Search

Partnership status among sexual minority men (SMM) is a potentially important yet underexplored predictor of cognitive functioning. Using data from the understanding patterns of healthy aging among men who have sex with men substudy of the Multicenter AIDS Cohort Study, we assessed the associations of partnership status and quality with cognitive performance in middle-aged and older SMM, adjusting for sociodemographic and clinical covariates. Partnership status was classified into four types: "only a primary partnership," "only a secondary partnership," "both a primary and secondary relationship," and "neither a primary nor secondary relationship." Partnership quality was assessed based on perceived support or strain from partners. Cognitive performance was evaluated using the z-scores on the Symbol Digit Modalities Test (SDMT), Trail Making Test Parts A (TMT-A) and B (TMT-B), and a composite Z-score that summed the SDMT, TMT-A, and TMT-B z-scores. Among 1067 participants (median age 60, 85.7% college educated), having a primary partner was associated with better cognitive performance (Z-score composite β ^ = 0.41 [95% CI 0.12-0.70]), TMT-A ( β ^ = 0.16 [95% CI 0.02-0.30]), and TMT-B ( β ^ = 0.19 [95% CI 0.06-0.33]). Support from secondary partners was also linked to better cognition. Additionally, there was a significant interaction between partnership and HIV status, indicating that SMM with HIV and both primary and secondary partners showed better cognitive outcomes than unpartnered SMM with HIV. These findings suggest that having a primary partner and receiving support from secondary partners may contribute to better cognitive health among middle-aged and older SMM, especially those with HIV., (© 2024. The Author(s).)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Interpersonal management of homophobic stigma (e.g., selectively constructing one's social network; confronting stigma) is an understudied area of resilience among sexual minority people. Among a sample of cisgender sexual minority men (SMM; N = 798) in midlife and older adulthood, we assessed the psychometric properties and characterized the sociodemographic differences of our newly developed, theory-informed homophobia management scale. Data come from the Healthy Aging substudy of the Multicenter AIDS Cohort Study, which is a prospective longitudinal study implemented to evaluate the natural trajectories of HIV risk and treatment among sexual minority men. Guided by the proactive coping processes model, the Healthy Aging team proposed eight items to measure homophobia management, which were included at four waves of survey data collection completed at semiannual study visits. Using factor analyses and linear regressions, we assessed our scale's construct validity, convergent validity, and internal consistency, and characterized scores by age, race/ethnicity, sexual orientation, and HIV status. Factor analyses yielded a six-item scale with adequate construct validity and acceptable internal consistency (Cronbach's alpha = .69). Our final scale exhibited convergent validity given its statistically significant inverse association with internalized homophobia and positive association with psychological connections to the gay community. Bivariate differences in homophobia management emerged by age, race/ethnicity, and sexual orientation but were not statistically significant in multivariable analyses. Our study provides a validated, unidimensional scale to assess homophobia management among SMM in midlife and older adulthood. We provide recommendations to improve the implementation of our scale in future surveillance., Competing Interests: Authors have no conflicts of interest to disclose.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: V. Stosor has grant support from Eli Lilly & Company paid to Northwestern University, has received an honorarium from Med Learning Group for educational lectures, and is a paid consultant for DiaSorin; none of these are directly related to the focus of this manuscript. M. Brennan-Ing receives research support from Gilead Sciences, and has worked as a consultant for Theratech; neither of these are directly related to the focus of this manuscript. Other authors have no conflicts to disclose.

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Jacobsen et al.)

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., Competing Interests: Declaration of Competing Interest Dr. Kizer reports stock ownership in Abbott, Bristol Myers Squibb, Johnson & Johnson, Medtronic, Merck, and Pfizer. Dr. Lahiri receives grant funding from Merck and serves on the Advisory Board for Theratechnologies, Inc. Dr. Adimora has received fees for consulting from Merck and Gilead. Merck and Gilead have provided her institution with funding for her research. Dr Palella has been a consultant or on the Speakers’ Bureau for ViiV, Gilead, Janssen and Merck. None of the other authors had any financial or other conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Potential conflicts of interest. P. C. T. has received research funding from Merck (paid to institution) and Gilead to conduct sponsor-initiated clinical trials, unrelated to the current manuscript; grants or contracts (paid to institution), outside the submitted work, from Lilly; and royalties paid to self from UpToDate. A. A. A. has received consulting fees from Merck and Gilead; Merck and Gilead have also provided her institution with funding for her research. H. N. H. reports grants or contracts from the NIA, NIH (R01-AG059690 and R01-AG058691) and the Institute of Environmental Health, NIH (R01-ES031590), all outside the submitted work; payment or honoraria for a keynote lecture on menopause from the American Society of Reproductive Medicine; and data and safety monitoring board (DSMB) Chair, Flushing Reduction Associated With Nitrates (R01-AG050588) and DSMB for NIA-funded project (concluded). E. A. J. reports grants or contracts from the NIH outside the submitted work; royalties or licenses from UpToDate; consulting fees from the American College of Cardiology and McKesson; payment for expert testimony from DeBalse, Brown, Everly, LLP; and participation on a DSMB or advisory board for the NIH. K. A. reports additional grants from the NIH (paid to institution), outside the submitted work, and support for attending meetings and/or travel from the NIH (paid to institution). M. T. Y. reports support for the present manuscript from National Institute of Allergy and Infectious Diseases (K24 AI155230). M. L. A. reports grants or contracts from NIH MWCCS, outside the submitted work. A. S. reports grant funding from Gilead Sciences, outside the submitted work, and consulting fees from Gilead Sciences. I. O. reports grants or contracts from Merck, outside the submitted work. D. B. H. reports grants or contracts from the NIH (paid to institution), outside of the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Insights into combination HIV prevention (CHP) strategies to reduce HIV incidence among midlife and older adult men who have sex with men (MSM) are limited. The current study is a secondary data analysis evaluating CHP in a sample of sexually active midlife and older adult MSM ( N  = 566) from the Multicenter AIDS Cohort Study Healthy Aging Substudy. Stratified by HIV serostatus, we used latent class analyses to identify CHP classes based on self-reported sociobehavioral and biobehavioral prevention strategies that participants and their male partners used in the prior 6 months. We identified three CHP classes among men living without HIV (MLWOH), including the following: high CHP overall (43.0%), high anal sex abstention (15.0%), and low prevention overall (42.0%). Among men living with HIV (MLWH), we identified four CHP classes, including the following: high CHP overall (20.9%), high CHP/low condom use (27.1%), high condom reliance (22.3%), and low prevention overall (29.7%). There were small differences by sociodemographic characteristics and sexual behavior practices between the classes; however, poppers use was often linked to being in high CHP groups. Our findings support that CHP is not one-size-fits-all for midlife and older adult MSM. There remains a need to scale up clinical providers' sexual health communication practices to assist midlife and older MSM incorporate prevention strategies, particularly biobehavioral prevention strategies that align with their patients' lived experiences.

Background: Infection with human immunodeficiency virus (HIV) is associated with higher risk for myocardial disease despite modern combination antiretroviral therapy (cART). Factors contributing to this excess risk, however, remain poorly characterized. We aimed to assess cross-sectional relationships between elevations of left atrial volume index (LAVI) and myocardial extracellular volume (ECV) fraction that have been reported in persons living with HIV and levels of circulating biomarkers of inflammation, fibrosis, and myocyte stretch among persons living with and without HIV (PLWH, PLWOH)., Methods: Participants from three cohorts of PLWH and PLWOH underwent cardiovascular magnetic resonance imaging for measurement of LAVI and ECV. Levels of circulating proteins (IL-6, sCD14, galectin-3, NT-proBNP, GDF-15, TIMP-2, MMP-2, and hsTnI) were measured using immunoassays. Associations were assessed using logistic and linear regression, adjusting for demographics, substance use, and clinical characteristics., Results: Among 381 participants with and without HIV, median age (IQR) was 55.1 (51.2, 58.4) years, 28% were female, 69% were Black, and 46% were current smokers. Sixty-two percent were PLWH (n = 235), of whom 88% were receiving cART and 72% were virally suppressed. PLWH had higher levels of sCD14 (p = < 0.001), GDF-15 (p = < 0.001), and NT-proBNP (p = 0.03) compared to PLWOH, while levels of other biomarkers did not differ by HIV serostatus, including IL-6 (p = 0.84). Among PLWH, higher sCD14, GDF-15, and NT-proBNP were also associated with lower CD4 + cell count, and higher NT-proBNP was associated with detectable HIV viral load. NT-proBNP was associated with elevated LAVI (OR: 1.79 [95% CI: 1.31, 2.44]; p < 0.001) with no evidence of effect measure modification by HIV serostatus. Other associations between HIV-associated biomarkers and LAVI or ECV were small or imprecise., Conclusions: Our findings suggest that elevated levels of sCD14, GDF-15, and NT-proBNP among PLWH compared to PLWOH observed in the current cART era may only minimally reflect HIV-associated elevations in LAVI and ECV. Future studies of excess risk of myocardial disease among contemporary cohorts of PLWH should investigate mechanisms other than those connoted by the studied biomarkers., (© 2022. The Author(s).)

Objective: To use accelerometers to quantify differences in physical activity (PA) by HIV serostatus and HIV viral load (VL) in the Multicenter AIDS Cohort Study (MACS)., Methods: MACS participants living with (PLWH, n = 631) and without (PWOH, n = 578) HIV wore an ambulatory electrocardiogram monitor containing an accelerometer for 1-14 days. PA was summarized as cumulative mean absolute deviation (MAD) during the 10 most active consecutive hours (M10), cumulative MAD during the six least active consecutive hours (L6), and daily time recumbent (DTR). PA summaries were compared by HIV serostatus and by detectability of VL (>20 vs. ≤20 copies/ml) using linear mixed models adjusted for sociodemographics, weight, height, substance use, physical function, and clinical factors., Results: In sociodemographic-adjusted models, PLWH with a detectable VL had higher L6 (β = 0.58 mg, P = 0.027) and spent more time recumbent (β = 53 min/day, P = 0.003) than PWOH. PLWH had lower M10 than PWOH (undetectable VL β = -1.62 mg, P = 0.027; detectable VL β = -1.93 mg, P = 0.12). A joint test indicated differences in average PA measurements by HIV serostatus and VL (P = 0.001). However, differences by HIV serostatus in M10 and DTR were attenuated and no longer significant after adjustment for renal function, serum lipids, and depressive symptoms., Conclusions: Physical activity measures differed significantly by HIV serostatus and VL. Higher L6 among PLWH with detectable VL may indicate reduced amount or quality of sleep compared to PLWH without detectable VL and PWOH. Lower M10 among PLWH indicates lower amounts of physical activity compared to PWOH., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: People living with HIV (HIV+) are surviving longer due to effective antiretroviral therapy. Cardiovascular disease is a leading cause of non-AIDS related clinical events. We determined HIV-related factors associated with coronary artery stenosis progression., Methods: We performed serial coronary CT angiography among HIV+ and HIV-uninfected (HIV-) men in the Multicenter AIDS Cohort Study. The median inter-scan interval was 4.5 years. Stenosis was graded as 0, 1-29, 30-49, 50-69 or ≥70%. Progression was defined as an increase ≥2 categories. Suppressed HIV infection was consistent viral loads <50 copies/mL allowing 1 "blip" <500 copies/mL, otherwise considered viremic. Multivariable Poisson regression analysis assessed adjusted associations between HIV serostatus and viremia with coronary stenosis progression., Results: The sample included 310 HIV+ (31% viremic) and 234 HIV- men. The median age was 53 years, 30% Black and 23% current smokers. Viremic men were 2.3 times more likely to develop coronary stenosis progression than HIV- men (adjusted RR 2.30; 95% CI, 1.32-4.00, p = 0.003), with no difference in progression between HIV+ suppressed and HIV- men (RR 1.10; 95% CI, 0.70-1.74, p = 0.67). There was a progressive increase in adjusted relative risk with greater viremia (p = 0.03). Men with >1 viral load >500 copies/ml demonstrated greatest stenosis progression (RR 3.01; 95% CI, 1.53-4.92, p = 0.001 compared with HIV- men). Suppressed HIV+ men with suboptimal antiretroviral adherence had greater stenosis progression (RR 1.91; 95% CI 1.12-3.24, p = 0.02) than HIV + suppressed men with optimal adherence., Conclusions: Coronary artery stenosis progression was associated with suboptimal HIV RNA suppression and antiretroviral therapy adherence. Effective ongoing HIV virologic suppression and antiretroviral therapy adherence may mitigate risk for coronary disease events among people living with HIV., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives. To determine whether intersectional stigma is longitudinally associated with biopsychosocial outcomes. Methods. We measured experienced intersectional stigma (EIS; ≥ 2 identity-related attributions) among sexual minority men (SMM) in the United States participating in the Multicenter AIDS Cohort Study. We assessed longitudinal associations between EIS (2008‒2009) and concurrent and future hypertension, diabetes, dyslipidemia, antiretroviral therapy adherence, HIV viremia, health care underutilization, and depression symptoms (2008‒2019). We conducted causal mediation to assess the contribution of intersectional stigma to the relationship between self-identified Black race and persistently uncontrolled outcomes. Results. The mean age (n = 1806) was 51.8 years (range = 22-84 years). Of participants, 23.1% self-identified as Black; 48.3% were living with HIV. Participants reporting EIS (30.8%) had higher odds of hypertension, dyslipidemia, diabetes, depression symptoms, health care underutilization, and suboptimal antiretroviral therapy adherence compared with participants who did not report EIS. EIS mediated the relationship between self-identified Black race and uncontrolled outcomes. Conclusions. Our findings demonstrate that EIS is a durable driver of biopsychosocial health outcomes over the life course. Public Health Implications. There is a critical need for interventions to reduce intersectional stigma, help SMM cope with intersectional stigma, and enact policies protecting minoritized people from discriminatory acts. ( Am J Public Health . 2022;112(S4):S452-S462. https://doi.org/10.2105/AJPH.2022.306735).

Background The prevalence and extent of subclinical large vessel vasculopathy is not well defined among people living with HIV. We aimed to evaluate associations between aortic root and ascending aortic sizes measured by 2-dimensional transthoracic echocardiography and HIV serostatus, and to identify risk factors for larger aortic sizes among men with HIV, including levels of circulating inflammatory markers. Methods and Results Using clinical and echocardiographic data from the MACS (Multicenter AIDS Cohort Study), adjusted multivariable linear and logistic regression was performed. Four segments of the proximal aorta were measured: aortic annulus, aortic root at the sinuses of Valsalva, sinotubular junction, and ascending aorta. HIV infection was associated with significantly larger aortic root (0.03 cm [95% CI, 0.002-0.06 cm]) and ascending aorta (0.04 cm [95% CI, 0.01-0.06 cm]) diameters. Higher standardized nadir CD4 (cluster of differentiation 4) T-cell count was significantly associated with smaller aortic root (-0.03 cm [95% CI, -0.05 to -0.01 cm]), sinotubular junction (-0.03 cm [95% CI, -0.05 to -0.01 cm]), and ascending aorta (-0.03 cm [95% CI, -0.05 to -0.004 cm]) diameters. Higher levels of standardized TNF-α (tumor necrosis factor-α) were associated with larger diameters of the aortic annulus (0.02 cm [95% CI, 0.003-0.04 cm]) and sinotubular junction (0.02 cm [95% CI, 0.002-0.04 cm]). There were no other cardiovascular or HIV disease severity-related risk factors associated with the aortic dimensions. Conclusions HIV infection is an independent risk factor for greater ascending aortic sizes. Lower nadir CD4 T-cell count and higher TNF-α levels are associated with larger aortic sizes in men with HIV. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00046280.

Background: With the graying of sexual and gender minority communities and the growing number of people aged ≥50 years living with HIV, it is increasingly important to understand resilience in the context of the psychosocial aspects of aging and aging well., Objective: This paper aims to describe the methods and sample for the Understanding Patterns of Healthy Aging Among Men Who Have Sex With Men study., Methods: This observational cohort study was conducted within the Multisite AIDS Cohort Study (MACS) and was designed to explore resiliencies to explain patterns of health and illness among middle-aged and older sexual minority men. To be eligible, a participant had to be an active participant in the MACS, be at least 40 years of age as of April 1, 2016, and report any sex with another man since enrollment in the MACS., Results: Eligible participants (N=1318) completed six biannual surveys between April 2016 and April 2019. The mean age of the sample was 59.6 years (range 40-91 years). The sample was mostly White, educated, gay-identified, and included both HIV-positive (656/1318, 49.77%) and HIV-negative (662/1318, 50.23%) men., Conclusions: Understanding resiliencies in aging is a critical springboard for the development of more holistic public health theories and interventions that support healthy aging among older sexual minority men., International Registered Report Identifier (irrid): RR1-10.2196/25750., (©James E Egan, Sabina A Haberlen, Steven Meanley, Deanna Ware, Andre L Brown, Daniel Siconolfi, Mark Brennan-Ing, Ron Stall, Michael W Plankey, M Reuel Friedman. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 23.09.2021.)

Background and Objectives: Older people have an increased risk of developing frailty, an age-related clinical syndrome associated with worse health outcomes. This study examined the effect of self-perception of aging (ie, age discrepancy-individuals feel younger/older than their chronological age and aging satisfaction) on frailty transitions., Research Design and Methods: We use longitudinal data from 549 HIV-/499 HIV+ sexual minority men aged 50 years or older enrolled in the Multicenter AIDS Cohort Study. To test the association of self-perception of aging on transitions between states of frailty (nonfrail/frail), defined using Fried Frailty Phenotype, a multinomial modeling was used., Results: With remaining nonfrail as the referent group, participants reporting low aging satisfaction (vs moderate aging satisfaction) had increased odds of transitioning from nonfrail to frail (odds ratio [OR]: 2.72; 95% confidence interval [CI]: 1.56-4.74), frail to nonfrail (OR: 3.40; 95% CI: 1.62-7.12), or remaining frail (frail to frail; OR: 6.64; 95% CI: 3.88-11.38). Participants reporting older subjective age (vs no age discrepancy) had increased odds of transitioning from nonfrail to frail (OR: 2.50; 95% CI: 1.11-5.64), frail to nonfrail (OR: 4.47; 95% CI: 1.85-10.81), or remaining frail (frail to frail; OR: 5.68; 95% CI: 3.06-10.56). High aging satisfaction and younger subjective age were not statistically associated with frailty transitions., Discussion and Implications: Our findings show that negative self-perception of aging (ie, older subjective age and low aging satisfaction) is associated with frailty transitions (nonfrail to frail, frail to nonfrail, and frail to frail) when compared to remaining nonfrail., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: Sex hormone-binding globulin (SHBG) is a glycoprotein that regulates sex hormone bioavailability and increases with age in the general population. SHBG concentrations are higher in people with HIV, a population in whom accelerated aging has been hypothesized. It is unclear whether longitudinal changes in SHBG increase over time and differ by HIV serostatus., Methods: In a longitudinal study, SHBG was measured in 182 men with HIV (MWH) and 267 men without HIV (seronegative) from the Multicenter AIDS Cohort Study and matched for age, race, site, and time, with ≥2 SHBG serum samples over the 10 years after HAART initiation. Multivariable linear mixed-effects regression models were used to evaluate whether log-transformed SHBG [ln(SHBG)] and its rate of change differed by HIV serostatus., Results: At baseline, the mean age in MWH was similar to that in HIV-seronegative men (51 ± 5 vs 49 ± 6 years). However, SHBG mean values were higher in MWH compared with those in HIV-seronegative men (65.6 ± 48.8 vs. 45.4 ± 22 nmol/L, P < 0.001). In a fully adjusted model, SHBG increased over time and at a faster rate in MWH compared with that in HIV-seronegative men: [2.0%/year (95% CI: 1.4 to 2.7) vs 1.3%/year (95% CI: 0.8 to 1.8), respectively, P = 0.038]. Among MWH, higher SHBG concentrations were significantly associated with lower CD4+ T-cell count [β= -0.02 (95% CI: -0.03 to -0.0002), P < 0.05], fewer cumulative years on zidovudine [β = -0.027 (95% CI: -0.045 to -0.009), P < 0.001], and greater cumulative years on nonnucleoside reverse transcriptase inhibitors drugs [β = 0.022 (95% CI: 0.0006 to 0.04), P < 0.05]., Conclusions: Aging-related increases in SHBG were faster in MWH compared with those in HIV-seronegative men and were related to poorer immunologic status and antiretroviral medication exposure. The mechanisms and consequences of these findings require further investigation., Competing Interests: T.T.B. has served as a consultant to ViiV Healthcare, Janssen, Merck, Gilead Sciences, and Theratechnologies. J.E.L. has served as a consultant to ViiV and Merck and receives research support from Gilead Sciences and CytoDyn. J.C. Price has served as a consultant to Theratechnologies and receives research support from Gilead Sciences and Merck. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Atrial fibrillation (AF) leads to increased risk for stroke. Human immunodeficiency virus (HIV) is associated with cardiovascular disease (CVD), although it is unclear if HIV is associated with AF. The purpose of this study was to evaluate the association between HIV serostatus and the prevalence of AF in the Multicenter AIDS Cohort Study.A cross sectional study was conducted among 1674 HIV-infected (HIV+) and uninfected (HIV-) men who completed resting 12-lead electrocardiograms, and/or ambulatory electrocardiogram monitoring. Multivariable logistic regression was used to evaluate the association between AF, defined as the presence of either AF or atrial flutter, and HIV+ serostatus. Associations were adjusted for demographic variables, and then also for CVD risk factors.HIV+ men were younger than HIV- men (median 55.5 vs 61.7 years, P < .001) and were more frequently African-American (30.5% vs 17.8%, P < .001). Most HIV+ men (81%) had undetectable viral load. The age and race adjusted prevalence of AF was 3.0% in HIV+ and 3.3% in HIV- men. There was only 1 case of AF among African-American men. There were no associations between AF and HIV serostatus after adjusting for demographic factors (odds ratio 0.76; 95% CI 0.37 to -1.58; P = .47) or after further adjustment for CVD risk factors (odds ratio 0.84; 95% CI 0.39 to -1.81; P = .66).We found no association between HIV and AF in this cohort in which viral replication among the HIV+ men is generally suppressed. The overall prevalence of AF was low and was rare in African-American men., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: The extent to which human immunodeficiency viral (HIV) infection is independently associated with myocardial disease in the era of combination antiretroviral therapy (cART) remains understudied. We assessed differences in cardiovascular magnetic resonance imaging (CMR) metrics among people living with HIV (PLWH) and without HIV (PWOH)., Methods and Results: Among 436 participants (aged 54.7 ± 6.0 years, 29% women) from three cohorts, we acquired CMR cines, late gadolinium enhancement (LGE), and T1 mapping. Multivariable linear regressions were used to evaluate associations between HIV serostatus and CMR metrics. Baseline characteristics were similar by HIV serostatus; 63% were PLWH of whom 88% received cART and 73% were virally suppressed. Median left ventricular ejection fraction was normal and similar by HIV serostatus (73%, PWOH vs. 72%, PLWH, P = 0.43) as were right ventricular function, biventricular volumes, and masses. LGE prevalence was similar (32%, PWOH vs. 36%, PLWH, P = 0.46) with low scar extents (4.1, PWOH vs. 4.9 g, PLWH, P = 0.51) and few ischaemic scars (3%, PWOH vs. 4%, PLWH, P = 0.70). Extracellular volume fraction (ECV) was higher among PLWH (29.2 ± 4.1% vs. 28.3 ± 3.7%, P = 0.04) as was indexed maximum left atrial (LA) volume (LAVI, 29.7 ± 10.3 vs. 27.8 ± 8.7 mL/m2, P = 0.05). After multivariate adjustment, ECV was 0.84% higher among PLWH (P = 0.05) and LAVI was 2.45 mL/m2 larger (P = 0.01). HIV seropositivity and higher ECV contributed to higher LAVI (P < 0.02). There were no associations between HIV disease severity and CMR metrics among PLWH., Conclusion: HIV seropositivity was independently associated with greater diffuse non-ischaemic fibrosis and larger LA volume but no other differences in CMR metrics., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Objectives: Testosterone usage (T-use) may alter risk factors for sudden cardiac death in men living with HIV (MLWH). Electrocardiographic QT interval prolongation, which could potentiate ventricular arrhythmias, has previously been associated with HIV infection and, separately, with low testosterone levels. We investigated whether T-use shortens the QT interval duration in MLWH and HIV-uninfected men., Methods: We utilized data from the Multicenter AIDS Cohort Study, a prospective, longitudinal study of HIV infection among men who have sex with men. Multivariable linear regression analyses were used to evaluate associations between T-use and corrected QT interval (QTc) duration., Results: Testosterone usage was more common in MLWH compared with HIV-uninfected men (19% vs. 9%). In a multivariable regression analysis, T-use was associated with a 5.7 ms shorter QT interval [95% confidence interval (CI): -9.5 to -1.9; P = 0.003). Furthermore, stronger associations were observed for prolonged duration of T-use and recent timing of T-use., Conclusions: This study is the first known analysis of T-use and QTc interval in MLWH. Overall, our data demonstrate that recent T-use is associated with a shorter QTc interval. Increased T-use duration above a threshold of ≥ 50% of visits in the preceding 5 years was associated with a shorter QTc interval while lesser T-use duration was not., (© 2020 British HIV Association.)

Background We aimed to investigate whether there are differences in cardiac structure and systolic and diastolic function evaluated by 2-dimensional echocardiography among men living with versus without HIV in the era of combination antiretroviral therapy. Methods and Results We performed a cross-sectional analysis of 1195 men from MACS (Multicenter AIDS Cohort Study) who completed a transthoracic echocardiogram examination between 2017 and 2019. Associations between HIV serostatus and echocardiographic indices were assessed by multivariable regression analyses, adjusting for demographics and cardiovascular risk factors. Among men who are HIV+, associations between HIV disease severity markers and echocardiographic parameters were also investigated. Average age was 57.1±11.9 years; 29% of the participants were Black, and 55% were HIV+. Most men who were HIV+ (77%) were virally suppressed; 92% received combination antiretroviral therapy. Prevalent left ventricular (LV) systolic dysfunction (ejection fraction <50%) was low and HIV serostatus was not associated with left ventricular ejection fraction. Multivariable adjustment models showed that men who were HIV+ versus those who were HIV- had greater LV mass index and larger left atrial diameter and right ventricular (RV) end-diastolic area; lower RV function; and higher prevalence of diastolic dysfunction. Higher current CD4+ T cell count ≥400 cell/mm 3 versus <400 was associated with smaller LV diastolic volume and RV area. Virally suppressed men who were HIV+ versus those who were HIV- had higher indexed LV mass and left atrial areas and greater diastolic dysfunction. Conclusions HIV seropositivity was independently associated with greater LV mass index, left atrial and RV sizes, lower RV function and diastolic abnormalities, but not left ventricular ejection fraction, which may herald a future predisposition to heart failure with preserved ejection fraction among men living with HIV.

Rationale: Loneliness is associated with negative health outcomes, such as cardiovascular disease, cognitive impairment, dementia, physical functional decline, depression, and increased mortality risk, among HIV- positive and HIV-negative older men who have sex with men (MSM). Given these negative health outcomes, it is imperative to identify factors that minimize loneliness in these vulnerable groups., Objective: We sought to examine whether social-environmental resiliencies-defined as an individual's level of support, social bonding, and psychological sense of community among gay men-buffer against symptoms of loneliness., Method: We analyzed longitudinal data from 1,255 older MSM with and without HIV infection, all of whom were enrolled in the Multicenter AIDS Cohort Study (MACS). Using longitudinal latent class analysis (LLCA), we identified three underlying classes (Social Connectors, Non-community Connectors, and Social Isolates) in the social environment of the sample. We assessed the prevalence of loneliness by these latent classes. By lagging social environmental factors over time, we were able to examine the temporal relationships between latent classes and subsequent loneliness., Results: Consistent with our hypothesis, multivariate associations revealed that compared to Social Connectors with high levels of social support and social bonding and a strong perceived sense of community among gay men, Social Isolates (Prevalence Ratio (PR): 1.42; 95% CI: 1.08-1.88; p = 0.0120) and Non-community Connectors (PR: 1.34; 95% CI: 1.03-1.75; p = 0.0322) were more likely to experience loneliness after adjustment for covariates and baseline loneliness. There were no differences by HIV status., Conclusions: These longitudinal data allowed us to make causal inferences related to the social environmental resiliencies lowering the odds of loneliness among HIV-positive and HIV-negative older MSM. Developing individual- and community-level tailored interventions for these populations by leveraging social environmental resiliencies is key to reducing loneliness and promoting health., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The present study was designed to identify social support classes across time among midlife (40-64 years) and older (65+ years) gay, bisexual, and other men who have sex with men (MSM), and whether social support protects against depressive symptoms in this population. This study applied longitudinal latent class analysis across five visits on 1,329 individuals age 40 or older at baseline using data from the Multicenter AIDS Cohort Study (MACS) Healthy Aging substudy collected from April 2016 to October 2018. We identified four classes of social support across time: Partner-centered , that is, high levels of support from one's primary partner(s) and moderate support from friends and family; Friend-centered , that is, high levels of support from friends and chosen family; Low , that is, low levels of support from all sources; and Robust , that is, high levels of support from all sources. We found differences in class membership by age, race/ethnicity, employment status, sexual identity, education, relationship status, and HIV status. Finally, compared to MSM in the low support class, men in the other classes had lower odds of depressive symptoms at the final visit. The most common type of social support was partner-centered, while the least common type was robust. These findings suggest that the presence of any social support, regardless of the source, protects against depressive symptoms., Competing Interests: Disclosure. The authors have no relevant financial interest or affiliations with any commercial interests related to the subjects discussed within this article.

Background and Objectives: Conversion therapies to minimize same-sex attractions are classified as a dangerous practice by numerous scientific institutions in the United States. These practices may contribute to poor long-term psychosocial health, thereby interrupting processes of healthy aging. Few studies have examined psychosocial differences between persons with and without prior experiences of conversion therapy. We assessed associations between prior conversion therapy experiences and psychosocial health among midlife and older men who have sex with men (MSM; age 40+ years)., Research Design and Methods: Participants included a multicity sample of MSM (N = 1,156) enrolled in the Multicenter AIDS Cohort Study who completed health surveys (2016-2019) as part of their biannual study visits. Using multivariable regressions, we investigated the associations of prior conversion therapy with current depressive symptoms, internalized homophobia, post-traumatic stress, and cumulative psychosocial conditions. Using a trait-level measure (e.g., life purpose and perseverance), we tested whether resilience moderated these associations., Results: The full sample was predominantly non-Hispanic white with a mean age of 62.6 years. Fifteen percent of men (n = 171/1,156) reported prior conversion therapy. In multivariable models, men exposed to conversion therapy were more likely to have depressive symptoms and above-average internalized homophobia. Men exposed to conversion therapy had 2-2.5 times the odds of reporting 1 and ≥2 psychosocial conditions, respectively, compared with those who reported 0 conditions. Resilience did not moderate these associations., Discussion and Implications: Conversion therapies are nonaffirming social stressors for MSM and may compromise critical psychosocial aspects of healthy aging among MSM., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Conversion therapies are practices that attempt to change an individuals' same-sex attractions through psychotherapeutic and aversive therapeutic techniques. Conversion therapies were developed based on homophobic beliefs that same-sex attractions are a mental illness. We sought to describe the prevalence and characteristics of conversion therapy experienced among middle-aged and older men who have sex with men in the United States. Given associations of homophobic stigma and HIV risk, we hypothesized that HIV-positive men would report higher odds of conversion therapy compared to HIV-negative men. We analyzed data from 1,237 middle-aged and older MSM enrolled in the Multicenter AIDS Cohort Study. Among participants, 17.7% reported lifetime conversion therapy, of which the average start of therapy age was 22.67 ( sd = 10.56) years, 25.8% reported therapy durations of 6+ months, 37.7% reported session frequencies 1+ session per week, and 35.9% indicated that undergoing therapy was either a little or not at all their decision. We observed no statistically significant association between reporting lifetime conversion therapy and HIV status. Future efforts should continue to assess the magnitude of harm conversion therapies impose on MSM's health across the life course as well as test potential, indirect associations that may link these practices to HIV.

Background: The total QT interval comprises both ventricular depolarization and repolarization currents. Understanding how HIV serostatus and other risk factors influence specific QT interval subcomponents could improve our mechanistic understanding of arrhythmias., Methods: Twelve-lead electrocardiograms (ECGs) were acquired in 774 HIV-infected (HIV+) and 652 HIV-uninfected (HIV-) men from the Multicenter AIDS Cohort Study. Individual QT subcomponent intervals were analyzed: R-onset to R-peak, R-peak to R-end, JT segment, T-onset to T-peak, and T-peak to T-end. Using multivariable linear regressions, we investigated associations between HIV serostatus and covariates, including serum concentrations of inflammatory biomarkers such as interleukin-6 (IL-6), and each QT subcomponent., Results: After adjustment for demographics and risk factors, HIV+ versus HIV- men differed only in repolarization phase durations with longer T-onset to T-peak by 2.3 ms (95% CI 0-4.5, p < .05) and T-peak to T-end by 1.6 ms (95% CI 0.3-2.9, p < .05). Adjusting for inflammation attenuated the strength and significance of the relationship between HIV serostatus and repolarization. The highest tertile of IL-6 was associated with a 7.3 ms (95% CI 3.2-11.5, p < .01) longer T-onset to T-peak. Age, race, body mass index, alcohol use, and left ventricular hypertrophy were each associated with up to 2.2-12.5 ms longer T-wave subcomponents., Conclusions: HIV seropositivity, in combination with additional risk factors including increased systemic inflammation, is associated with longer T-wave subcomponents. These findings could suggest mechanisms by which the ventricular repolarization phase is lengthened and thereby contribute to increased arrhythmic risk in men living with HIV., (© 2019 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals, Inc.)

Importance: Lipid metabolism disruption and excess risk of cardiovascular disease (CVD) have been observed in HIV-infected individuals, but the associations among HIV infection, plasma lipidome, and CVD risk have not been well understood., Objective: To evaluate plasma lipidomic profiles and their associations with carotid artery atherosclerosis in individuals with HIV and individuals without HIV., Design, Setting, and Participants: Prospective analysis in the Women's Interagency HIV Study and Multicenter AIDS Cohort Study during a 7-year follow-up (from 2004-2006 to 2011-2013) at multicenter HIV cohorts in the United States. The study included 737 participants aged 35 to 55 years (520 with HIV and 217 without HIV) without CVD or carotid artery plaque at baseline. Data were analyzed between April 2017 and July 2019., Exposures: Two hundred eleven plasma lipid species., Main Outcomes and Measures: Poisson regression was used to examine the associations of baseline lipid species with risk of plaque measured by repeated B-mode carotid artery ultrasonography imaging., Results: Of the 737 included participants, 398 (54%) were women, 351 (48%) were African American (non-Hispanic), 156 of 737 (21%) were nonwhite Hispanic, and the mean (SD) age was 45 (6) years. After adjusting for demographic and behavioral factors, we identified 12 lipid species, representing independent signals for 10 lipid classes, associated with risk of plaque. Nine lipid species remained significant after further adjusting for conventional CVD risk factors, although many of them showed moderate to high association with conventional blood lipids (eg, total and low-density lipoprotein cholesterols and triglycerides). Cholesteryl ester (16:1) (risk ratio [RR] per standard deviation, 1.28; 95% CI, 1.08-1.52), ceramide (16:0) (RR, 1.29; 95% CI, 1.02-1.63), lysophosphatidylcholine (20:4) (RR, 1.28; 95% CI, 1.05-1.58), lysophosphatidylethanolamine (16:0) (RR, 1.28; 95% CI, 1.05-1.57), phosphatidylethanolamine (38:6) (RR, 1.33; 95% CI, 1.08-1.64), phosphatidylethanolamine-plasmalogen (36:2) (RR, 1.25; 95% CI, 1.04-1.52), phosphatidylserine-plasmalogen (36:3) (RR, 1.19; 95% CI, 1.00-1.43), and triacylglycerol (54:6) (RR, 1.26; 95% CI, 1.04-1.54) were associated with increased risk of plaque, while phosphatidylcholine (36:4) (RR, 0.65; 95% CI, 0.54-0.77) was associated with decreased risk of plaque. Most of these plaque-increased lipid species showed higher levels in individuals with HIV, particularly among individuals with HIV using antiretroviral therapy compared with individuals without HIV. Network analysis identified 9 lipid modules, and 2 modules composed of triacylglycerols and phosphatidylcholines with long and unsaturated acyl chains, respectively, showed the strongest associations with increased risk of plaque., Conclusions and Relevance: This study identified multiple plasma lipid species associated with carotid artery atherosclerosis, and alterations in these lipid species might be associated with HIV infection and antiretroviral therapy. Our data suggest unfavorable associations of long-chain and unsaturated triacylglycerols and phosphatidylcholines with carotid artery plaque formation.

Background: Subfertility among couples affected by HIV has an impact on the well-being of couples who desire to have children and may prolong HIV exposure. Subfertility in the antiretroviral therapy era and its determinants have not yet been well characterized., Objective: The objective of the study was to investigate the burden and determinants of subfertility among HIV-affected couples seeking safer conception services in South Africa., Study Design: Nonpregnant women and male partners in HIV seroconcordant or HIV discordant relationships desiring a child were enrolled in the Sakh'umndeni safer conception cohort at Witkoppen Clinic in Johannesburg between July 2013 and April 2017. Clients were followed up prospectively through pregnancy (if they conceived) or until 6 months of attempted conception, after which they were referred for infertility services. Subfertility was defined as not having conceived within 6 months of attempted conception. Robust Poisson regression was used to assess the association between baseline characteristics and subfertility outcomes; inverse probability weighting was used to account for missing data from women lost to safer conception care before 6 months of attempted conception., Results: Among 334 couples enrolled, 65% experienced subfertility (inverse probability weighting weighted, 95% confidence interval, 0.59-0.73), of which 33% were primary subfertility and 67% secondary subfertility. Compared with HIV-negative women, HIV-positive women not on antiretroviral therapy had a 2-fold increased risk of subfertility (weighted and adjusted risk ratio, 2.00; 95% confidence interval, 1.19-3.34). Infertility risk was attenuated in women on antiretroviral therapy but remained elevated, even after ≥2 years on antiretroviral therapy (weighted and adjusted risk ratio, 1.63; 95% confidence interval, 0.98-2.69). Other factors associated with subfertility were female age (weighted and adjusted risk ratio, 1.03, 95% confidence interval, 1.01-1.05 per year), male HIV-positive status (weighted and adjusted risk ratio, 1.31; 95% confidence interval, 1.02-1.68), male smoking (weighted and adjusted risk ratio, 1.29; 95% confidence interval, 1.05-1.60), and trying to conceive for ≥1 year (weighted and adjusted risk ratio, 1.38; 95% confidence interval, 1.13-1.68)., Conclusion: Two in 3 HIV-affected couples experienced subfertility. HIV-positive women were at increased risk of subfertility, even when on antiretroviral therapy. Both male and female HIV status were associated with subfertility. Subfertility is an underrecognized reproductive health problem in resource-limited settings and may contribute to prolonged HIV exposure and transmission within couples. Low-cost approaches for screening and treating subfertility in this population are needed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Rationale: Impaired lung function is a potent independent predictor of coronary artery disease (CAD) in individuals without human immunodeficiency virus (HIV) infection; however, the relationship between lung function and CAD in HIV remains undefined. Objectives: To examine the relationship between lung function, CAD, mortality, and circulating biomarkers in HIV. Methods: Spirometry, diffusing capacity of the lung for carbon monoxide (Dl CO ), emphysema, coronary artery calcium, mortality, cause of death, and biomarkers were examined in HIV-infected and uninfected individuals enrolled in a cohort study at the University of Pittsburgh. Results were then validated in the Multicenter AIDS Cohort Study (MACS) cohort. Results: We examined data on 234 participants in the Pittsburgh cohort. The mean ± standard deviation age was 49.5 ± 10.2 years old, 82.1% were male, and 67.5% were ever smokers. Among the 177 of 234 individuals with HIV infection, lower Dl CO (not forced expiratory volume in 1 second or emphysema) was independently associated with greater coronary artery calcium (odds ratio, 1.43 per 10% lower Dl CO ; 95% confidence interval, 1.14-1.81). HIV-infected individuals with both reduced Dl CO and coronary artery calcium had a much higher mortality than those with either low Dl CO or coronary calcium alone or with neither condition. Endothelin-1, a circulating biomarker of endothelial dysfunction, was associated with both lower Dl CO and greater coronary artery calcium in those with HIV infection. Results were reproducible in 144 individuals enrolled in the MACS cohort; intercellular adhesion molecule 1 was the biomarker of endothelial dysfunction assessed in the MACS cohort. Conclusions: Impaired Dl CO and CAD were associated with each other and with higher mortality in individuals with HIV infection.

Objective: To evaluate plasma acylcarnitine profiles and their relationships with progression of carotid artery atherosclerosis among individuals with and without HIV infection., Design: Prospective cohort studies of 499 HIV-positive and 206 HIV-negative individuals from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study., Methods: Twenty-four acylcarnitine species were measured in plasma samples of participants at baseline. Carotid artery plaque was assessed using repeated B-mode carotid artery ultrasound imaging in 2004-2013. We examined the associations of individual and aggregate short-chain (C2-C7), medium-chain (C8-C14) and long-chain acylcarnitines (C16-C26) with incident carotid artery plaque over 7 years., Results: Among 24 acylcarnitine species, C8-carnitines and C20 : 4-carnitines showed significantly lower levels comparing HIV-positive to HIV-negative individuals (false discovery rate adjusted P < 0.05); and C20-carnitines and C26-carnitines showed significantly higher levels in HIV positive using antiretroviral therapy than those without antiretroviral therapy (false discovery rate adjusted P < 0.05). In the univariate analyses, higher aggregated short-chain and long-chain acylcarnitine scores were associated with increased risk of carotid artery plaque [risk ratios (RRs) = 1.22 (95% confidence interval 1.02-1.45) and 1.20 (1.02-1.41) per SD increment, respectively]. The association for the short-chain acylcarnitine score remained significant [RR = 1.23 (1.05-1.44)] after multivariate adjustment (including traditional cardiovascular disease risk factors). This association was more evident in HIV-positive individuals without persistent viral suppression [RR = 1.37 (1.11-1.69)] compared with those with persistent viral suppression during follow-up [RR = 1.03 (0.76-1.40)] or HIV-negative individuals [RR = 1.02 (0.69-1.52)]., Conclusion: In two HIV cohorts, plasma levels of most acylcarnitines were not significantly different between HIV-positive and HIV-negative individuals. However, higher levels of aggregated short-chain acylcarnitines were associated with progression of carotid artery atherosclerosis.

Background: Ceramides have been implicated in the pathophysiology of HIV infection and cardiovascular disease. However, no study, to our knowledge, has evaluated circulating ceramide levels in association with subclinical cardiovascular disease risk among HIV-infected individuals., Methods: Plasma levels of 4 ceramide species (C16:0, C22:0, C24:0, and C24:1) were measured among 398 women (73% HIV+) and 339 men (68% HIV+) without carotid artery plaques at baseline from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. We examined associations between baseline plasma ceramides and risk of carotid artery plaque formation, assessed by repeated B-mode carotid artery ultrasound imaging over a median 7-year follow-up., Results: Plasma levels of C16:0, C22:0, and C24:1 ceramides were significantly higher in HIV-infected individuals compared with those without HIV infection (all P<0.001), and further analysis indicated that elevated ceramide levels were associated with antiretroviral therapy use, particularly protease inhibitor use, in HIV-infected individuals (all P<0.001). All 4 ceramides were highly correlated with each other ( r=0.70-0.94; all P<0.001) and significantly correlated with total-cholesterol ( r=0.42-0.58; all P<0.001) and low-density lipoprotein cholesterol ( r=0.24-0.42; all P<0.001) levels. Of note, C16:0 and C24:1 ceramides, rather than C22:0 and C24:0 ceramides, were more closely correlated with specific monocyte activation and inflammation markers (eg, r=0.30 between C16:0 ceramide and soluble CD14; P<0.001) and surface markers of CD4 + T-cell activation. A total of 112 participants developed carotid artery plaques over 7 years, and higher levels of C16:0 and C24:1 ceramides were significantly associated with increased risk of carotid artery plaques (relative risk [95% CI]=1.55 [1.29, 1.86] and 1.51 [1.26, 1.82] per standard deviation increment, respectively; both P<0.001), after adjusting for demographic and behavioral factors. After further adjustment for cardiovascular disease risk factors and immune activation markers, these associations were attenuated but remained significant. The results were consistent between men and women and between HIV-infected and HIV-uninfected participants., Conclusions: In 2 HIV cohorts, elevated plasma levels of C16:0 and C24:1 ceramides, correlating with immune activation and inflammation, were associated with antiretroviral therapy use and progression of carotid artery atherosclerosis.

Background: HIV-infected persons have an increased risk of atherosclerosis relative to uninfected individuals. Inflammatory processes may contribute to this risk. We evaluated the associations of 10 biomarkers of systemic inflammation (CRP, IL-6, sTNF-αR1 and 2), monocyte activation (CCL2, sCD163, sCD14), coagulation (fibrinogen, D-dimer), and endothelial dysfunction (ICAM-1) with subclinical carotid atherosclerosis among participants in the Multicenter AIDS Cohort Study (MACS)., Methods: Carotid plaque and intima media thickness (IMT) in the common carotid (CCA-IMT) and bifurcation region were assessed by B mode ultrasound among 452 HIV-infected and 276 HIV-uninfected men from 2010-2013. Associations between levels of each biomarker and presence of focal plaque and IMT were assessed by logistic and linear regression models, adjusting for demographics, risk behaviors, traditional cardiovascular disease (CVD) risk factors, and HIV disease characteristics., Results: Compared to HIV-uninfected men, HIV-infected men had significantly higher levels of 8 of the 10 biomarkers. Overall, men with sCD163, CCL2, IL-6, and CRP levels in the highest quintile had approximately 2 times the odds of carotid plaque relative to those with levels in the lowest quintile, independent of demographic and CVD risk factors. Fibrinogen levels were positively associated with CCA-IMT while ICAM-1, CCL2, and sTNF-αR1 levels were positively associated with bifurcation-IMT. Among HIV-uninfected men, higher levels of sTNF-αR2 were positively associated with CCA-IMT, fibrinogen with bifurcation-IMT and carotid plaque, and ICAM-1 with carotid plaque., Conclusion: In addition to greater levels of systemic inflammation, heightened monocyte activation (sCD163, CCL2) may contribute to the burden of atherosclerosis among HIV-infected persons., Competing Interests: FJP is a consultant and/or on the speakers bureau for Gilead, Janssen, ViiV and Merck. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: HIV-infected (HIV+) individuals may be at increased risk for sudden arrhythmic cardiac death. Some studies have reported an association between HIV infection and prolongation of the electrocardiographic QT interval, a measure of ventricular repolarisation, which could potentiate ventricular arrhythmias. We aimed to assess whether HIV+ men have longer QT intervals than HIV-uninfected (HIV-) men and to determine factors associated with QT duration., Methods: We performed resting 12-lead ECGs in 774 HIV+ and 652 HIV- men in the Multicenter AIDS Cohort Study (MACS). We used multivariable linear and logistic regression analyses to assess associations between HIV serostatus and Framingham corrected QT interval (QTc), after accounting for potential confounders. We also determined associations among QTc interval and HIV-related factors in HIV+ men. In a subgroup of participants, levels of serum markers of inflammation were also assessed., Results: After adjusting for demographics and risk factors, QTc was 4.0 ms longer in HIV+ than HIV- men (p<0.001). Use of antiretroviral therapy (ART), specific ART drug class use and other HIV-specific risk factors were not associated with longer QTc. Among the subgroup with inflammatory biomarker measurements, higher interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and B-cell activating factor levels were independently associated with longer QTc and their inclusion partially attenuated the HIV effect., Conclusions: HIV+ men had longer QTc, which was associated with higher levels of systemic inflammatory factors. This longer QTc may contribute to the increased risk for sudden arrhythmic cardiac death in some HIV+ individuals., Competing Interests: Competing interests: FJP is on the speaker’s bureau for Gilead Sciences, Janssen Pharmaceuticals, Merck & Co, Inc and Bristol‐Myers Squibb. MJB has received grants from General Electric Company. TTB has served as a consultant to Gilead Sciences, Merck, Theratechnologies and EMD-Serono., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: GlycA, a novel NMR biomarker of inflammation, has been associated with incident cardiovascular disease (CVD) in the general population, but its association with CVD among HIV-infected individuals is unknown. We examined the associations between GlycA and subclinical coronary plaque among HIV-infected and HIV-uninfected men participating in Multicenter AIDS Cohort Study (MACS)., Design: Cross-sectional analysis of 935 men with plasma measurement of GlycA and noncontrast cardiac computed tomography (CT) and/or coronary CT angiography., Methods: We used multivariable Poisson and linear regression to assess associations of GlycA with prevalent coronary atherosclerosis and plaque extent, respectively., Results: Mean ± SD age was 54 ± 7 years; 31% were black; 63% HIV-infected. GlycA levels were higher in HIV-infected compared with HIV-uninfected men (397 ± 68 vs. 380 ± 60 μmol/l, P = 0.0001) and higher for men with detectable viral load vs. undetectable (413 ± 79 vs. 393 ± 65 μmol/l, P = 0.004). After adjusting for HIV serostatus, demographic and CVD risk factors, every 1SD increment in GlycA level was associated with a higher prevalence of coronary artery calcium (CAC >0) [prevalence ratio 1.09 (95% CI 1.03-1.15)] and coronary stenosis at least 50% [1.20 (1.02-1.41)]. These associations were not significantly altered after adjusting for traditional inflammatory biomarkers or differ by HIV serostatus. Among men with plaque, GlycA was positively associated with the extent of CAC and total plaque., Conclusion: HIV infection was associated with higher GlycA levels. In both HIV-infected and HIV-uninfected individuals, GlycA was significantly associated with several measures of subclinical coronary atherosclerosis, independent of other CVD risk factors and inflammatory biomarkers. These findings suggest the potential role of GlycA in CVD risk stratification among HIV patients.

Objective: Ongoing HIV replication while receiving combination antiretroviral therapy (cART) may reduce survival. Viremia copy-years (VCY) has shown improved mortality risk prediction over single time-point viral load measures. However, the timing of a patient's viral load history most associated with later mortality has not been studied. Here we determined the optimal duration and temporality of viral load history for predicting mortality., Design: Survival analysis among HIV-positive men who initiated cART in the Multicenter AIDS Cohort Study (1995-2015)., Methods: VCY measures were derived from area-under-the-viral load-curve. The overall VCY based upon the complete post-cART viral load history was compared with 20 VCYs derived from viral loads assessed during different shorter time periods (the most recent 1-10 years and initial 1-10 years following cART initiation) for associations with mortality., Results: Each 10-fold increase in VCYs based on the most recent 3-8 years was significantly associated with 23-26% decrease in survival times, a magnitude of effect greater than that of the most recent viral load (16%). These associations were independent of CD4 cell count and single time-point viral loads. In addition, the degree of pre-cART immunodeficiency did not affect the mortality prognostic value of VCY based on viral loads in the most recent 3 years. Conversely, the overall VCY and VCYs based on viral loads immediately following cART initiation were not independent predictors of mortality., Conclusion: Among cART-treated men, VCY based upon viral loads in the recent 3 years (six viral loads) has a mortality prognostic value greater than that of the overall VCY and single time-point viral loads, making the former a more feasible measure for use.

Objective: Among people with HIV, there are few long-term studies of noninvasive ultrasound-based measurements of the carotid artery predicting major health events. We hypothesized that such measurements are associated with 10-year mortality in the Women's Interagency HIV Study (WIHS) and Multicenter AIDS Cohort Study (MACS), and that associations differ by HIV serostatus., Design: Nested cohort study., Methods: Participants without coronary heart disease underwent B-mode carotid artery ultrasound, with measurement of common carotid artery intima-media thickness (IMT); carotid artery plaque (focal IMT > 1.5 mm) at six locations; and Young's modulus of elasticity, a measure of arterial stiffness. We examined all-cause mortality using Cox models, controlling for demographic, behavioral, cardiometabolic, and HIV-related factors., Results: Among 1722 women (median age 40 years, 90% nonwhite, 71% HIV-positive) and 1304 men (median age 50, 39% nonwhite, 62% HIV-positive), 11% died during follow-up. Mortality was higher among HIV-positive women [19.9 deaths/1000 person-years, 95% confidence interval (CI) 14.7-28.8] than HIV-positive men (15.1/1000, 95% CI 8.3-26.8). In adjusted analyses, plaque was associated with mortality (hazard ratio 1.44, 95% CI 1.10-1.88) regardless of HIV serostatus, and varied by sex (among women, hazard ratio 1.06, 95% CI 0.74-1.52; among men; hazard ratio 2.19, 95% CI 1.41-3.43). The association of plaque with mortality was more pronounced among HIV-negative (hazard ratio 3.87, 95% 1.95-7.66) than HIV-positive participants (hazard ratio 1.35, 95% CI 1.00-1.84). Arterial stiffness was also associated with mortality (hazard ratio 1.43 for highest versus lowest quartile, 95% CI 1.02-2.01). Greater common carotid artery-IMT was not associated with mortality., Conclusion: Carotid artery plaque was predictive of mortality, with differences observed by sex and HIV serostatus.

We examined associations of 5 plasma choline metabolites with carotid plaque among 520 HIV-infected and 217 HIV-uninfected participants (112 incident plaque cases) over 7 years. After multivariable adjustment, higher gut microbiota-related metabolite trimethylamine-N-oxide (TMAO) was associated with an increased risk of carotid plaque in HIV-infected participants (risk ratio = 1.25 per standard deviation increment; 95% confidence interval, 1.05-1.50; P = .01). TMAO was positively correlated with biomarkers of monocyte activation and inflammation (sCD14, sCD163). Further adjustment for these biomarkers attenuated the association between TMAO and carotid plaque (P = .08). Among HIV-infected individuals, plasma TMAO was associated with carotid atherosclerosis progression, partially through immune activation and inflammation.

Background: It is unknown whether disrupted tryptophan catabolism is associated with cardiovascular disease (CVD) in human immunodeficiency virus (HIV)-infected individuals., Methods: Plasma tryptophan and kynurenic acid were measured in 737 women and men (520 HIV+, 217 HIV-) from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. Repeated B-mode carotid artery ultrasound imaging was obtained from 2004 through 2013. We examined associations of baseline tryptophan, kynurenic acid, and kynurenic acid-to-tryptophan (KYNA/TRP) ratio, with risk of carotid plaque., Results: After a 7-year follow-up, 112 participants developed carotid plaque. Compared to those without HIV infection, HIV-infected participants had lower tryptophan (P < .001), higher KYNA/TRP (P = .01), and similar kynurenic acid levels (P = .51). Tryptophan, kynurenic acid, and KYNA/TRP were correlated with T-cell activation (CD38+HLA-DR+) and immune activation markers (serum sCD14, galectin-3) but had few correlations with interleukin-6, C-reactive protein, or CVD risk factors (blood pressure, lipids). Adjusted for demographic and behavioral factors, each standard deviation (SD) increment in tryptophan was associated with a 29% (95% confidence interval [CI], 17%-38%) decreased risk of carotid plaque (P < .001), while each SD increment in kynurenic acid (P = .02) and KYNA/TRP (P < .001) was associated with a 34% (6%-69%) and a 47% (26%-73%) increased risk of carotid plaque, respectively. After further adjustment for CVD risk factors and immune activation markers, these associations were attenuated but remained significant., Conclusions: Plasma tryptophan-kynurenine metabolites are altered in HIV infection and associated with progression of carotid artery atherosclerosis.

Background and Aim: The association of HIV with coronary atherosclerosis has been established; however, the progression of coronary atherosclerosis over time among participants with HIV is not well known. The Multicenter AIDS Cohort Study Quantitative Coronary Plaque Progression Study is a large prospective multicenter study quantifying progression of coronary plaque assessed by serial coronary computed tomography angiography (CTA)., Patients and Methods: HIV-infected and uninfected men who were enrolled in the Multicenter AIDS Cohort Study Cardiovascular Substudy were eligible to complete a follow-up contrast coronary CTA 3-6 years after baseline. We measured coronary plaque volume and characteristics (calcified and noncalcified plaque including fibrous, fibrous-fatty, and low attenuation) and vulnerable plaque among HIV-infected and uninfected men using semiautomated plaque software to investigate the progression of coronary atherosclerosis over time., Conclusion: We describe a novel, large prospective multicenter study investigating incidence, transition of characteristics, and progression in coronary atherosclerosis quantitatively assessed by serial coronary CTAs among HIV-infected and uninfected men.