Inflammatory Markers Associated With Subclinical Coronary Artery Disease: The Multicenter AIDS Cohort Study.

BackgroundDespite evidence for higher risk of coronary artery disease among HIV+ individuals, the underlying mechanisms are not well understood. We investigated associations of inflammatory markers with subclinical coronary artery disease in 923 participants of the Multicenter AIDS Cohort Study (575 HIV+ and 348 HIV- men) who underwent noncontrast computed tomography scans for coronary artery calcification, the majority (n=692) also undergoing coronary computed tomography angiography.Methods and resultsOutcomes included presence and extent of coronary artery calcification, plus computed tomography angiography analysis of presence, composition, and extent of coronary plaques and severity of coronary stenosis. HIV+ men had significantly higher levels of interleukin-6 (IL-6), intercellular adhesion molecule-1, C-reactive protein, and soluble-tumor necrosis factor-α receptor (sTNFαR) I and II (all P<0.01) and a higher prevalence of noncalcified plaque (63% versus 54%, P=0.02) on computed tomography angiography. Among HIV+ men, for every SD increase in log-interleukin-6 and log intercellular adhesion molecule-1, there was a 30% and 60% increase, respectively, in the prevalence of coronary stenosis ≥50% (all P<0.05). Similarly, sTNFαR I and II in HIV+ participants were associated with an increase in prevalence of coronary stenosis ≥70% (P<0.05). Higher levels of interleukin-6, sTNFαR I, and sTNFαR II were also associated with greater coronary artery calcification score in HIV+ men (P<0.01).ConclusionsHigher inflammatory marker levels are associated with greater prevalence of coronary stenosis in HIV+ men. Our findings underscore the need for further study to elucidate the relationships of inflammatory pathways with coronary artery disease in HIV+ individuals

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.This was supported by the National Institute on Minority Health and Health Disparities (grant number R01 MD010680; M.R.F. and M.P.) and the National Institute on Drug Abuse (grant number K01DA047912). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). MACS/WIHS Combined Cohort Study (MWCCS) (Principal Investigators): Atlanta Clinical Research Site (CRS) (Ighovwerha Ofotokun, Anandi Sheth, and Gina Wingood), U01-HL146241; Baltimore CRS (Todd Brown and Joseph Margolick), U01-HL146201; Bronx CRS (Kathryn Anastos and Anjali Sharma), U01-HL146204; Brooklyn CRS (Deborah Gustafson and Tracey Wilson), U01-HL146202; Data Analysis and Coordination Center (Gypsyamber D’Souza, Stephen Gange, and Elizabeth Golub), U01-HL146193; Chicago–Cook County CRS (Mardge Cohen and Audrey French), U01-HL146245; Chicago-Northwestern CRS (Steven Wolinsky), U01-HL146240; Connie Wofsy Women’s HIV Study, Northern California CRS (Bradley Aouizerat, Phyllis Tien, and Jennifer Price), U01-HL146242; Los Angeles CRS (Roger Detels), U01-HL146333; Metropolitan Washington CRS (Seble Kassaye and Daniel Merenstein), U01-HL146205; Miami CRS (Maria Alcaide, Margaret Fischl, and Deborah Jones), U01-HL146203; Pittsburgh CRS (Jeremy Martinson and Charles Rinaldo), U01-HL146208; UAB-MS CRS (Mirjam-Colette Kempf, Jodie Dionne-Odom, and Deborah Konkle-Parker), U01-HL146192; and UNC CRS (Adaora Adimora), U01-HL146194. The MWCCS is funded primarily by the National Heart, Lung, and Blood Institute, with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute on Aging, National Institute of Dental and Craniofacial Research, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Nursing Research, National Cancer Institute, National Institute on Alcohol Abuse and Alcoholism, National Institute on Deafness and Other Communication Disorders, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Minority Health and Health Disparities, and in coordination and alignment with the research priorities of the NIH, Office of AIDS Research. MWCCS data collection is also supported by UL1-TR000004 (University of California, San Francisco Clinical and Translational Science Award), P30-AI-050409 (Atlanta Center for AIDS Research [CFAR]), P30-AI-050410 (UNC CFAR), and P30-AI-027767 (University of Alabama CFAR). This work was also supported by national funds through the FCT–Foundation for Science and Technology, I.P., within the scope of projects UIDB/04750/2020 and LA/P/0064/2020. This study was also supported by a Scientific Employment Stimulus contract to A.H. (CEECIND/01793/2017)

Association of PTSD With Longitudinal COVID-19 Burden in a Mixed-Serostatus Cohort of Men and Women: Weathering the Storm

Objectives:This study of people with HIV (PWH) and those without HIV conducted during the COVID-19 pandemic in the United States in 2020 examines the impact of posttraumatic stress disorder (PTSD) on COVID-19 burden, defined as pandemic-related disruptions.Methods:Data consisted of survey responses on PTSD among participants (N = 2434) enrolled in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV (WIHS) cohorts. Unadjusted and adjusted regression models were used to examine the association of PTSD with COVID-19 burden (overall and domain-specific burdens). Quasi-Poisson regression models were used to assess associations with the COVID-19 burden score and 2 domain-specific burdens: (1) changes in resources and (2) interruptions in health care. Analyses was adjusted for age, race/ethnicity, HIV serostatus, current smoking status, number of comorbidities, education, and study regions.Results:Study participants were a median age of 58 (interquartile range, 52-65) years. In both bivariate and multivariable models, PTSD severity was associated with greater overall COVID-19 burden. PTSD severity was associated with the number of resource changes and number of interruptions in medical care. These findings were also consistent across cohorts (MACS/WIHS) and across HIV serostatus, suggesting a greater risk for COVID-19 burden with greater PTSD severity, which remained significant after controlling for covariates.Conclusions:This study builds on emerging literature demonstrating the impact of mental health on the burden and disruption associated with the COVID-19 pandemic, providing context specific to PWH. The ongoing pandemic requires structural and social interventions to decrease disruption to resources and health resource needs among these vulnerable populations

Sexual and reproductive health and human rights of women living with HIV

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138378/1/jia20834-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138378/2/jia20834.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138378/3/jia20834-sup-0002.pd

Hot electron effects in AlGaN/GaN HEMTs during hard-switching events

This work contains an investigation of hot-electrons effects in GaN transistors during a hard-switching event by means of wafer-level measurements and TCAD mixed-mode hydrodynamic simulations. The latter reveals the presence of hot electrons at the passivation/barrier interface during commutation. Trapping in this location can explain the measured on-state resistance increase during switching operation and leads to a redistribution of the lateral electric field in the two-dimensional electron gas, which in return modulates the hot electron injection process

Hot-Electron Effects in AlGaN/GaN HEMTs under Semi-ON DC Stress

An analysis of hot-electron (HE) effects on the dynamic resistance ( ${dR},_{mathrm{scriptstyle ON}}$ ) of AlGaN/GaN high-electron-mobility transistors (HEMTs) when subject to semi-ON stress is reported and compared with OFF-state stress. This is carried out using measurements and TCAD 2-D hydrodynamic simulations. Two structures with different distances between the highly carbon-doped buffer region and the two-dimensional electron gas (2DEG) are here considered. The additional ${dR},_{mathrm{scriptstyle ON}}$ in semi-ON is attributed to HEs trapping at the passivation/AlGaN interface. TCAD simulations are performed and compared with experimental results

Threshold voltage instabilities in D-mode GaN HEMTs for power switching applications

Threshold voltage instabilities observed in GaN HEMTs designed for power switching applications when submitted to either DC or pulsed testing are here presented and interpreted. Main results can be summarized as follows: i) two acceptor trap levels, characterized by two well distinct time constants, are present in the UID GaN channel and C-doped GaN buffer respectively and behave as electron and hole traps respectively; ii) the trapped charge is modulated by the high voltage biasing of the gate and drain terminals; iii) when empty, channel electron traps induce a negative threshold-voltage shift, while buffer hole traps induce a positive threshold-voltage shift; iv) when the device is pulsed from off-to on-state conditions, trap charge/discharge dynamics induces negative and positive threshold-voltage instabilities over distinct time scales

Drain Field Plate Impact on the Hard-Switching Performance of AlGaN/GaN HEMTs

In this work, an analysis of the impact of drain field plate (FP) length on the semi-ON degradation of AlGaN/GaN high-electron-mobility transistors (HEMTs) is performed. A wafer-level characterization, by means of pulsed stress tests, reveals a faster and more severe decrease of the drain current in the linear region for the samples with longer drain FP. 2-D technology computer-aided design (TCAD) hydrodynamic simulations show that a time and field-dependent hot electrons (HEs) trapping takes place at the passivation/barrier interface. The higher drain current decrease in the longer FP samples can be ascribed to an enhanced HE trapping at the drain FP edge due to a different electric field distribution

Cardiovascular disease risk scores’ relationship to subclinical cardiovascular disease among HIV-infected and HIV-uninfected men

ObjectiveTo study cardiovascular disease risk score utility, we compared the association between Framingham Risk Score (FRS)/pooled cohort equation (PCE) categories and coronary artery plaque presence by HIV serostatus and evaluated whether D : A : D risk category more accurately identifies plaque in HIV-infected men.DesignCross-sectional analysis within a substudy of the Multicenter AIDS Cohort Study.MethodsCardiac computed tomography was performed to assess coronary plaque. We evaluated the association of plaque with increasing cardiovascular disease risk score category, stratified by HIV serostatus, using logistic regression. Receiver operating characteristic curves compared the discrimination of the scores for plaque by HIV serostatus. The sensitivity and specificity of the risk scores were compared in HIV-infected men.ResultsThe risk score category - plaque associations were stronger among HIV-uninfected men than HIV-infected men, except for noncalcified plaque. For example, the odds of coronary artery calcium more than 0 were 7.03 (95% confidence interval 4.21, 11.76) times greater among men in the PCE high-risk versus low-risk category among HIV-uninfected men, compared with just 3.13 (95% confidence interval 2.13, 4.61) times greater among men in the high-risk versus low-risk category among HIV-infected men. Among HIV-infected men, high-risk category by PCE identified the greatest percentage of men with plaque/stenosis, but with lower specificity than D : A : D and FRS. The prevalence of coronary artery calcium more than 0 among men in the PCE low-risk category was 26.5% (HIV-uninfected men) and 36.0% (HIV-infected men).ConclusionsFRS and PCE categories associate with plaque burden better in HIV-uninfected men. No risk score delivered both high sensitivity and specificity among HIV-infected men

HIV Infection Is Associated with Greater Left Ventricular Mass in the Multicenter AIDS Cohort Study.

HIV infection has been associated with diastolic heart failure and atrial fibrillation. The purpose of this study is to determine whether HIV infection is associated with differences in left ventricular mass (LVM), left ventricular end-diastolic volume (LVEDV), and left atrial volume (LAV) indexed to body surface area (left ventricular mass index, left ventricular end-diastolic volume index [LVEDVI], and left atrial volume index [LAVI], respectively). Cross-sectional study of 721 men [425 HIV-infected (HIV+), 296 HIV-uninfected (HIV-) enrolled in the cardiovascular substudy of the Multicenter AIDS Cohort Study (MACS). Participants underwent cardiac computed tomography imaging. A blinded reader measured LVM, LVEDV, and LAV. We used multivariable linear regression models to evaluate whether LVEDVI, left ventricular mass index (LVMI), and LAVI differed by HIV serostatus, adjusting for demographics and cardiovascular disease risk factors. LVMI was significantly greater in HIV+ compared with HIV- men, with adjusted difference of 2.65 g/m2 (95% confidence interval 0.53-4.77, p < .001). Left ventricular end-diastolic index and LAVI did not differ significantly between the two groups. HIV-related factors (nadir CD4 count, clinical AIDS diagnosis, cumulative antiretroviral therapy use, and cumulative protease inhibitor use) were not significantly associated with LVMI, LVEDVI, or LAVI. LVM was significantly higher in HIV+ than HIV- men, which may contribute to the observed increased risk for diastolic heart failure associated with HIV infection. Although HIV infection has been associated with an increased risk for atrial fibrillation, we did not find any difference in LAV by HIV serostatus