Transgender Women With Suppressed Testosterone Display Lower Burden of Coronary Disease Than Matched Cisgender Men.

Context: Cardiovascular disease (CVD) in transgender women (TW) may be affected by gender-affirming hormone therapy (GAHT) and HIV, but few data compare TW on contemporary GAHT to well-matched controls. Objective: We compared CVD burden and biomarker profiles between TW and matched cisgender men (CM). Methods: Adult TW on GAHT (n = 29) were recruited for a cross-sectional study (2018-2020). CM (n = 48) from the former Multicenter AIDS Cohort Study were matched 2:1 to TW on HIV serostatus, age ±5 years, race/ethnicity, BMI category and antiretroviral therapy (ART) type. Cardiac parameters were measured by CT and coronary atherosclerosis by coronary CT angiography; sex hormone and biomarker concentrations were measured centrally from stored samples. Results: Overall, median age was 53 years and BMI 29 kg/m2; 69% were non-white. All participants with HIV (71%) had viral suppression on ART. Only 31% of TW had testosterone suppression (<50 ng/dL, TW-S). Traditional CVD risk factors were similar between groups, except that TW-S had higher BMI than TW with non-suppressed testosterone (TW-T). TW-S had no evidence of non-calcified coronary plaque or advanced coronary stenosis, whereas TW-T and CM had similar burden. TW had lower prevalence of any coronary plaque, calcified plaque and mixed plaque than CM, regardless of testosterone concentrations and HIV serostatus. Estradiol but not testosterone concentrations moderately and negatively correlated with the presence of coronary plaque and stenosis. Small sample size limited statistical power. Conclusion: Older TW with suppressed total testosterone on GAHT had no CT evidence of non-calcified coronary plaque or advanced coronary stenosis. Longitudinal studies to understand relationships between GAHT and CVD risk in TW are needed.

Disrupting the Path from Depression to Loneliness: Multilevel Resilience among Older Sexual Minority Men with and without HIV.

Existing studies examining resilience among sexual minority men (SMM) have been limited by only analyzing 1 level of resilience. We therefore investigated the impact of multiple levels of resilience on the bidirectional relationship between loneliness and depression symptoms among older SMM. Loneliness, depression symptoms, and multilevel resilience scores were collected across 3 time points (October 2016 to March 2017 [T1]; October 2017 to March 2018 [T2]; and October 2018 to March 2019 [T3]) among 1,264 SMM aged 40 years and older living with and without HIV. Longitudinal mediation models were used to test the mediating effect of the multilevel resilience factors at T2 on the bidirectional relationship between loneliness and depression symptoms, adjusting for sociodemographic covariates. The multilevel resilience factors were negatively associated with loneliness and depression symptoms at T1. The individual-level global resilience factor was associated with decreased odds of depression symptoms (odds ratio [OR] = 0.50; 95% CI, 0.32-0.78), while the interpersonal-level relationship confidence (OR = 0.43; 95% CI, 0.24-0.77) and reliability (OR = 0.36; 95% CI, 0.15-0.84) factors were associated with decreased odds of loneliness at T3. The total effect of loneliness at T1 on depressive symptoms at T3 was ß = 0.20 (95% CI, 0.11-0.28) and was reduced to ß = 0.08 (95% CI, -0.04 to 0.20) after the inclusion of the multilevel resilience factors. The total effect of depressive symptoms at T1 on loneliness at T3 was similar (ß = 0.21; 95% CI, 0.13-0.28) with the direct effect of ß = 0.01 (95% CI, -0.08 to 0.11) after the inclusion of the multilevel resilience factors. Regarding specific indirect effects, individual-level global resilience (depression symptoms at T3 only) as well as the interpersonal-level relationship reliability and confidence (loneliness at T3 model only) factors were statistically significant. Multilevel resilience factors mediated the bidirectional relationship between loneliness and depression symptoms. Mental health interventions should consider implementing resilience-informed strategies that mitigate depression symptoms and loneliness among older SMM.

RESUMEN: Los estudios existentes que examinan la resiliencia entre los hombres de minorías sexuales (HSH) se han visto limitados por analizar sólo 1 nivel de resiliencia. Por lo tanto, investigamos el impacto de múltiples niveles de resiliencia en la relación bidireccional entre la soledad y los síntomas de depresión entre los hombres mayores de minorías sexuales. Se recopilaron datos sobre soledad, síntomas de depresión y resiliencia multinivel a lo largo de 3 puntos temporales (octubre de 2016 a marzo de 2017 [T1]; octubre de 2017 a marzo de 2018 [T2]; y octubre de 2018 a marzo de 2019 [T3]) entre 1,264 SMM de 40 años o más que viven con y sin VIH. Se utilizaron modelos de mediación longitudinal para probar el efecto mediador de los factores de resiliencia multinivel en T2 sobre la relación bidireccional entre la soledad y los síntomas de depresión, ajustando por covariables sociodemográficas. Los factores de resiliencia multinivel se asociaron negativamente con la soledad y los síntomas de depresión en T1. El factor de resiliencia global a nivel individual se asoció con menores probabilidades de síntomas de depresión (odds ratio [OR] = 0,50; IC 95%, 0,32 − 0,78), mientras que el factor de confianza en las relaciones a nivel interpersonal (OR = 0.43; 95% CI, 0.24­0.77) y los factores de fiabilidad (OR = 0.36; 95% CI, 0.15­0.84) se asociaron con menores probabilidades de soledad en T3. El efecto total de la soledad en T1 sobre los síntomas depresivos en T3 fue ß = 0.20 (95% CI, 0.11­0.28) y se redujo a ß = 0.08 (95% CI, -0.04 to 0.20) tras la inclusión de los factores de resiliencia multinivel. El efecto total de los síntomas depresivos en T1 sobre la soledad en T3 fue similar (ß = 0.21; 95% CI, 0.13­0.28) con el efecto directo de ß = 0.01 (95% CI, -0.08 to 0.11) tras la inclusión de los factores de resiliencia multinivel. En cuanto a los efectos indirectos específicos, los factores de resiliencia global a nivel individual (síntomas de depresión sólo en T3) así como la fiabilidad y confianza de las relaciones interpersonales (soledad en el modelo T3 solamente) fueron estadísticamente significativos. Los factores de resiliencia multinivel mediaron la relación bidireccional entre la soledad y los síntomas de depresión. Las intervenciones de salud mental deberían considerar la implementación de estrategias basadas en la resiliencia que mitiguen los síntomas de la depresión y la soledad entre los SMM mayores.

Does Resilience Mediate the Relationship Between Negative Self-Image and Psychological Distress in Middle-Aged and Older Gay and Bisexual Men?

Aging gay and bisexual men may have negative self-images due to body image dissatisfaction and internalized ageism, resulting in psychological distress. Gay and bisexual men with HIV may be at greater risk for distress because of research linking HIV to accelerated aging. We examined associations between self-image and psychological distress, and potential mediating effects (resilience, fitness engagement), and whether these relationships were moderated by HIV serostatus. We tested our hypotheses with structural equation modeling using data from gay and bisexual men with HIV (n = 525, Mage = 57.6) and without HIV (n = 501, Mage = 62.2). We observed significant positive associations between self-image and distress and significant mediation effects (resilience, fitness engagement) that were moderated by HIV serostatus (resilience was only significant for men with HIV). We conclude that resilience interventions may be beneficial in alleviating distress from negative self-image among aging gay and bisexual men with HIV.

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

BACKGROUND: People with HIV (PWH) are at greater risk for diastolic dysfunction compared with persons without HIV (PWOH). An increase in visceral adipose tissue is common among PWH and greater visceral adipose tissue is associated with diastolic dysfunction among PWOH. We investigated associations of visceral adipose tissue, subcutaneous adipose tissue, and other fat depots with subclinical diastolic dysfunction among men with and without HIV (MWH and MWOH). DESIGN: Cross-sectional analysis of MWH and MWOH in the Multicenter AIDS Cohort Study (MACS). METHODS: Participants underwent echocardiography for diastolic dysfunction assessment and CT scanning including subcutaneous, visceral, epicardial, and liver adiposity measurements. Diastolic dysfunction was defined by characterizing heart function on antiretroviral therapy0 criteria. Odds for diastolic dysfunction with each measure of adiposity were estimated using multivariable logistic regression. RESULTS: Among 403 participants (median age 57, 55% white, median BMI 26 kg/m 2 ), 25% met criteria for diastolic dysfunction and 59% MWH (82% undetectable plasma HIV RNA). Greater epicardial adipose tissue area was associated with higher odds of diastolic dysfunction [odds ratio:1.54 per SD; 95%confidence interval (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 adipose tissue was associated with higher odds of diastolic dysfunction. Other adipose depots were not associated with diastolic dysfunction. CONCLUSION: Greater epicardial adipose tissue and less subcutaneous adipose tissue were associated with diastolic dysfunction, regardless of HIV serostatus and viral suppression. Greater epicardial adipose tissue and less subcutaneous adipose tissue observed among PWH may contribute to risk for heart failure with preserved ejection fraction in this population.

Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection.

People living with HIV (PLWH) experience increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors associated with this vulnerability remain uncertain. In the general population, alterations in the N-glycans on IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG N-glycans in cross-sectional and longitudinal samples from 1214 women and men, living with and without HIV. PLWH exhibit an accelerated accumulation of pro-aging-associated glycan alterations and heightened expression of senescence-associated glycan-degrading enzymes compared to controls. These alterations correlate with elevated markers of inflammation and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit a reduced ability to elicit anti-HIV Fc-mediated immune activities. These findings hold potential for the development of biomarkers and tools to identify and prevent premature aging and comorbidities in PLWH.

Intersectional stigma and the non-communicable disease syndemic in the context of HIV: protocol for a multisite, observational study in the USA.

INTRODUCTION: The increasing burden of non-communicable diseases, such as hypertension, diabetes and dyslipidaemia, presents key challenges to achieving optimal HIV care outcomes among ageing people living with HIV. These diseases are often comorbid and are exacerbated by psychosocial and structural inequities. This interaction among multiple health conditions and social factors is referred to as a syndemic. In the USA, there are substantial disparities by social position (ie, racial, ethnic and socioeconomic status) in the prevalence and/or control of non-communicable diseases and HIV. Intersecting stigmas, such as racism, classism and homophobia, may drive these health disparities by contributing to healthcare avoidance and by contributing to a psychosocial syndemic (stress, depression, violence victimisation and substance use), reducing success along the HIV and non-communicable disease continua of care. Our hypothesis is that marginalised populations experience disparities in non-communicable disease incidence, prevalence and control, mediated by intersectional stigma and the psychosocial syndemic. METHODS AND ANALYSIS: Collecting data over a 4 year period, we will recruit sexual minority men (planned n=1800) enrolled in the MACS/WIHS Combined Cohort Study, a long-standing mixed-serostatus observational cohort in the USA, to investigate the following specific aims: (1) assess relationships between social position, intersectional stigma and the psychosocial syndemic among middle-aged and ageing sexual minority men, (2) assess relationships between social position and non-communicable disease incidence and prevalence and (3) assess relationships between social position and HIV and non-communicable disease continua of care outcomes, mediated by intersectional stigma and the psychosocial syndemic. Analyses will be conducted using generalised structural equation models using a cross-lagged panel model design. ETHICS AND DISSEMINATION: This protocol is approved as a single-IRB study (Advarra Institutional Review Board: Protocol 00068335). We will disseminate results via peer-reviewed academic journals, scientific conferences, a dedicated website, site community advisory boards and forums hosted at participating sites.

Proteomic Signature of HIV-Associated Subclinical Left Atrial Remodeling and Incident Heart Failure.

Background: People living with HIV (PLWH) are at higher risk of heart failure (HF) and preceding subclinical cardiac abnormalities, including left atrial dilation, compared to people without HIV (PWOH). Hypothesized mechanisms include premature aging linked to chronic immune activation. We leveraged plasma proteomics to identify potential novel contributors to HIV-associated differences in indexed left atrial volume (LAVi) among PLWH and PWOH and externally validated identified proteomic signatures with incident HF among a cohort of older PWOH. Methods: We performed proteomics (Olink Explore 3072) on plasma obtained concurrently with cardiac magnetic resonance imaging among PLWH and PWOH in the United States. Proteins were analyzed individually and as agnostically defined clusters. Cross-sectional associations with HIV and LAVi were estimated using multivariable regression with robust variance. Among an independent general population cohort, we estimated associations between identified signatures and LAVi using linear regression and incident HF using Cox regression. Results: Among 352 participants (age 55±6 years; 25% female), 61% were PLWH (88% on ART; 73% with undetectable HIV RNA) and mean LAVi was 29±9 mL/m 2 . Of 2594 analyzed proteins, 439 were associated with HIV serostatus, independent of demographics, hepatitis C virus infection, renal function, and substance use (FDR<0.05). We identified 73 of these proteins as candidate contributors to the independent association between positive HIV serostatus and higher LAVi, enriched in tumor necrosis factor (TNF) signaling and immune checkpoint proteins regulating T cell, B cell, and NK cell activation. We identified one protein cluster associated with LAVi and HIV regardless of HIV viral suppression status, which comprised 42 proteins enriched in TNF signaling, ephrin signaling, and extracellular matrix (ECM) organization. This protein cluster and 30 of 73 individual proteins were associated with incident HF among 2273 older PWOH (age 68±9 years; 52% female; 8.5±1.4 years of follow-up). Conclusion: Proteomic signatures that may contribute to HIV-associated LA remodeling were enriched in immune checkpoint proteins, cytokine signaling, and ECM organization. These signatures were also associated with incident HF among older PWOH, suggesting specific markers of chronic immune activation, systemic inflammation, and fibrosis may identify shared pathways in HIV and aging that contribute to risk of HF.

Association of urine biomarkers of kidney health with subclinical cardiovascular disease among men with and without HIV.

OBJECTIVE: The aim of this study was to determine whether urine biomarkers of kidney health are associated with subclinical cardiovascular disease among men with and without HIV. DESIGN: A cross-sectional study within the Multicenter AIDS Cohort Study (MACS) among 504 men with and without HIV infection who underwent cardiac computed tomography scans and had urine biomarkers measured within the preceding 2 years. METHODS: Our primary predictors were four urine biomarkers of endothelial (albuminuria), proximal tubule dysfunction (alpha-1-microglobulin [A1 M] and injury (kidney injury molecule-1 [KIM-1]) and tubulointerstitial fibrosis (pro-collagen-III N-terminal peptide [PIIINP]). These were evaluated for association with coronary artery calcium (CAC) prevalence, CAC extent, total plaque score, and total segment stenosis using multivariable regression. RESULTS: Of the 504 participants, 384 were men with HIV (MWH) and 120 were men without HIV. In models adjusted for sociodemographic factors, cardiovascular disease risk factors, eGFR, and HIV-related factors, each two-fold higher concentration of albuminuria was associated with a greater extent of CAC (1.35-fold higher, 95% confidence interval 1.11-1.65), and segment stenosis (1.08-fold greater, 95% confidence interval 1.01-1.16). Associations were similar between MWH and men without HIV in stratified analyses. The third quartile of A1 M showed an association with greater CAC extent, total plaque score, and total segment stenosis, compared with the lowest quartile. CONCLUSION: Worse endothelial and proximal tubule dysfunction, as reflected by higher urine albumin and A1 M, were associated with greater CAC extent and coronary artery stenosis.

Advance Care Planning Among Sexual Minority Men: Sociodemographic, Health Care, and Health Status Predictors.

Objectives: Advance care planning (ACP) specifies decision-making surrogates and preferences for serious illness or end-of-life medical care. ACP research has largely neglected sexual minority men (SMM), a population that experiences disparities in health care and health status. Methods: We examined formal and informal ACP among SMM ages 40+ in the Multicenter AIDS Cohort Study (N = 1,071). Results: For informal ACP (50%), younger SMM and men with past cardiovascular events had greater odds of planning; single men had lower odds of planning. For formal ACP (39%), SMM with greater socioeconomic status had greater odds of planning; SMM who were younger, of racial/ethnic minority identities, who were single or in a relationship without legal protections, and who lacked a primary care home had lower odds of planning. Discussion: Findings warrant further exploration of both informal and formal planning. More equitable, culturally-humble engagement of SMM may facilitate access, uptake, and person-centered planning.

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.

OBJECTIVES: 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 (≥40 years) men who have sex with men (MSM), and if this mediation/moderation differs by HIV serostatus. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Background and Objectives: 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. Research Design and Methods: 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. Results: 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. Discussion and Implications: 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.

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.

Plasma Glycomic Markers of Accelerated Biological Aging During Chronic HIV Infection.

People with HIV (PWH) experience an increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors that contribute to or are associated with this vulnerability remain uncertain. In the general population, alterations in the glycomes of circulating IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG glycomes of cross-sectional and longitudinal samples from 1,216 women and men, both living with virally suppressed HIV and those without HIV. Our glycan-based machine learning models indicate that living with chronic HIV significantly accelerates the accumulation of pro-aging-associated glycomic alterations. Consistently, PWH exhibit heightened expression of senescence-associated glycan-degrading enzymes compared to their controls. These glycomic alterations correlate with elevated markers of inflammatory aging and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit reduced anti-HIV IgG-mediated innate immune functions. These findings hold significant potential for the development of glycomic-based biomarkers and tools to identify and prevent premature aging and comorbidities in people living with chronic viral infections.

Psychosocial Syndemic Classes and Longitudinal Transition Patterns Among Sexual Minority men Living with or Without HIV in the Multicenter AIDS Cohort Study (MACS).

Mental health and substance use epidemics interact to create psychosocial syndemics, accelerating poor health outcomes. Using latent class and latent transition analyses, we identified psychosocial syndemic phenotypes and their longitudinal transition pathways among sexual minority men (SMM) in the Multicenter AIDS Cohort Study (MACS, n = 3,384, mean age 44, 29% non-Hispanic Black, 51% with HIV). Self-reported depressive symptoms and substance use indices (i.e., smoking, hazardous drinking, marijuana, stimulant, and popper use) at the index visit, 3-year and 6-year follow-up were used to model psychosocial syndemics. Four latent classes were identified: "poly-behavioral" (19.4%), "smoking and depression" (21.7%), "illicit drug use" (13.8%), and "no conditions" (45.1%). Across all classes, over 80% of SMM remained in that same class over the follow-ups. SMM who experienced certain psychosocial clusters (e.g., illicit drug use) were less likely to transition to a less complex class. These people could benefit from targeted public health intervention and greater access to treatment resources.

Syndemic trajectories of heavy drinking, smoking, and depressive symptoms are associated with mortality in women living with HIV in the United States from 1994 to 2017.

BACKGROUND: Heavy drinking, smoking, and depression are common among people with HIV. Little is known about the co-occurring, synergistic effect of having two or more of these conditions long-term -a sustained syndemic - on mortality among women with HIV (WWH). METHODS: Data from 3282 WWH of the Women's Interagency HIV Study from 1994 to 2017 were utilized. National Death Index review identified cause of death (n=616). Sustained syndemic phenotypes were based on membership in high-risk groups defined by group-based trajectory models of repeated self-reported alcohol use, smoking, and depressive symptoms and their co-occurrence. Cox proportional hazard models estimated associations of sustained syndemic phenotypes with all-cause, non-AIDS, and non-overdose mortality, adjusting for age, race/ethnicity, education, enrollment wave, illicit drug use, and time-varying HIV viral load and CD4+ T-cell count. RESULTS: WWH were 58% Black and 26% Hispanic, with a mean baseline age of 36.7 years. Syndemic phenotypes included zero (45%, n=1463), heavy drinking only (1%, n=35), smoking only (28%, n=928), depressive symptoms only (9%, n=282), and 2+ trajectories (17%, n=574). Compared to zero trajectories, having 2+ trajectories was associated with 3.93 times greater all-cause mortality risk (95% CI 3.07, 5.04) after controlling for confounders and each high-risk trajectory alone. These findings persisted in sensitivity analyses, removing AIDS- and overdose-related mortalities. CONCLUSIONS: Clustering of 2+ conditions of heavy drinking, smoking, and depression affected nearly one in five WWH and was associated with higher mortality than zero or one condition. Our findings underscore the need for coordinated screening and parsimonious treatment strategies for these co-occurring conditions.

Cumulative exposure to viremia: Methods for the implementation of standardized variables in longitudinal HIV studies.

Measures of viremic exposure over time, including HIV viral copy-years or durable viremic suppression, may be more relevant measures of viral load exposure for comorbid outcomes and mortality than single time point viral load measures. However, there are many subjective decisions that go into creating a cumulative variable such as HIV viral copy-years, including the appropriate anchoring point to begin accumulating exposure, the handling of viral load levels below an assay's lower limit of detection (LLD), the handling of gaps in the viral load trajectory, and when to apply the log10 transformation (before or after the accumulation calculation). Different decisions produce different values for HIV viral copy-years, and such differences could impact inferences in subsequent analyses of relationships with outcomes. In this paper, we develop several HIV viral copy-years variables that are standardized across:•Anchoring point•Handling of viral loads measured below the LLD and missing viral load measures•Application of the log10 transformation. These standardized variables may be consistently used in analyses of longitudinal cohort data. We also define a supplementary dichotomous HIV viral load exposure variable that may be used in tandem, or alternatively to, the HIV viral copy-years variables.

Individual-Level Psychosocial Resiliencies as Mediators of the Relationship Between Internalized Homophobia and Depressive Symptoms Among Middle-Aged and Older Men Living With and Without HIV.

Among sexual minority men (SMM), internalized homophobia (IH) has been consistently associated with increased depression symptoms. However, some SMM experiencing IH demonstrate resilience to buffer against depression symptoms. In this analysis, we used the Stress Process Model (SPM) as a conceptual framework to explore individual-level psychosocial resilience (ILPR) factors serving as a buffer of the IH-depression relationship. To utilize the SPM to explore whether four ILPR factors, including volunteerism, optimism, religiosity/spirituality, and global resiliency measure mediate the relationship between IH and depression symptoms among middle-aged and older SMM living with and without HIV. We used exploratory and confirmatory factor analysis to construct measurement models for the four ILPR factors. We examined whether the four ILPR factors mediated the IH-depression relationship. IH was significantly and positively associated with depression symptoms. There was a partial mediation of the IH-depression association by the four ILPR. Specifically, we found statistically significant indirect effects of optimism and the global resilience measure and supporting buffering effects of the IH-depression association. Although, the indirect effects religiosity/spirituality on the IH-depression relationship was significant, it did not support a buffering of effect. The indirect effects of volunteerism were not statistically significant. Our findings highlight the potential role of ILPR factors in the development of resilience against the negative effects of IH. Implications of these results for future research and practice are discussed.

The role of social support on cognitive function among midlife and older adult MSM.

OBJECTIVE: This study examines the association between social support and cognitive function among midlife and older MSM living with or without HIV. DESIGN: We analyzed longitudinal data from participants enrolled from October 2016 to March 2019 in the Patterns of Healthy Aging Study, a substudy of the Multicenter AIDS Cohort Study. METHODS: We conducted a cross-sectional analysis to estimate the association between social support and three measures of cognitive function [Trail Making Test (TMT) Part A, TMT Part B to A ratio, and Symbol Digit Modalities Tasks (SDMT)]. We also used linear mixed-effects models to estimate the association between baseline social support and cognitive function across four subsequent time points. We evaluated a multiplicative interaction term between baseline social support and time, in order to determine whether cognitive trajectories over time vary by baseline social support. RESULTS: Social support was associated with lower TMT Part A scores at baseline and over the subsequent 2 years, indicating better psychomotor ability. Social support was associated with higher SDMT scores at baseline and across 2 years, indicating better information processing. We observed no association between social support and TMT B to A ratio at baseline or across 2 years, indicating no effect on set-shifting ability. Longitudinal cognition outcome trajectories did not vary by the level of baseline social support. CONCLUSION: Social support and cognitive function were associated in this sample over a short time period. Further research should explore causal relationships over the lifespan.

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.

Menopausal Hormone Therapy and Subclinical Cardiovascular Disease in Women With and Without Human Immunodeficiency Virus.

BACKGROUND: Estrogen-based hormone therapy (HT) may have beneficial cardiovascular effects when initiated in early menopause. This has not been examined in women with human immunodeficiency virus (HIV), who have heightened immune activation and cardiovascular risks. METHODS: Among 609 postmenopausal women (1234 person-visits) in the Women's Interagency HIV Study, we examined the relationship of ever HT use (oral, patch, or vaginal) with subclinical atherosclerosis: carotid artery intima-media thickness (CIMT), distensibility, and plaque assessed via repeated B-mode ultrasound imaging (2004-2013). We also examined associations of HT with cross-sectional biomarkers of immune activation and D-dimer. Statistical models were adjusted for sociodemographic, behavioral, and cardiometabolic factors. RESULTS: Women (mean age, 51 years; 80% HIV positive) who ever used HT at baseline were older, and more likely to be non-Hispanic White and report higher income, than never-users. Women who ever used HT had 43% lower prevalence of plaque (prevalence ratio, 0.57 [95% confidence interval {CI}, .40-.80]; P < .01), 2.51 µm less progression of CIMT per year (95% CI, -4.60, to -.41; P = .02), and marginally lower incidence of plaque over approximately 7 years (risk ratio, 0.38 [95% CI, .14-1.03; P = .06), compared with never-users, adjusting for covariates; ever HT use was not associated with distensibility. These findings were similar for women with and without HIV. Ever HT use was associated with lower serum D-dimer, but not with biomarkers of immune activation after covariate adjustment. CONCLUSIONS: HT may confer a subclinical cardiovascular benefit in women with HIV. These results begin to fill a knowledge gap in menopausal care for women with HIV, in whom uptake of HT is very low.