophobia with depression and anxiety. Results: Relationship strain, but not support, was positively associated with mental health concerns longitudinally. There was a significant, positive indirect effect of internalized homophobia on depression and anxiety through strain, but no support. Internalized homophobia was positively associated with relationship strain, which was positively associated with mental health symptoms longitudinally. Conclusions: Relationship strain was associated with depression and anxiety longitudinally among middle-aged and older GBMSM and mediated associations of internalized homophobia with mental health. The role of partner support warrants further investigation. Mental health interventions are critically needed for older GBMSM and, for partnered GBMSM, should include strategies for reducing relationship strain to foster well-being.

Prevalence and Predictors of Sleep-Disordered Breathing in Men Participating in the Multicenter AIDS Cohort Study

Data on the prevalence of sleep-disordered breathing (SDB) in people with HIV are limited. Moreover, whether the associations between SDB and age or BMI differ by HIV status is unknown. Is SDB more prevalent in men with HIV than those without HIV, and do the predictors of SDB differ between the two groups? Home polysomnography was used in the Multicenter AIDS Cohort Study to assess SDB prevalence in men with (n= 466; 92%virologically suppressed) and without (n= 370) HIV. SDB was defined using the oxygen desaturation index (ODI) and the apnea-hypopnea index (AHI), using four definitions:≥ 5 events/h based on an ODI with a 3%(ODI3) or 4%(ODI4) oxygen desaturation, or an AHI with a 3%oxygen desaturation or EEG arousal (AHI3a) or with a 4%oxygen desaturation (AHI4). SDB prevalence was similar in men with and without HIV using the ODI3 and AHI3a definitions. However, SDB prevalence was higher in men with than without HIV using the ODI4 (55.9%vs47.8%; P= .04) and the AHI4 definitions (57.9%vs50.4%; P= .06). Mild and moderate SDB were more common in men with than without HIV. Associations between SDB prevalence and age, race, and BMI were similar in men with and without HIV. Among men with HIV, viral load, CD4 cell count, and use of antiretroviral medications were not associated with SDB prevalence. SDB prevalence was high overall but greater in men with than without HIV using the ODI4 threshold definition. Efforts to diagnose SDB are warranted in people with HIV, given that SDB is associated with daytime sleepiness and impaired quality of life.

Higher Soluble CD163 in Blood Is Associated With Significant Depression Symptoms in Men With HIV.

People with HIV (PWH) are more likely to experience depression, a highly morbid disease. More evidence is needed to better understand mechanisms of depression in PWH. We evaluated a panel of blood biomarkers in relation to depression symptoms in the Multicenter AIDS Cohort Study (MACS). Four sites in the United States. A cross-sectional analysis was performed within the MACS, a prospective study of cisgender men with and without HIV. Depression was assessed with the Center for Epidemiological Studies-Depression Scale, and six blood biomarkers were measured: GlycA, high sensitivity C-reactive protein (CRP), interleukin-6, CCL2, soluble CD14 (sCD14), and soluble CD163 (sCD163). Using univariable and multivariable logistic regression, the biomarkers and other factors were evaluated in relation to significant depression symptoms (SDS) by Center for Epidemiological Studies-Depression score ≥16. 784 men were analyzed; most of whom (63%) were PWH. PWH weremore likely to have SDS (32% vs. 21%). In univariable analysis, higher GlycA, CRP, and sCD163 concentrations were associated with SDS. In multivariable analysis, however, only higher sCD163 concentration was associated with SDS (odds ratio = 2.30, 95% CI = 1.11 to 4.76). This relationship was driven by the PWH group (odds ratio = 2.72, 95% CI = 1.12 to 6.58) and remained significant when controlling for antidepressant use. Lack of college education was also associated with SDS. Higher sCD163, a marker of macrophage activation, was significantly associated with significant depression symptoms in the MACS. Further research on this biomarker and macrophage activation in general is warranted to better understand and treat depression in PWH.