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.

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.

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

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

Gut Microbiota, Plasma Metabolomic Profiles, and Carotid Artery Atherosclerosis in HIV Infection.

BACKGROUND: Alterations in gut microbiota and blood metabolomic profiles have been implicated in HIV infection and cardiovascular disease. However, it remains unclear whether alterations in gut microbiota may contribute to disrupted host blood metabolomic profiles in relation to atherosclerosis, especially in the context of HIV infection. METHODS: We analyzed cross-sectional associations between gut microbiota features and carotid artery plaque in 361 women with or at high risk of HIV (67% HIV+), and further integrated plaque-associated microbial features with plasma lipidomic/metabolomic profiles. Furthermore, in 737 women and men, we examined prospective associations of baseline gut bacteria-associated lipidomic and metabolomic profiles with incident carotid artery plaque over 7-year follow-up. RESULTS: We found 2 potentially pathogenic bacteria, Fusobacterium and Proteus, were associated with carotid artery plaque; while the beneficial butyrate producer Odoribacter was inversely associated with plaque. Fusobacterium and Proteus were associated with multiple lipids/metabolites which were clustered into 8 modules in network. A module comprised of 9 lysophosphatidylcholines and lysophosphatidylethanolamines and a module comprised of 9 diglycerides were associated with increased risk of carotid artery plaque (risk ratio [95% CI], 1.34 [1.09-1.64] and 1.24 [1.02-1.51] per SD increment, respectively). Functional analyses identified bacterial enzymes in lipid metabolism associated with these plasma lipids. In particular, phospholipase A1 and A2 are the key enzymes in the reactions producing lysophosphatidylcholines and lysophosphatidylethanolamines. CONCLUSIONS: Among individuals with or at high risk of HIV infection, we identified altered gut microbiota and related functional capacities in the lipid metabolism associated with disrupted plasma lipidomic profiles and carotid artery atherosclerosis.

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

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

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

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

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

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

Grit is associated with psychological health among older sexual minority men.

Objectives: Studies have shown that grit-defined as perseverance and passion for achieving one's long-term goals-is associated with improved health outcomes, including lower levels of psychological distress. However, the psychometric properties of the original Grit Scale (Grit-O Scale) has not been validated among sexual minority men (SMM). The present study aimed to validate the Grit-O Scale among a sample of older SMM and assess the relationships between the Grit-O Scale factors and symptoms of psychological distress.Method: We used data from a single visit of participants in the Multicenter AIDS Cohort Study (MACS) Healthy Aging longitudinal study. The sample included 981 older SMM (mean age = 61, SD = 8.5) with and without HIV. We conducted confirmatory factor analysis (CFA) to identify the two factors of the Grit-O Scale: consistency of interest and perseverance of effort. We also conducted a latent profile analysis (LPA) to identify distinct profiles of psychological distress from self-reported scales of depression, anxiety, and perceived stress.Results:The Grit-O Scale showed acceptable reliability estimates for the items with Cronbach's alpha reliability coefficients ranging from 0.77 to 0.82. The CFA identified the two factors of the Grit-O Scale with acceptable model fit (root mean square error of approximation = 0.058 [95% CI = 0.050, 0.067], comparative fit index = 0.95, Tucker-Lewis Index = 0.93, standardized root mean square residual = 0.07). The LPA yielded three mutually exclusive profiles of psychological distress (profile 1: low stress, anxiety, and depression; profile 2: high stress and depression and low anxiety; and profile 3: high stress, anxiety, and depression). In adjusted multinominal logistic regression analysis, we found that both higher levels of consistency of interest and perseverance of effort factors of the Grit-O Scale were significantly associated with decreased odds of being in profiles 2 and 3 compared with being in profile 1.Conclusion: Our findings support the use of the Grit-O Scale among older SMM. Grit factors could explain variability in the negative psychological symptoms among older SMM and warrant further investigation.Supplemental data for this article is available online at http://dx.doi.org/10.1080/13607863.2022.2032594.

Biopsychosocial Health Outcomes and Experienced Intersectional Stigma in a Mixed HIV Serostatus Longitudinal Cohort of Aging Sexual Minority Men, United States, 2008‒2019.

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).

Circulating biomarker correlates of left atrial size and myocardial extracellular volume fraction among persons living with and without HIV.

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.

Barriers and Facilitators to Effective Implementation of the NAMWEZA Intervention in Dar es Salaam, Tanzania.

The NAMWEZA intervention was implemented, using a ten-session group format, to build skills targeting psychosocial vulnerabilities and enhancing HIV prevention among people living with HIV (PLH) and their social networks. The overall goal of this intervention is to improve psychological wellbeing and reduce HIV risk behaviours. These analyses aim to describe the barriers and facilitators of implementing the NAMWEZA intervention from the perspective of participants and trained peer group facilitators. Twenty-four in-depth interviews were conducted with NAMWEZA participants, and 50 pooled peer facilitator self-assessment reports were obtained from 16 trained peers. Participants identified personal and structural barriers, including fear of inadvertent HIV status disclosure, time constraints, level of participant reimbursements, and limited space available for group sessions. Factors facilitating effective implementation included perceived benefits of the program, such as reduction in HIV-related risk behaviours, increased self-esteem, and improvement in confidence in HIV prevention communications. Scaling up the NAMWEZA intervention to other areas of Tanzania or regionally should take into account these facilitators and barriers to implementation.

Elevated Plasma Ceramides Are Associated With Antiretroviral Therapy Use and Progression of Carotid Artery Atherosclerosis in HIV Infection.

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.

Self-perception of aging among HIV-positive and HIV-negative participants in the Multicenter AIDS Cohort Study.

Self-perception of aging is an important predictor of quality of life. Therefore, we sought to examine self-perceptions of aging (age discrepancy and aging satisfaction) between HIV-positive and HIV-negative men in the Multicenter AIDS Cohort Study (MACS). We included 835 HIV-negative and 784 HIV-positive men aged 50 years and older who had completed a survey about age discrepancy and aging satisfaction from the "Attitude toward own aging" subscale of the Philadelphia Geriatric Center Morale scale. Multinomial generalized logit models were generated to assess self-perception of aging by HIV-status. Most of the participants self-identified as white, former smokers, and had completed high school. HIV-positive individuals reported higher prevalence of comorbidities than HIV-negative individuals. After adjusting for covariates, positive age discrepancy (older subjective age) was positively associated with being HIV-positive and having less than a high school education, depressive symptoms, diabetes, and medium and low aging satisfaction. Low aging satisfaction was associated with being a current and former smoker and having depressive symptoms, diabetes, and no age and positive age discrepancy. Being black had decreased odds of low aging satisfaction. These findings should inform health care professionals to promote positive views of aging in the assessment and management of HIV, depression, and diabetes.

Associations between QT interval subcomponents, HIV serostatus, and inflammation.

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.

Subfertility among HIV-affected couples in a safer conception cohort in South Africa.

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.

Integration of HIV testing services into family planning services: a systematic review.

BACKGROUND: Despite significant interest in integrating sexual and reproductive health (SRH) services into HIV services, less attention has been paid to linkages in the other direction. Where women and girls are at risk of HIV, offering HIV testing services (HTS) during their visits to family planning (FP) services offers important opportunities to address both HIV and unwanted pregnancy needs simultaneously. METHODS: We conducted a systematic review of studies comparing FP services with integrated HTS to those without integrated HTS or with a lower level of integration (e.g., referral versus on-site services), on the following outcomes: uptake/counseling/offer of HTS, new cases of HIV identified, linkage to HIV care and treatment, dual method use, client satisfaction and service quality, and provider knowledge and attitudes about integrating HTS. We searched three online databases and included studies published in a peer-reviewed journal prior to the search date of June 20, 2017. RESULTS: Of 530 citations identified, six studies ultimately met the inclusion criteria. Three studies were conducted in Kenya, and one each in Uganda, Swaziland, and the USA. Most were in FP clinics. Three were from the Integra Initiative. Overall rigor was moderate, with one cluster-randomized trial. HTS uptake was generally higher with integrated sites versus comparison or pre-integration sites, including in adjusted analyses, though outcomes varied slightly across studies. One study found that women at integrated sites were more likely to have high satisfaction with services, but experienced longer waiting times. One study found a small increase in HIV seropositivity among female patients testing after full integration, compared to a dedicated HIV tester. No studies comparatively measured linkage to HIV care and treatment, dual method use, or provider knowledge/attitudes. CONCLUSIONS: Global progress and success for reaching SRH and HIV targets depends on progress in sub-Saharan Africa, where women bear a high burden of both unintended pregnancy and sexually transmitted infections, including HIV. While the evidence base is limited, it suggests that integration of HTS into FP services is feasible and has potential for positive joint outcomes. The success and scale-up of this approach will depend on population needs and health system factors.

Gut Microbial-Related Choline Metabolite Trimethylamine-N-Oxide Is Associated With Progression of Carotid Artery Atherosclerosis in HIV Infection.

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.

Plasma Tryptophan-Kynurenine Metabolites Are Altered in Human Immunodeficiency Virus Infection and Associated With Progression of Carotid Artery Atherosclerosis.

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.

Association of Macrophage Inflammation Biomarkers With Progression of Subclinical Carotid Artery Atherosclerosis in HIV-Infected Women and Men.

Background: Monocytes and monocyte-derived macrophages promote atherosclerosis through increased inflammation and vascular remodeling. This may be especially true in chronic human immunodeficiency virus (HIV) infection. Methods: We examined 778 women (74% HIV+) in the Women's Interagency HIV Study and 503 men (65% HIV+) in the Multicenter AIDS Cohort Study who underwent repeated B-mode carotid artery ultrasound imaging in 2004-2013. We assessed baseline associations of the serum macrophage inflammation markers soluble (s)CD163, sCD14, galectin-3 (Gal-3), and Gal-3 binding protein (Gal-3BP) with carotid plaque formation (focal intima-media thickness >1.5 mm) over 7 years. Results: Marker levels were higher in HIV+ persons versus HIV- persons. Presence of focal plaque increased over time: from 8% to 15% in women, and 24% to 34% in men. After adjustment for demographic, behavioral, and cardiometabolic factors, and CRP and interleukin-6, each standard deviation increase in sCD14 was associated with increased plaque formation (risk ratio [RR] 1.24, 95% confidence interval [CI] 1.07-1.43). This pattern was consistentby sex. sCD163 was associated with plaque formation in virally suppressed HIV+ men (RR 1.52, 95% CI 1.04-2.22); Gal-3BP and Gal-3 were not associated with increased plaque. Conclusions: sCD14 and sCD163 may play important roles in atherogenesis among HIV+ persons.

Integration of Family Planning Services into HIV Care and Treatment Services: A Systematic Review.

Evidence on the feasibility, effectiveness, and cost-effectiveness of integrating family planning (FP) and HIV services has grown significantly since the 2004 Glion Call to Action. This systematic review adds to the knowledge base by characterizing the range of models used to integrate FP into HIV care and treatment, and synthesizing the evidence on integration outcomes among women living with HIV. Fourteen studies met our inclusion criteria, eight of which were published after the last systematic review on the topic in 2013. Overall, integration was associated with higher modern method contraceptive prevalence and knowledge, although there was insufficient evidence to evaluate its effects on unintended pregnancy or achieving safe and healthy pregnancy. Evidence for change in unmet need for FP was limited, although two of the three evaluations that measured unmet need suggested possible improvements associated with integrated services. However, improving access to FP services through integration was not always sufficient to increase the use of more effective (noncondom) modern methods among women who wanted to prevent pregnancy. Integration efforts, particularly in contexts where contraceptive use is low, must address community-wide and HIV-specific barriers to using effective FP methods alongside improving access to information, commodities, and services within routine HIV care.