Co-Utilization of HIV, Substance Use, Mental Health Services Among Women With Current Substance Use: Opportunities for Integrated Care?

BACKGROUND: The syndemic of HIV, substance use (SU), and mental illness has serious implications for HIV disease progression among women. We described co-utilization of HIV care, SU treatment, and mental health treatment among women with or at risk for HIV. METHODS: We included data from women with or at risk for HIV (n = 2559) enrolled in all 10 sites of the Women's Interagency HIV Study (WIHS) from 2013 to 2020. Current SU was defined as self-reported, non-medical use of drugs in the past year, excluding use of only marijuana. Tobacco and alcohol were assessed separately. We described co-utilization of SU treatment, tobacco and alcohol use treatment, HIV care, and mental health care in the past year among women who were eligible for each service. We compared service utilization by those who did/did not utilize SU treatment using Wald Chi-square tests. RESULTS: Among women with current SU (n = 358), 42% reported utilizing SU treatment. Among those with current SU+HIV (n = 224), 84% saw their HIV provider, and 34% saw a mental health provider. Among women with current SU+heavy alcohol use (n = 95), 18% utilized alcohol use treatment; among current SU+tobacco use (n = 276), 8% utilized tobacco use treatment. Women who utilized SU treatment had higher utilization of alcohol use treatment (59% vs. 5%; P < .001) and tobacco use treatment (12% vs. 5%; P = .028). HIV care engagement was high regardless of SU treatment. CONCLUSIONS: We found high engagement in SU and HIV care, but low engagement in alcohol and tobacco use treatment. Integrated SU treatment services for women, including tobacco/alcohol treatment and harm reduction, are needed to optimize treatment engagement and HIV care continuum outcomes.

Psychometric Assessment of a Homophobia Management Scale Among Cisgender Sexual Minority Men in Midlife and Older Adulthood.

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.

Associations of Partnership Types and Quality on Cognitive Performance Among Midlife and Older Sexual Minority Men With or Without HIV.

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 ß ^ = 0.41 [95% CI 0.12-0.70]), TMT-A ( ß ^ = 0.16 [95% CI 0.02-0.30]), and TMT-B ( ß ^ = 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.

Consequences of low-level viremia among women with HIV in the United States.

OBJECTIVE: Investigate the outcomes of women with HIV (WWH) with low-level viremia (LLV). DESIGN: The prevalence of LLV and potential clinical sequelae, such as virologic failure and non-AIDS comorbidity (NACM) development, are poorly characterized among WWH. METHODS: We analyzed data from the Women's Interagency HIV Study among WWH enrolled from 2003 to 2020 who reported antiretroviral therapy use at least 1 year followed by an HIV-1 viral load less than 200 copies/ml. Consecutive viral load measurements from four semi-annual visits were used to categorize women at baseline as having: virologic suppression (all viral load undetectable), intermittent LLV (iLLV; nonconsecutive detectable viral load up to 199 copies/ml), persistent LLV (pLLV; at least two consecutive detectable viral load up to 199 copies/ml), or virologic failure (any viral load ≥200 copies/ml). Adjusted hazard ratios quantified the association of virologic category with time to incident virologic failure and multimorbidity (≥2 of 5 NACM) over 5-year follow-up. RESULTS: Of 1598 WWH, baseline median age was 47 years, 64% were Black, 21% Hispanic, and median CD4 + cell count was 621 cells/µl. After excluding 275 women (17%) who had virologic failure at baseline, 58, 19, and 6% were categorized as having virologic suppression, iLLV, and pLLV, respectively. Compared with WWH with virologic suppression, the adjusted hazard ratio [aHR; 95% confidence interval (CI)] for incident virologic failure was 1.88 (1.44-2.46) and 2.51 (1.66-3.79) for iLLV and pLLV, respectively; and the aHR for incident multimorbidity was 0.81 (0.54-1.21) and 1.54 (0.88-2.71) for iLLV and pLLV, respectively. CONCLUSION: Women with iLLV and pLLV had an increased risk of virologic failure. Women with pLLV had a trend towards increased multimorbidity risk.

The Relationship between Serving as a Mentor and Depressive Symptoms among Sexual Minority Men in the MACS Healthy Aging Study.

Sexual minority men (SMM) in the US are twice as likely to experience mental health challenges, including depressive symptoms, compared with their heterosexual counterparts. Having a like-mentor, or a sexual minority mentor, is associated with improved mental well-being among SMM mentees. However, few studies have explored the potential benefits to mentors. Using confirmatory factor analysis, we calculated a perceptions of mentoring score that encompasses experiences and beliefs regarding mentoring of SMM from the Healthy Aging Substudy of the Multicenter AIDS Cohort Study. We used a generalized estimating equations model to assess associations between perceptions of mentoring and clinically significant depressive symptoms adjusted for key covariates; models were also stratified by HIV serostatus. Among 1,246 men aged 40+ years, the strongest agreement was with the statement "I have encouraged people to be proud of their sexual orientation," for which 770 individuals (72%) indicated "Agree" or "Strongly Agree." Each unit increase in the mean perceptions of mentoring score was associated with 8% decreased odds of having clinically significant depressive symptoms (adjusted odds ratio: 0.92; 95% CI: 0.85-0.99). We show that SMM reported like-mentoring experiences and had positive mentoring beliefs, and that these were associated with a decreased odds of having depressive symptoms. Encouraging SMM to serve as like-mentors could be a way to counter depressive symptoms among this key population. There is a need for increased research regarding how mentoring programs can best be designed to benefit sexual minority mentees and mentors.

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.

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

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

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

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

Correction: The longitudinal impact of employment, retirement and disability status on depressive symptoms among men living with HIV in the Multicenter AIDS Cohort Study.

[This corrects the article DOI: 10.1371/journal.pone.0239291.].

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.

Microbial Translocation and Gut Damage Are Associated With an Elevated Fast Score in Women Living With and Without HIV.

Background: Steatohepatitis is common in persons living with HIV and may be associated with gut microbial translocation (MT). However, few studies have evaluated the gut-liver axis in persons living with HIV. In the Women's Interagency HIV Study, we examined the associations of HIV and circulating biomarkers linked to MT and gut damage using the FibroScan-aspartate aminotransferase (FAST) score, a noninvasive surrogate for steatohepatitis with advanced fibrosis. Methods: Among 883 women with HIV and 354 without HIV, we used multivariable regression to examine the associations of HIV and serum biomarkers linked to MT and gut damage (kynurenine and tryptophan ratio, intestinal fatty acid-binding protein, soluble CD14, and soluble CD163) with a log-transformed FAST score after adjusting for key covariates. We used a path analysis and mediation models to determine the mediating effect of each biomarker on the association of HIV with FAST. Results: HIV infection was associated with a 49% higher FAST score. MT biomarker levels were higher in women with HIV than women without HIV (P < .001 for each). MT biomarkers mediated 13% to 32% of the association of HIV and FAST score. Conclusions: Biomarkers linked to MT and gut damage are associated with a higher FAST score and mediate the association of HIV with a higher FAST score. Our findings suggest that MT may be an important mechanism by which HIV increases the risk of steatohepatitis with advanced fibrosis.

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.

Incidence of erectile dysfunction among middle-aged and aging sexual minority men living with or without HIV.

Introduction: Erectile dysfunction (ED) has been established as a comorbidity among men living with HIV, but comparisons by HIV serostatus of ED incidence in a longitudinal follow-up cohort of men are lacking. We sought to evaluate the incidence of ED spanning a period of 12 years in a longitudinal cohort of sexual minority men (SMM) living with and without HIV. Methods: We analyzed ED incidence data for 625 participants in the longitudinal Multicenter AIDS Cohort Study from visits spanning October 2006 to April 2019. Results: SMM living with HIV were more likely to have incident ED compared with those living without HIV (rate ratio: 1.41; 95% CI: 1.14-1.75). Older age, current diabetes, cumulative cigarette use, and cumulative antidepressant use were associated with increased incidence of ED in the entire sample. Self-identifying as Hispanic, current diabetes, and cumulative antidepressant use were positively associated with ED incidence among SMM living with HIV. Cumulative cigarette use was positively associated with greater ED incidence only among SMM living without HIV. Discussion: In summary, age (full sample/ with HIV), current diabetes (full sample/with HIV), cumulative cigarette use (full sample/without HIV), and cumulative antidepressant use (full sample/with HIV) were associated with increased ED incidence. Skillful management of diabetes and careful titration of antidepressants, along with smoking cessation practices, are recommended to mitigate ED in this population.

Association of Androgen Hormones, Sex Hormone-Binding Globulin, and the Menopausal Transition With Incident Diabetes Mellitus in Women With and Without HIV.

BACKGROUND: HIV is associated with alterations in androgen hormone levels and sex hormone-binding globulin (SHBG) in women. Higher SHBG has been associated with a lower risk of diabetes in the general population, but the contribution of HIV, androgen hormones, SHBG, and menopausal phase to diabetes is unclear. METHODS: From April 2003 through February 2020, 896 women with HIV (WWH) and 343 women without HIV (WWOH) from the Women's Interagency HIV Study with morning total testosterone, dehydroepiandrosterone sulfate (DHEAS), and SHBG levels were followed to assess for incident diabetes. Parametric regression models were used with age as the time scale and relative times (RT) as the measure of association of hormone level and menopausal phase with incident diabetes. Analyses incorporated time-dependent androgen hormone, SHBG levels, and menopausal phase and were adjusted for race/ethnicity, enrollment year, smoking status, BMI, hepatitis C virus status, and HIV-related factors. RESULTS: In total, 128 (14%) WWH and 47 (14%) WWOH developed diabetes. In WWH, a doubling of SHBG and DHEAS were associated with a 7% (RT = 1.07 [95% CI: 0.82 to 1.40] and 15% (RT = 1.15 [95% CI: 0.95 to 1.39]) longer time to diabetes, respectively; in WWOH, a doubling of SHBG and DHEAS were associated with 84% (RT = 1.84 [95% CI: 0.89 to 3.82]) and 41% (RT= 1.41 [95% CI: 0.82 to 2.44]) longer times to diabetes. Total testosterone was not associated. In WWH, later menopausal phase was associated with shorter times to diabetes. CONCLUSIONS: Despite alterations in androgen hormone and SHBG levels in HIV, regardless of HIV status, higher SHBG and DHEAS were associated with nonstatistically significant slower progression to diabetes. The menopausal transition may be a better hormonal indicator of diabetes risk in WWH.

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.

Nicotine Metabolite Ratio Decreases After Switching Off Efavirenz-Based Therapy in People With HIV Who Smoke.

Rates of cigarette smoking in people with HIV (PWH) are two to three times higher than in people without HIV. Nicotine is metabolized by CYP2A6 and the nicotine metabolite ratio (NMR; 3-hydroxycotinine/cotinine) is a measure of nicotine clearance. Higher NMR has been observed in PWH and is associated with lower quit rates. Efavirenz, a mainstay antiretroviral therapy (ART) globally, partially upregulates its own metabolism through CYP2A6. We hypothesized that efavirenz also upregulates nicotine metabolism by CYP2A6, resulting in a higher NMR, and switching to non-efavirenz ART would decrease the NMR, potentially leading to improved quit rates. We compared the NMR during and after efavirenz use among PWH in a longitudinal, multisite cohort. Eligibility criteria included: (i) active cigarette smoking, (ii) ART switched from efavirenz-based to non-efavirenz-based regimen, (iii) plasma available at pre- and post-ART switch, and (iv) viral suppression during study period. Plasma cotinine and 3-hydroxycotinine were measured by liquid chromatography-tandem mass spectrometry. T-tests compared the NMR on and off efavirenz. Samples were collected between 2010 and 2019 in 72 PWH. The mean NMR difference after switching to a non-efavirenz-based regimen was -0.24 (SD: 0.37, P < 0.001); 44 PWH had at least a 0.1 decrease in NMR. Effect modification by race was present; Black PWH had a larger mean decrease. Our findings suggest that previously observed higher NMR among PWH may be due to direct pharmacologic effects of ART. Assessing the effect of ART on the NMR suggests that avoiding nicotine metabolism inducers could potentially increase quit rates.

Life course history of physical and sexual abuse is associated with cardiovascular disease risk among women living with and without HIV.

OBJECTIVE: Sexual and physical abuse predict cardiovascular disease (CVD) among women in the general population. Women living with HIV (WLWH) report more abuse and have higher CVD risk compared with other women, yet associations between abuse history and CVD have not been considered among WLWH. This study fills this gap, and describes possible pathways linking abuse to CVD risk among WLWH and women living without HIV (WLWOH). METHODS: Using 25 years of data from the Women's Interagency HIV Study (WIHS; n  = 2734; WLWH n  = 1963; WLWOH n  = 771), we used longitudinal generalized estimating equations (GEE) to test associations between sexual and physical abuse with CVD risk. Framingham (FRS-H) and the American College of Cardiology/American Heart Association-Pooled Cohort Equation (ACC/AHA-PCE) scores were examined. Analyses were stratified by HIV-serostatus. RESULTS: Among WLWH, childhood sexual abuse was associated with higher CVD risk ( ßFRS-H  = 1.25, SE = 1.08, P  = 0.005; ßACC/AHA-PCE  = 1.14, SE = 1.07, P  = 0.04) compared with no abuse. Adulthood sexual abuse was associated with higher CVD risk for WLWH ( ßFRS-H  = 1.39, SE = 1.08, P  < 0.0001) and WLWOH ( ßFRS-H  = 1.58, SE = 1.14, P  = 0.0006). Childhood physical abuse was not associated with CVD risk for either group. Adulthood physical abuse was associated with CVD risk for WLWH ( ßFRS-H  = 1.44, SE = 1.07; P  < 0.0001, ßACC/AHA-PCE  = 1.18, SE = 1.06, P  = 0.002) and WLWOH ( ßFRS-H  = 1.68, SE = 1.12, P  < 0.0001; ßACC/AHA-PCE  = 1.24, SE = 1.11, P  = 0.03). Several pathway factors were significant, including depression, smoking, and hepatitis C infection. CONCLUSION: Life course abuse may increase CVD risk among WLWH and women at high risk of acquiring HIV. Some comorbidities help explain the associations. Assessing abuse experiences in clinical encounters may help contextualize cardiovascular risk among this vulnerable population and inform intervention.

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.

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.