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Objective: Diabetes mellitus (DM) is associated with lower antiretroviral (ART) drug exposure among persons with HIV (PWH) compared to PWH without DM. The association between DM and virologic control in PWH, however, remains unknown., Methods: We included participants in the Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study (MWCCS) who had initiated ART between 1999 and 2020 and had a suppressed HIV viral load (≤200 copies/ml) within 1 year of ART initiation. We compared the frequency of incident HIV viremia (HIV-1 RNA >200 copies/ml) between adult PWH with and without DM. Poisson regression was used to examine the rate of incident viremia based on the diagnosis of DM among PWH. DM was defined as two consecutive fasting glucose measurements ≥126 mg/dl, use of antidiabetic medications, preexisting DM diagnosis, or a confirmed HbA1c >6.5%., Results: 1061 women (112 with DM, 949 without DM) and 633 men (41 with DM, and 592 without DM) were included in the analysis. The relative rate (RR) of incident HIV viremia for women with HIV and DM was lower when compared to women without DM (0.85 [95% CI: 0.72-0.99]; P  = 0.04). The RR of incident viremia for women with uncontrolled DM (HbA1c > 7.5%) was higher when compared to women with controlled DM (HbA1c < 7.5%) (1.46 [95% CI: 1.03-2.07]; P  = 0.03). In contrast, the RR of incident viremia for men with HIV and DM was not statistically different compared to men without DM (1.2 [95% CI: 0.96-1.50]; P  = 0.12). The results were stratified by adherence levels (100%, 95-99%, and <95% based on self-report)., Conclusions: Women with DM who are highly adherent to ART (100% self-reported adherence) have a lower risk of viremia compared to women with HIV without DM. However, women with poorly controlled DM were at higher risk of HIV viremia than women with controlled DM. Further research is necessary to understand the impact of sex, DM, and ART adherence on HIV viremia., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: People with HIV (PWH) are at greater risk for diastolic dysfunction compared with persons without HIV (PWOH). An increase in visceral adipose tissue is common among PWH and greater visceral adipose tissue is associated with diastolic dysfunction among PWOH. We investigated associations of visceral adipose tissue, subcutaneous adipose tissue, and other fat depots with subclinical diastolic dysfunction among men with and without HIV (MWH and MWOH)., Design: Cross-sectional analysis of MWH and MWOH in the Multicenter AIDS Cohort Study (MACS)., Methods: Participants underwent echocardiography for diastolic dysfunction assessment and CT scanning including subcutaneous, visceral, epicardial, and liver adiposity measurements. Diastolic dysfunction was defined by characterizing heart function on antiretroviral therapy0 criteria. Odds for diastolic dysfunction with each measure of adiposity were estimated using multivariable logistic regression., Results: Among 403 participants (median age 57, 55% white, median BMI 26 kg/m 2 ), 25% met criteria for diastolic dysfunction and 59% MWH (82% undetectable plasma HIV RNA). Greater epicardial adipose tissue area was associated with higher odds of diastolic dysfunction [odds ratio:1.54 per SD; 95%confidence interval (CI) 1.15-2.05] when adjusted for demographics, HIV serostatus, and cardiovascular risk factors. This association did not differ by HIV serostatus and persisted when excluding MWH who were not virally suppressed. Less subcutaneous adipose tissue was associated with higher odds of diastolic dysfunction. Other adipose depots were not associated with diastolic dysfunction., Conclusion: Greater epicardial adipose tissue and less subcutaneous adipose tissue were associated with diastolic dysfunction, regardless of HIV serostatus and viral suppression. Greater epicardial adipose tissue and less subcutaneous adipose tissue observed among PWH may contribute to risk for heart failure with preserved ejection fraction in this population., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Virally-suppressed people with HIV (VS-PWH) show heterogeneity in patterns of cognitive dysfunction. To better understand the relationship between the neuroimmune response and cognition, we used positron emission tomography (PET) to image the translocator protein 18 kDa (TSPO). The study examined HIV-serostatus differences in TSPO as well as associations between regional TSPO and select cognitive processes defined using the Research Domain Criteria (RDoC) framework., Design: Cross-sectional investigation in VS-PWH (n = 25) versus HIV-uninfected individuals (n = 18) of cognitive control and declarative memory, as well as [11C]DPA-713 PET measures of TSPO within cognitive control and declarative memory regions of interest., Methods: Group differences in [11C]DPA-713 binding (VT) in cognitive control or declarative memory regions were examined using linear mixed models. Tests of associations between factor-derived cognitive system measures and PET measures were performed, controlling for TSPO genotype., Results: There were no group differences in any of the four factor-derived cognitive system measures. VS-PWH had higher log [11C]DPA-713 VT across cognitive control regions(unstandardized beta coefficient reflecting mean difference [B] = 0.23, SE = 0.11, 95% confidence interval [CI] 0.01, 0.45, P = 0.04) and declarative memory regions (B = 0.24, SE = 0.11, 95%CI 0.02, 0.45, P = 0.03). Higher log [11C]DPA-713 VT in cognitive control regions related to poorer cognitive control in each group, and to worse self-reported cognitive performance in VS-PWH. Log [11C]DPA-713 VT in each declarative memory region did not associate with measured declarative memory., Conclusions: A localized neuroimmune response marked by high TSPO in brain regions that subserve cognitive control may contribute to poorer cognitive control in VS-PWH., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Risk factors for progression from prediabetes mellitus (pre-DM) to diabetes mellitus (DM) among people with HIV (PWH) receiving modern antiretroviral therapy (ART) require better characterization., Design: AIDS Clinical Trials Group (ACTG) A5322 (HAILO) was an observational cohort study of PWH ≥40 years old. Participants initiated ART through ACTG randomized clinical trials., Methods: We used Cox proportional hazards regression models to identify risk factors for development of DM among HAILO participants with pre-DM., Results: Among 1035 HAILO participants, 74 (7%) had pre-DM at entry and another 679 (66%) developed pre-DM during follow-up. Of 753 PWH with pre-DM, 167 (22%) developed DM. In multivariable models, the risk of developing DM was greater with higher BMI, lower CD4 count (≤200 cells/mm 3 ), hypertriglyceridemia, or higher waist circumference at pre-DM diagnosis ( P  < 0.01)., Conclusion: Rates of pre-DM and progression to DM remain high among virally suppressed PWH receiving modern ART regimens. Traditional risks for DM, such as higher BMI or waist circumference, are associated with increased risk of incident DM among PWH with pre-DM. The association between lower CD4 + and progression to DM suggests a role for advanced immunodeficiency and inflammation. Further investigation of interventions aimed at preventing DM among PWH with pre-DM is needed. Optimizing prevention and treatment for DM may be an intervenable opportunity to improve long-term outcomes for PWH., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Integrase strand transfer inhibitors (INSTI) are associated with weight gain in people with HIV (PWH), but their impact on diabetes is unclear. We evaluated the association between switching from nonnucleoside reverse-transcriptase inhibitors (NNRTI) or protease inhibitors (PI) to INSTI and incident diabetes., Design: Longitudinal cohort study., Methods: We included PWH aged ≥18 years from the Johns Hopkins HIV Clinical Cohort (2007-2023) without history of diabetes who had used NNRTI or PI for ≥180 days. We followed participants up to 10 years from HIV primary care visits where they switched to INSTI or continued NNRTI or PI. We estimated the hazard of incident diabetes associated with switching to INSTI using weighted Cox regression with robust variance estimator., Results: We included 2075 PWH who attended 22 116 visits where they continued NNRTI or PI and 631 visits where they switched to INSTI. Switching to INSTI was associated with a weighted hazard ratio (wHR) of 1.11 [95% confidence interval (CI), 0.77-1.59] for incident diabetes. The association if no weight gain occurred during the first two years was not qualitatively different (wHR 1.22; 95% CI, 0.82-1.80). In a posthoc analysis, switching to INSTI conferred a significant wHR of 1.79 (95% CI, 1.13-2.84) for diabetes within the first two years but not after., Conclusions: Switching from NNRTI or PI to INSTI did not significantly increase overall diabetes incidence in PWH, although there may be elevated risk in the first two years. These findings can inform considerations when switching to INSTI-based regimens., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: We identify the association between high- and low-intensity case management services on hospital and emergency department (ED) use among CommunityConnect patients., Background: Social needs case management services vary in intensity, including the modality, workforce specialization, and maximum caseload. CommunityConnect is a social needs case management program implemented by Contra Costa Health, a county safety-net health system in California's San Francisco Bay Area., Methods: Due to the endogeneity of high-intensity services assigned to high-risk patients, we instrument for service intensity using the number of specialist case managers hired each month of enrollment. Zero-inflated negative binomial models with 2-stage residual inclusion estimated total and avoidable hospital admissions and ED visits 12 months post-enrollment for adult Medicaid beneficiaries enrolled between August 2017 and December 2018 (n = 19,782)., Results: Compared with low-intensity case management, high-intensity services were associated with a reduction in the incidence rates of inpatient admissions [incidence rate ratio (IRR) = 0.341, 95% CI: 0.106-1.102; P = 0.072], ED visits (IRR = 0.608, 95% CI: 0.188-1.965; P = 0.058), and avoidable ED visits (IRR = 0.579, 95% CI: 0.179-1.872; P = 0.091). No significant association was found between service intensity and the likelihood of an event being an excess zero., Conclusions: High-intensity social needs case management may be more effective than low-intensity service at reducing health care use for individuals with non-zero use, suggesting that intensive case management may be especially helpful in supporting discharge and transitions of care., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to determine whether urine biomarkers of kidney health are associated with subclinical cardiovascular disease among men with and without HIV., Design: A cross-sectional study within the Multicenter AIDS Cohort Study (MACS) among 504 men with and without HIV infection who underwent cardiac computed tomography scans and had urine biomarkers measured within the preceding 2 years., Methods: Our primary predictors were four urine biomarkers of endothelial (albuminuria), proximal tubule dysfunction (alpha-1-microglobulin [A1 M] and injury (kidney injury molecule-1 [KIM-1]) and tubulointerstitial fibrosis (pro-collagen-III N-terminal peptide [PIIINP]). These were evaluated for association with coronary artery calcium (CAC) prevalence, CAC extent, total plaque score, and total segment stenosis using multivariable regression., Results: Of the 504 participants, 384 were men with HIV (MWH) and 120 were men without HIV. In models adjusted for sociodemographic factors, cardiovascular disease risk factors, eGFR, and HIV-related factors, each two-fold higher concentration of albuminuria was associated with a greater extent of CAC (1.35-fold higher, 95% confidence interval 1.11-1.65), and segment stenosis (1.08-fold greater, 95% confidence interval 1.01-1.16). Associations were similar between MWH and men without HIV in stratified analyses. The third quartile of A1 M showed an association with greater CAC extent, total plaque score, and total segment stenosis, compared with the lowest quartile., Conclusion: Worse endothelial and proximal tubule dysfunction, as reflected by higher urine albumin and A1 M, were associated with greater CAC extent and coronary artery stenosis., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: People with HIV (PWH) are at increased risk for premature cardiovascular disease (CVD). Clonal hematopoiesis is a common age-related condition that may be associated with increased CVD risk. The goal of this study was to determine the prevalence of clonal hematopoiesis and its association with chronic inflammation and CVD in PWH., Design: Cross-sectional study utilizing archived specimens and data from 118 men (86 PWH and 32 HIV-uninfected) from the Baltimore-Washington DC center of the Multicenter AIDS Cohort Study (MACS) who had had coronary computed tomography angiography (CTA) and measurement of 34 serologic inflammatory biomarkers., Methods: Clonal hematopoiesis was assessed on peripheral blood mononuclear cells utilizing targeted error-corrected next generation sequencing (NGS) focused on 92 genes frequently mutated in hematologic malignancies. Clinical and laboratory data were obtained from the MACS database., Results: Clonal hematopoiesis with a variant allele frequency (VAF) greater than 1% was significantly more common in PWH [20/86 (23.3%)] than in HIV-uninfected men [2/32 (6.3%)] ( P  = 0.035). PWH with clonal hematopoiesis (VAF > 1%) were more likely to have coronary artery stenosis of at least 50% than those without clonal hematopoiesis [6/20 (30%) vs. 6/64 (9%); P  = 0.021]. Presence of clonal hematopoiesis was not significantly associated with serological inflammatory markers, except for significantly lower serum leptin levels; this was not significant after adjustment for abdominal or thigh subcutaneous fat area., Conclusion: Clonal hematopoiesis was more common in PWH and among PWH was associated with the extent of coronary artery disease. Larger studies are needed to further examine the biological and clinical consequences of clonal hematopoiesis in PWH., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine the longitudinal relationships between abnormal glucose metabolism and physical function in persons with HIV (PWH) and without HIV., Design: Prospective cohort study of men with or at risk for HIV in four United States cities between 2006 and 2018., Methods: Men with or at risk for HIV from the Multicenter AIDS Cohort Study (MACS) had semi-annual assessments of glycemic status, grip strength, and gait speed. We used linear mixed models with random intercept to assess associations between glycemic status and physical function. Glycemic status was categorized as normal, impaired fasting glucose (IFG), controlled diabetes mellitus [hemoglobin A1C (HbA1C) <7.5%], or uncontrolled diabetes mellitus (HbA1C ≥ 7.5%)., Results: Of 2240 men, 52% were PWH. Diabetes mellitus was similar among PWH (7.7%) vs. persons without HIV (6.7%, P = 0.36) at baseline. PWH had slower gait speed (1.17 vs. 1.20 m/s, P < 0.01) but similar grip strength (40.1 vs. 39.8 kg, P = 0.76) compared with persons without HIV at baseline. In multivariate models, gait speed decline was greater with controlled diabetes mellitus [-0.018 m/s (-0.032 to -0.005), P = 0.01] and grip strength decline was greater with controlled [-0.560 kg (-1.096 to -0.024), P = 0.04] and uncontrolled diabetes mellitus [-0.937 kg (-1.684 to -0.190), P = 0.01), regardless of HIV serostatus compared with normoglycemic individuals., Discussion: Abnormal glucose metabolism was associated with declines in gait speed and grip strength regardless of HIV serostatus. These data suggest that improvement in glucose control should be investigated as an intervenable target to prevent progression of physical function limitations among PWH., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Disclosures Dr Leucker reports a research grant from Amgen. Dr Brown has served as a consultant to Merck, ViiV Healthcare, Gilead Sciences, Janssen, and Theratechnologies. The other authors report no conflicts.

Background: Racial-ethnic disparities are pervasive in health care. One mechanism that may underlie disparities is variation in shared decision-making (SDM), which encompasses high-quality clinician-patient communication, including deliberative discussions about treatment options., Objectives: To determine whether SDM has causal effects on outcomes and whether these effects are stronger within racial-ethnic concordant clinician-patient relationships., Research Design: We use instrumental variables to estimate the causal effect of SDM on outcomes., Subjects: A total of 60,584 patients from the 2003-2017 Integrated Public Use Microdata Series Medical Expenditure Panel Survey. Years 2018 and 2019 were excluded due to changes in the Medical Expenditure Panel Survey that omitted essential parts of the SDM index., Measures: Our key variable of interest is the SDM index. Outcomes included total, outpatient, and drug expenditures; physical and mental health; and the utilization of inpatient and emergency services., Results: SDM lowers annual total health expenditures for all racial-ethnic groups, but this effect is only moderated among Black patients seen by Black clinicians, more than doubling in size relative to Whites. A similar SDM moderation effect also occurs for both Black patients seen by Black clinicians and Hispanic patients seen by Hispanic clinicians with regard to annual outpatient expenditures. There was no significant effect of SDM on self-reported physical or mental health., Conclusions: High-quality SDM can reduce health expenditures without negatively impacting overall physical or mental health, supporting a business case for health care organizations and systems to improve racial-ethnic clinician-patient concordance for Black and Hispanic patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Increased integration of physician organizations and hospitals into health systems has not necessarily improved clinical integration or patient outcomes. However, federal regulators have issued favorable opinions for clinically integrated networks (CINs) as a way to pursue coordination between hospitals and physicians. Hospital organizational affiliations, including independent practice associations (IPA), physician-hospital organizations (PHOs), and accountable care organizations (ACOs), may support CIN participation. No empirical evidence, however, exists about factors associated with CIN participation., Methods: Data from the 2019 American Hospital Association survey (n = 4405) were analyzed to quantify hospital CIN participation. Multivariable logistic regression models were estimated to examine whether IPA, PHO, and ACO affiliations were associated with CIN participation, controlling for market factors and hospital characteristics., Results: In 2019, 34.6% of hospitals participated in a CIN. Larger, not-for-profit, and metropolitan hospitals were more likely to participate in CINs. In adjusted analyses, hospitals participating in CINs were more likely to have an IPA (9.5% points, P < 0.001), a PHO (6.1% points, P < 0.001), and ACO (19.3% points, P < 0.001) compared with hospitals not participating in a CIN., Conclusions: Over one-third of hospitals participate in a CIN, despite limited evidence about their effectiveness in delivering value. Results suggest that CIN participation may be a response to integrative norms. Future work should attempt to better define CIN participation and strive to disentangle overlapping organizational participation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Diabetes mellitus is a major comorbidity in people with HIV (PWH). Hyperglycemia below diabetic range defines prediabetes (prediabetes mellitus). We compared the progression from prediabetes mellitus to diabetes mellitus in PWH and people without HIV (PWOH)., Methods: Fasting glucose was measured semiannually in the MACS since 1999. Men with prediabetes mellitus (fasting glucose between 100 and 125 mg/dl, confirmed within a year by fasting glucose in the prediabetes mellitus range or HbA1c between 5.7 and 6.4%) were included. The first visit with prediabetes mellitus was the baseline visit. Incident diabetes mellitus was defined as fasting glucose at least 126 mg/dl, confirmed at a subsequent visit, or self-reported diabetes mellitus, or use of anti-diabetes mellitus medication. We used binomial transition models to compare the progression from prediabetes mellitus to diabetes mellitus by HIV serostatus, adjusted for age, number of previous prediabetes mellitus to diabetes mellitus transitions, ethnicity, BMI, family history of diabetes mellitus, and hepatitis C virus (HCV) infection., Results: Between 1999 and 2019, 1584 men (793 PWH; 791 PWOH) with prediabetes mellitus were included. At baseline, PWH were younger (48 vs. 51 years, P < 0.01), had lower BMI (26 vs. 27), were more frequently nonwhite (47 vs. 30%), and HCV-infected as per last measure (8 vs. 4%) than PWOH (all P < 0.01). Over a median 12-year follow-up, 23% of participants developed diabetes mellitus. In adjusted analyses, the risk for incident diabetes mellitus was 40% (95% CI: 0--80%) higher among PWH than PWOH (P = 0.04)., Conclusion: Among men with prediabetes mellitus, PWH had an increased risk of incident diabetes mellitus adjusted for competing risk factors, warranting the evaluation of diabetes mellitus prevention strategies., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Community health centers (CHCs) pivoted to using telehealth to deliver chronic care during the coronavirus COVID-19 pandemic. While care continuity can improve care quality and patients' experiences, it is unclear whether telehealth supported this relationship., Objective: We examine the association of care continuity with diabetes and hypertension care quality in CHCs before and during COVID-19 and the mediating effect of telehealth., Research Design: This was a cohort study., Participants: Electronic health record data from 166 CHCs with n=20,792 patients with diabetes and/or hypertension with ≥2 encounters/year during 2019 and 2020., Methods: Multivariable logistic regression models estimated the association of care continuity (Modified Modified Continuity Index; MMCI) with telehealth use and care processes. Generalized linear regression models estimated the association of MMCI and intermediate outcomes. Formal mediation analyses assessed whether telehealth mediated the association of MMCI with A1c testing during 2020., Results: MMCI [2019: odds ratio (OR)=1.98, marginal effect=0.69, z=165.50, P<0.001; 2020: OR=1.50, marginal effect=0.63, z=147.73, P<0.001] and telehealth use (2019: OR=1.50, marginal effect=0.85, z=122.87, P<0.001; 2020: OR=10.00, marginal effect=0.90, z=155.57, P<0.001) were associated with higher odds of A1c testing. MMCI was associated with lower systolic (β=-2.90, P<0.001) and diastolic blood pressure (β=-1.44, P<0.001) in 2020, and lower A1c values (2019: β=-0.57, P=0.007; 2020: β=-0.45, P=0.008) in both years. In 2020, telehealth use mediated 38.7% of the relationship between MMCI and A1c testing., Conclusions: Higher care continuity is associated with telehealth use and A1c testing, and lower A1c and blood pressure. Telehealth use mediates the association of care continuity and A1c testing. Care continuity may facilitate telehealth use and resilient performance on process measures., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Hypertension is a critical cause of cardiovascular disease, and women with HIV have a higher prevalence of hypertension than women without HIV. The relationship between hypertension and mortality has not been well characterized in women with treated HIV. Here, we estimate the effect of hypertension on 1-year risk of all-cause mortality among women with HIV on antiretroviral therapy (ART) in the United States., Design: An analysis of multicenter, observational cohort data from the Women's Interagency HIV Study (WIHS) collected between 1995 and 2019., Methods: We included women with HIV who reported ever using ART. We used parametric g-computation to estimate the effect of hypertension (SBP ≥140  mmHg, DBP ≥90 mmHg, or use of hypertensive medication) on all-cause mortality within 1 year of a WIHS visit., Results: Among 2929 unique women, we included 57 034 visits with a median age of 45 (interquartile range: 39, 52) years. Women had hypertension at 34.5% of visits, and 641 deaths occurred within 1 year of a study visit. Comparing women at visits with hypertension to women at visits without hypertension, the standardized 1-year risk ratio for mortality was 1.16 [95% confidence interval (95% CI): 1.01-1.33]. The risk ratios were higher in Hispanic (risk ratio: 1.23, 95% CI: 0.86-1.77) and non-Hispanic black women (risk ratio: 1.19, 95% CI: 1.04-1.37) and lower in non-Hispanic white women (risk ratio: 0.93, 95% CI: 0.58-1.48)., Conclusion: Among women with treated HIV, those with hypertension, compared with those without, had an increased 1-year risk of all-cause mortality., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Feminizing hormonal therapy (FHT) and HIV potentially alter cardiovascular disease (CVD) risk in transgender women (TW)., Methods: TW were enrolled in Los Angeles, California and Houston, Texas and frequency-matched to Multicenter AIDS Cohort Study cisgender men (CM) on age, race, substance use, and abacavir use. Biomarkers of CVD risk and inflammation were assessed via ELISA. Wilcoxon rank sum and Fisher's exact tests compared TW and CM. Multivariable linear regression assessed factors associated with biomarker concentrations., Results: TW (HIV+ n  = 75, HIV- n  = 47) and CM (HIV+ n  = 40, HIV- n  = 40) had mean age 43-45 years; TW/CM were 90%/91% non-Hispanic Black, Hispanic, or Multiracial, 26%/53% obese, and 34%/24% current smokers; 67% of TW were on FHT. Among people with HIV (PWH), TW had higher median extracellular newly-identified receptor for advanced glycation end-products (EN-RAGE), lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), soluble tumor necrosis factor receptor type (sTNFR) I/II, interleukin (IL)-8 and plasminogen activator inhibitor (PAI)-1, but lower soluble CD14, von Willebrand factor (vWF) and endothelin (ET)-1 levels than CM. Findings were similar for participants without HIV (all P  < 0.05). In multivariable analysis, TW had higher EN-RAGE, IL-6, IL-8, P selectin, PAI-1, oxLDL and sTNFRI/II concentrations, and lower vWF, independent of HIV serostatus and current FHT use. Both being a TW and a PWH were associated with lower ET-1., Conclusions: Compared to matched cisgender men, trans women have altered profiles of biomarkers associated with systemic inflammation and CVD. Further work is needed to decipher the contributions of FHT to CVD risk in TW with HIV., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Fat quality and quantity may affect health similarly or differently. Fat quality can be assessed by measuring fat density on CT scan (greater density = smaller, higher quality adipocytes). We assessed the effects of tesamorelin, a growth hormone-releasing hormone analogue that reduces visceral fat (VAT) quantity in some people living with HIV (PWH), on fat density., Design: Participants from two completed, placebo-controlled, randomized trials of tesamorelin for central adiposity treatment in PWH were included if they had either a clinical response to tesamorelin (VAT decrease ≥8%, ≈70% of participants) or were placebo-treated., Methods: CT VAT and subcutaneous fat (SAT) density (Hounsfield Units, HU) were measured by a central blinded reader., Results: Participants (193 responders, 148 placebo) were 87% male and 83% white. Baseline characteristics were similar across arms, including VAT (-91 HU both arms, P = 0.80) and SAT density (-94 HU tesamorelin, -95 HU placebo, P = 0.29). Over 26 weeks, mean (SD) VAT and SAT density increased in tesamorelin-treated participants only [VAT: +6.2 (8.7) HU tesamorelin, +0.3 (4.2) HU placebo, P < 0.0001; SAT: +4.0 (8.7) HU tesamorelin, +0.3 (4.8) HU placebo, P < 0.0001]. The tesamorelin effects persisted after controlling for baseline VAT or SAT HU and area, and VAT [+2.3 HU, 95% confidence interval (4.5-7.3), P = 0.001) or SAT (+3.5 HU, 95% confidence interval (2.3-4.7), P < 0.001] area change., Conclusion: In PWH with central adiposity who experienced VAT quantity reductions on tesamorelin, VAT and SAT density increased independent of changes in fat quantity, suggesting that tesamorelin also improves VAT and SAT quality in this group., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to assess the association of cardiovascular disease (CVD) risk scores and coronary artery plaque (CAP) progression in HIV-infected participants., Methods: We studied men with and without HIV-infection enrolled in the Multicenter AIDS Cohort Study (MACS) CVD study. CAP at baseline and follow-up was assessed with cardiac computed tomography angiography (CCTA). We examined the association between baseline risk scores including pooled cohort equation (PCE), Framingham risk score (FRS), and Data collect of Adverse effects of anti-HIV drugs equation (D:A:D) and CAP progression., Results: We studied 495 men (211 HIV-uninfected, 284 HIV-infected). The adjusted odds ratio (aOR) of total plaque volume (TPV) and noncalcified plaque volume (NCPV) progression in the highest relative to lowest tertile was 9.4 [95% confidence interval (95% CI) 2.4-12.1, P < 0.001)] and 7.7 (95% CI 3.1-19.1, P < 0.001) times greater, respectively, among HIV-uninfected men in the PCE atherosclerotic cardiovascular disease (ASCVD) high vs. low-risk category. Among HIV-infected men, the association for TPV and NCPV progression for the same PCE risk categories, odds ratio (OR) 2.8 (95% CI 1.4-5.8, P < 0.01) and OR 2.4 (95% CI 1.2-4.8, P < 0.05), respectively (P values for interaction by HIV = 0.02 and 0.08, respectively). Similar results were seen for the FRS risk scores. Among HIV-uninfected men, PCE high risk category identified the highest proportion of men with plaque progression in the highest tertile, although in HIV-infected men, high-risk category by D:A:D identified the greatest percentage of men with plaque progression albeit with lower specificity than FRS and PCE., Conclusion: PCE and FRS categories predict CAP progression better in HIV-uninfected than in HIV-infected men. Improved CVD risk scores are needed to identify high-risk HIV-infected men for more aggressive CVD risk prevention strategies., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The aim of this study was to define a smoking cessation 'cascade' among USA women with and without HIV and examine differences by sociodemographic characteristics., Design: An observational cohort study using data from smokers participating in the Women's Interagency HIV Study between 2014 and 2019., Methods: We followed 1165 women smokers with and without HIV from their first study visit in 2014 or 2015 until an attempt to quit smoking within approximately 3 years of follow-up, initial cessation (i.e. no restarting smoking within approximately 6 months of a quit attempt), and sustained cessation (i.e. no restarting smoking within approximately 12 months of a quit attempt). Using the Aalen-Johansen estimator, we estimated the cumulative probability of achieving each step, accounting for the competing risk of death., Results: Forty-five percent of smokers attempted to quit, 27% achieved initial cessation, and 14% achieved sustained cessation with no differences by HIV status. Women with some post-high school education were more likely to achieve each step than those with less education. Outcomes did not differ by race. Thirty-six percent [95% confidence interval (95% CI): 31-42] of uninsured women attempted to quit compared with 47% (95% CI: 44-50) with Medicaid and 49% (95% CI: 41-59) with private insurance., Conclusion: To decrease smoking among USA women with and without HIV, targeted, multistage interventions, and increased insurance coverage are needed to address shortfalls along this cascade., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To investigate HIV-related and age-related differences in hip bone structure in men and women., Design: Cross sectional study of bone structure and HIV serostatus., Methods: We used Quantitative Computed Tomography (QCT) data from the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS) to examine cortical thickness (CT) and cortical (CBMD), trabecular (TBMD), and integral (IBMD) bone mineral density across anatomic quadrants of the femoral neck in older adult MSM and women with (PWH) and without (PWOH) HIV infection. The percentage difference (%diff) in the means for CT and BMD overall and by quadrant between PWH and PWOH were estimated., Results: Among 322 MSM (median age 60 years) with bone measures, distributions were similar between HIV serostatus groups with %diff in the quadrant means ranging from -7 to -1% for CT and from -1 to 4% for BMD, and overall lower hip cortical thickness than expected. In contrast, in 113 women (median age 51 years), PWH had lower CT, IBMD and TBMD consistently across all quadrants, with differences ranging from -10 to -20% for CT, -6 to -11% for IBMD and -3 to -6% for TBMD. Estimates reached statistical significance in superoanterior quadrant for CT and IBMD and inferoposterior for CT., Conclusion: Among women, PWH appear to have a thinner cortex and less dense integral bone compared with PWOH, particularly in the superior quadrants whereas MSM overall had a thinner than expected hip cortex., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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

Abstract: Infections with hepatitis C virus (HCV) represent a substantial national and international public health burden. HCV has been associated with numerous extrahepatic conditions and can lead to metabolic derangements that are associated with atherosclerosis and cardiovascular disease. We investigated whether HCV infection is associated with an increased number of acute coronary syndrome (ACS) events among hospitalized patients in an inner-city tertiary hospital.We performed a matched (age, sex, and race/ethnicity) case-control study on patients at least 18 years old admitted to inpatient medical and cardiac services at the University of Maryland Medical Center from 2015 through 2018. The primary outcome was ACS and the primary exposure was HCV infection. Covariates of interest included: alcohol use, tobacco use, illicit drug use, hypertension, diabetes mellitus, human immunodeficiency virus infection, body mass index, dyslipidemia, and family history of coronary heart disease. Covariates with significant associations with both exposure and outcome in bivariate analyses were included in the multivariable analyses of the final adjusted model.There were 1555 cases and 3110 controls included in the final sample. Almost 2% of cases and 2.4% of controls were HCV infected. In adjusted models, there was no significant association found between experiencing an ACS event in those with HCV infection compared to those without HCV infection (odds ratio 0.71, 95% confidence interval 0.45-1.11).We found no significant association between HCV infection and ACS in our study population. However, given the mixed existing literature, the association between HCV and ACS warrants further investigation in future prospective cohort and/or interventional studies., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) has been associated with excess weight gain in some adults, which may be influenced by genetic factors. We assessed mitochondrial DNA (mtDNA) haplogroups and weight gain following switch to INSTI-based ART., Methods: All AIDS Clinical Trials Group A5001 and A5322 participants with mtDNA genotyping who switched to INSTI were included. mtDNA haplogroups were derived from prior genotyping algorithms. Race/ethnicity-stratified piecewise linear mixed effects models assessed the relationship between mtDNA haplogroup and weight change slope differences before and after switch to INSTI., Results: A total of 291 adults switched to INSTI: 78% male, 50% non-Hispanic White, 28% non-Hispanic Black, and 22% Hispanic. The most common European haplogroups were H [n = 66 (45%)] and UK [32 (22%)]. Non-H European haplogroups had a significant increase in weight slope after the switch. This difference was greatest among non-H clade UK on INSTI-based regimens that included tenofovir alafenamide (TAF) [3.67 (95% confidence interval 1.12, 6.21) kg/year; P = 0.005]. Although small sample size limited analyses among non-Hispanic Black and Hispanic persons, similarly significant weight gain was seen among the most common African haplogroup, L3 [n = 29 (39%); slope difference 4.93 (1.54, 8.32) kg/year, P = 0.005], after switching to TAF-containing INSTI-based ART., Conclusion: Those in European mtDNA haplogroup clade UK and African haplogroup L3 had significantly greater weight gain after switching to INSTI-based ART, especially those receiving TAF. Additional studies in large and diverse populations are needed to clarify the mechanisms and host risk factors for weight gain after switching to INSTI-based ART, with and without TAF., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: People living with HIV (PLWH) have an increased risk of pulmonary vascular disease and pulmonary hypertension. Endothelial cell dysfunction is thought to contribute, but human studies have been limited by the invasive nature of conventional measures of pulmonary artery endothelial function (PAEF). We report here a noninvasive MRI approach to measure nitric oxide mediated PAEF by quantifying changes in pulmonary artery area and blood flow during isometric handgrip exercise (IHE), an endothelial nitric oxide dependent stressor. We used this to test the hypothesis that PLWH have impaired PAEF, even before development of pulmonary hypertension., Design: A prospective cohort study., Methods: We enrolled 25 HIV-positive viral-suppressed individuals on stable antiretroviral therapy without known or suspected pulmonary hypertension and 19 matched seronegative control individuals (HIV-negative). Pulmonary artery area and blood flow changes in response to IHE were measured with noncontrast MRI. Data previously collected during nitric oxide-synthase inhibition were analysed to determine the role of nitric oxide in the pulmonary artery response to IHE., Results: Seronegative individuals exhibited the anticipated PA vasodilatory response to IHE, but this was completely absent in HIV-positive individuals who exhibited an impaired area change (-1.1 ± 1.2 vs. +7.7 ± 2.2%, HIV-positive vs. HIV-negative, mean ± SEM, respectively, P = 0.002) and blood flow response (0.2 ± 2.3 vs. 13.5 ± 4.8%, P = 0.005). The pulmonary artery vasodilatory effect of IHE in healthy individuals was fully blocked by nitric oxide-synthase, demonstrating this pulmonary artery response is predominantly nitric oxide mediated., Conclusion: Using noninvasive MRI methods to quantify PAEF, we observed significantly impaired PAEF in PLWH compared with matched HIV-negative controls. Noninvasive PAEF testing may be useful in evaluating early HIV-related pulmonary vascular disease.

The majority of hanging deaths are relatively straightforward when opining the manner of death, typically determined to be suicide. However, there are rare hanging deaths that require the forensic pathologist to seek additional information. Forensic pathologists commonly consider an accidental manner of death when the hanging death scene includes evidence of solitary sexual activity consistent with autoerotic asphyxia. Here, the authors present a case of an initially apparent suicidal hanging where important death scene details photographed by the medical examiner investigator and history provided by family members during subsequent conversations ultimately helped the forensic pathologist conclude an opinion that the hanging was accidental, likely due to autoerotic activity. The decedent, who hanged himself in the closet of his bedroom, was wearing shorts that were initially believed to be inadvertently torn; however, further investigation revealed his shorts were intentionally modified to expose his genitalia. Additional evidence documented from the death scene photographs and conversations with his mother revealed items and activities consistent with autoerotic behavior. Before opining a manner of death in hanging deaths, forensic pathologists are encouraged to consider details beyond that obtained from the initial death scene investigation and postmortem examination. A thorough medicolegal death investigation should not be viewed as introducing cognitive bias, but rather as necessary information needed to determine the most accurate cause and manner of death.

Objective: Frailty is a critical aging-related syndrome marked by diminished physiologic reserve and heightened vulnerability to stress, predictive of major adverse clinical outcomes in HIV-infected and uninfected adults. Frailty is a dynamic state, yet little data exist on predictors and consequences of frailty transitions., Design/methods: Frailty was assessed semiannually among HIV-infected and uninfected persons with prior injection drug use using the five Fried phenotype domains. An inflammatory index score was constructed from IL-6 and soluble TNF-α receptor-1 data. Markov transition models assessed determinants of frailty transitions. Cox proportional hazards models estimated mortality risk., Results: Among 1353 AIDS Linked to the IntraVenous Experience participants with 9559 frailty transition assessments, 33% were HIV-infected. Younger age, higher education, employment, reduced comorbidity, HIV virologic suppression, elevated CD4 nadir (>500 cells/μl) and absence of a prior AIDS diagnosis were significantly associated with both reduced frailty progression and greater frailty recovery. Each SD decrease in inflammatory index score was associated with decreased frailty progression [odds ratio 0.78; 95% confidence interval (CI), 0.65, 0.92] and increased frailty recovery (odds ratio 1.29; 95% CI, 1.08, 1.53). Being frail at one of two consecutive visits was associated with increased mortality, compared with maintenance of a nonfrail state. Being frail at both of two consecutive visits demonstrated the highest mortality risk (hazard ratio 3.23; 95% CI, 2.1, 4.96)., Conclusion: Sustained, and to a lesser degree, intermittent frail states are associated with increased mortality. HIV virologic suppression with earlier antiretroviral therapy, reduced comorbidity, and reduced inflammation may prevent frailty progression and promote frailty recovery, consequently improving survival for persons aging with HIV and persons with prior injection drug use.

Background: People living with human immunodeficiency virus (HIV+) have greater risk for sudden arrhythmic death than HIV-uninfected (HIV-) individuals. HIV-associated abnormal cardiac repolarization may contribute to this risk. We investigated whether HIV serostatus is associated with ventricular repolarization lability by using the QT variability index (QTVI), defined as a log measure of QT-interval variance indexed to heart rate variance., Methods: We studied 1123 men (589 HIV+ and 534 HIV-) from MACS (Multicenter AIDS Cohort Study), using the ZioXT ambulatory electrocardiography patch. Beat-to-beat analysis of up to 4 full days of electrocardiographic data per participant was performed using an automated algorithm (median analyzed duration [quartile 1-quartile 3]: 78.3 [66.3-83.0] hours/person). QTVI was modeled using linear mixed-effects models adjusted for demographics, cardiac risk factors, and HIV-related and inflammatory biomarkers., Results: Mean (SD) age was 60.1 (11.9) years among HIV- and 54.2 (11.2) years among HIV+ participants ( P <0.001), 83% of whom had undetectable (<20 copies/mL) HIV-1 viral load (VL). In comparison with HIV- men, HIV+ men had higher QTVI (adjusted difference of +0.077 [95% CI, +0.032 to +0.123]). The magnitude of this association depended on the degree of viremia, such that in HIV+ men with undetectable VL, adjusted QTVI was +0.064 (95% CI, +0.017 to +0.111) higher than in HIV- men, whereas, in HIV+ men with detectable VL, adjusted QTVI was higher by +0.150 (95% CI, 0.072-0.228) than in HIV- referents. Analysis of QTVI subcomponents showed that HIV+ men had: (1) lower heart rate variability irrespective of VL status, and (2) higher QT variability if they had detectable, but not with undetectable, VL, in comparison with HIV- men. Higher levels of C-reactive protein, interleukin-6, intercellular adhesion molecule-1, soluble tumor necrosis factor receptor 2, and soluble cluster of differentiation-163 (borderline), were associated with higher QTVI and partially attenuated the association with HIV serostatus., Conclusions: HIV+ men have greater beat-to-beat variability in QT interval (QTVI) than HIV- men, especially in the setting of HIV viremia and heightened inflammation. Among HIV+ men, higher QTVI suggests ventricular repolarization lability, which can increase susceptibility to arrhythmias, whereas lower heart rate variability signals a component of autonomic dysfunction.

We evaluated the impact of hepatic steatosis-insulin resistance (HS-IR) and liver fibrosis (LF) on type 2 diabetes mellitus (DM2) using triglyceride-glucose (TyG) and Fibrosis-4 (FIB-4). The incidence of DM2 was 12.9 [95% confidence interval (CI), 16.9-9.7] and 9.8 (95% CI, 6.9-13.6) per 1000 person-years in HS-IR and LF. The prevalence of HS-IR was significantly lower at 12 and 24 months with TDF + (3TC or FTC) + RPV [hazard ratio (HR) 0.5 [95% CI, 0.3-0.8], P < 0.01 at 12 months; 0.6 [0.4-0.9], P = 0.01 at 24 months]., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

: Heightened systemic inflammation contributes to cardiovascular (CVD) events in people living with HIV (PLWH), although not all PLWH develop CVD, thus suggesting a genetic modifying role. We examined GCH1 polymorphisms, which have been associated with reduced endothelial function in European populations with CVD and increased inflammation, in a racially diverse cohort of US PLWH initiating antiretroviral therapy (ART). GCH1 polymorphisms differed by race and were not associated with flow-mediated dilation or carotid intima-media thickness before or after 48 weeks of ART.

Objective: Obesity is a common, modifiable cardiovascular and cerebrovascular risk factor. Among people with HIV, obesity may contribute to multisystem dysregulation including cognitive impairment. We examined body mass index (BMI) and central obesity (waist circumference [WC]) in association with domain-specific cognitive function and 10-year cognitive decline in men with HIV infection (MWH) vs HIV-uninfected (HIV-) men., Methods: A total of 316 MWH and 656 HIV- Multicenter AIDS Cohort Study participants ≥40 years at baseline, with neuropsychological testing every 2 years and concurrent BMI and WC measurements, were included. MWH were included if taking ≥2 antiretroviral agents and had HIV-1 RNA <400 copies/mL at >80% of visits. Mixed-effects models included all visits from 1996 to 2015, stratified by HIV serostatus, and adjusted for sociodemographic, behavioral, and clinical characteristics. At baseline and follow-up, 8% of MWH and 15% of HIV- men and 41% of MWH and 56% of HIV- men were ≥60 years, respectively., Results: Cross-sectionally, higher BMI was inversely associated with motor function in MWH and HIV- men, and attention/working memory in HIV- men. WC was inversely associated with motor function in MWH and HIV- men. Longitudinal associations indicated an obese BMI was associated with a less steep decline in motor function in MWH whereas in HIV- men, obesity was associated with a greater decline in motor function, learning, and memory. WC, or central obesity, showed similar patterns of associations., Conclusion: Higher adiposity is associated with lower cognition cross-sectionally and greater cognitive decline, particularly in HIV- men. Overweight and obesity may be important predictors of neurologic outcomes and avenues for prevention and intervention., (© 2019 American Academy of Neurology.)

Objective: Whether HIV modifies the relationship of serum lipids with coronary atherosclerosis and coronary plaque subtypes is uncertain. We examined the associations between traditional lipids and coronary atherosclerosis among HIV-infected (HIV+) and HIV-uninfected (HIV-) men., Design: The Multicenter AIDS Cohort Study is an observational cohort with a total of 429 HIV+ and 303 HIV- men who had non-contrast cardiac computed tomography performed to measure coronary artery calcium and coronary computed tomography angiography to measure coronary stenosis, coronary plaque presence, and composition., Methods: We used multivariable adjusted prevalence ratios to examine the relationship between the SD difference in each lipid parameter and coronary atherosclerosis., Results: Total cholesterol (TC)/HDL-cholesterol had the strongest associations with coronary atherosclerosis regardless of HIV status. Overall, lipid parameters were most strongly associated with the presence of mixed plaque, stenosis more than 50%, and coronary artery calcium for both HIV+ and HIV- men. HIV+ men had similar, but weaker associations, between lipid parameters and coronary atherosclerosis compared with HIV- men. The strongest association was between the TC/HDL-cholesterol and stenosis more than 50% for both HIV+ [prevalence ratios 1.25 per SD (95% confidence interval 1.07-1.43)] and HIV- men [prevalence ratios 1.46 per SD (95% confidence interval 1.08-1.85)]., Conclusion: The associations between lipids and coronary atherosclerosis tended to be weaker for HIV+ compared with HIV- men, although TC/HDL had the strongest association for both HIV+ and HIV- men. A weaker association between lipid levels and coronary atherosclerosis for HIV+ men may contribute to the decreased discrimination of cardiovascular disease risk observed in HIV+ individuals.

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

Background and Objective: The risk factors of diabetes mellitus (DM) in people with HIV (PWH) may be dynamic in a life course manner. This study aimed to describe incidence of DM and investigate the trajectory of changes in risk factor associated with DM incidence over around 15 years among a statewide cohort of PWH in South Carolina (SC)., Design: This is a population-based cohort study., Methods: Data were retrieved from the integrated statewide electronic health records between 2006 and 2020 in SC. Separate subgroup analysis was conducted according to the patients' different follow up duration (i.e., 5, 10, and 15 years) to observe the evolving risk factors of DM development, using multivariable logistic regressions., Results: The DM incidence among a total of 9115 PWH was 8.9 per 1000 person-years. In the overall model, being >60 years old, hypertension, and obesity were positively associated with DM while alcohol consumption, years of HIV diagnosis and high percentage days of viral suppression were negatively associated with the outcome. In the subgroup analyses, similar risk factors were observed. The odds of DM increased in a graded fashion with age. Hypertension was positively associated with DM in all groups and retention to care was negatively associated with the outcome in groups 1 and 3., Conclusion: This large-scale population-based study has revealed a relatively lower incidence of DM among PWH than some other US States. The evolving risk factors over time underline the need for maintaining retention to care to prevent the occurrence of DM., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We compared bone mineral density (BMD) changes and their correlates, between men and women participating in two randomized trials of initial [antiretroviral therapy (ART)] regimens, with or without tenofovir disoproxil fumarate (TDF)., Methods: Covariates in linear regression models of 48-week hip and spine %BMD changes, by dual energy X-ray absorptiometry, included baseline and 48-week changes in plasma viral load, CD4 cells, plasma C-terminal telopeptide, procollagen 1 N-terminal propeptide and glomerular filtration rates, and the 48-week area under the curve of fractional excretion of phosphate., Results: Despite overall hip and spine BMD declines of 2.8 and 2.9%, respectively, plasma viral load suppression to less than 50 vs. at least 50 copies/ml was associated 1.0% (P = 0.02) and 0.8% (P = 0.01) less BMD decline. Women had lower baseline spine (P = 0.04; n = 59 women, 418 men) and hip BMD (P = 0.01) in adjusted models, with 1.7% more hip decline on ART than men (P = 0.001). Serum phosphate was positively associated with baseline spine BMD in women (P = 0.03) but not men, and area under the curve of fractional excretion of phosphate was negatively associated with spine BMD changes, particularly in women randomized to TDF regimens (P = 0.03 and 0.054 for interactions by sex, and randomization to TDF vs. non-TDF regimens, respectively; n = 44 women, 326 men). Women also had 0.6% (P = 0.004) more hip BMD decline than men associated with each 100 CD4 cells/μl increase on ART (P = 0.02; n = 49 women, 379 men)., Conclusion: Women randomized to TDF-containing ART had accentuated spine loss associated with phosphaturia, and accentuated hip loss associated with CD4 restoration, regardless of TDF exposure. Viral load suppression reduced bone loss.

Objective: Whether older people living with HIV (PLWH) can achieve similar functional benefits with exercise as their uninfected peers and the ideal intensity of exercise needed for these benefits are not known., Design: Sedentary adults (50-75 years) with or without HIV were recruited for 24 weeks of supervised endurance/resistance exercise. After 12 weeks of moderate-intensity exercise, participants were randomized to continue moderate-intensity or advance to high-intensity exercise for an additional 12 weeks., Methods: Outcomes by serostatus and exercise intensity (moderate, high) were compared using linear and mixed effects regression models and controlled for baseline values or week 12 values., Results: A total of 32 PLWH and 37 controls were enrolled; 27 PLWH (12 moderate/15 high) and 29 controls (15 moderate/14 high) completed 24 weeks. PLWH had significantly poorer physical function across nearly all baseline measures. Both groups had significant improvements in all functional measures. From 0 to 12 weeks, PLWH had significantly greater percentage improvements (mean, 95% confidence interval) than controls on VO2 max [5 (0, 10)%]; from 13 to 24 weeks, PLWH had significantly greater percentage improvements on stair climb [-5 (-10, -1)%], and the time to complete a 400-m walk [-3 (-5, -0)%]; all P less than 0.05. An interaction between exercise intensity and HIV serostatus was significant for measures of strength: PLWH randomized to high-intensity gained significantly more strength than moderate-intensity in bench and leg press [6 (0, 12)% and 10 (2, 17)% greater; both P < 0.05]; controls had similar gains regardless of intensity., Conclusion: Both moderate-intensity and high-intensity exercise resulted in significant improvements in physical function; high-intensity exercise may impart greater strength benefits to PLWH.

Objectives: To determine the relationship between glycemic status and cognitive performance in men living with HIV (MLWH) and without HIV infection., Design: A prospective HIV/AIDS cohort study in four US cities between 1999 and 2016., Methods: Glycemic status was categorized as normal glucose, impaired fasting glucose, controlled diabetes mellitus and uncontrolled diabetes mellitus at each semiannual visit. Cognitive performance was evaluated using nine neuropsychological tests which measure attention, constructional ability, verbal learning, executive functioning, memory and psychomotor speed. Linear mixed models were used to assess the association between glycemic status and cognition., Results: Overall, 900 MLWH and 1149 men without HIV were included. MLWH had significantly more person-visits with impaired fasting glucose (52.1 vs. 47.9%) and controlled diabetes mellitus (58.2 vs. 41.8%) than men without HIV (P < 0.05). Compared with men with normal glucose, men with diabetes mellitus had significantly poorer performance on psychomotor speed, executive function and verbal learning (all P < 0.05). There was no difference in cognition by HIV serostatus. The largest effect was observed in individuals with uncontrolled diabetes mellitus throughout the study period, equivalent to 16.5 and 13.4 years of aging on psychomotor speed and executive function, respectively, the effect of which remained significant after adjusting for HIV-related risk factors. Lower CD4+ nadir was also associated with worse cognitive performance., Conclusion: Abnormalities in glucose metabolism were more common among MLWH than men without HIV and were related to impaired cognitive performance. Metabolic status, along with advanced age and previous immunosuppression, may be important predictors of cognition in the modern antiretroviral therapy era.

Objective: The relationships between frailty and body composition in older adults with HIV infection are poorly understood. We sought to describe associations between frailty and measures of body composition among adult men with HIV and without HIV., Design/methods: Men with and without HIV (age 50-69 years) in the Multicenter AIDS Cohort Study (MACS) Bone Strength Substudy were included if evaluated for frailty (by Fried phenotype) and body composition [BMI, waist circumference, abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue, sarcopenia, and osteopenia/osteoporosis]. All participants with HIV infection were on antiretroviral therapy. Multivariate multinomial logistic regression models were used to determine associations of frailty with body composition., Results: A total of 399 men, including 199 men with HIV and 200 men without HIV, both with median age 60 years, constituted our study population. Frailty prevalence was 16% (men with HIV) vs. 8% (men without HIV). HIV serostatus was associated with a 2.43 times higher odds of frailty (P = 0.01). Higher waist circumference, VAT, sarcopenia, and femoral neck osteoporosis were associated with increased odds of frailty (aOR 4.18, 4.45, 4.15, and 13.6, respectively, and all P < 0.05); BMI and SAT were not. None of these measures presented a differential association with frailty by HIV serostatus (all P > 0.20)., Conclusion: Higher abdominal obesity and sarcopenia were associated with frailty among men with and without HIV. Assessment of these body composition parameters may help detect frailty in the clinical setting.

Objective: Despite effective antiretroviral therapy (HAART) and durable viral suppression, many HIV-infected individuals still do not achieve CD4 cell count (CD4) normalization. Vitamin D has immunoregulatory functions, including inducing the development of T cells and higher levels may improve CD4 rebound., Design: Longitudinal study of men from the Multicenter AIDS Cohort Study who virally suppressed following HAART initiation and had pre-HAART and post-HAART 25(OH)D and 1,25(OH)2D measurements and repeated measures of CD4., Methods: CD4 rebound was modeled using a nonlinear mixed effects model. We estimated the adjusted effect (adjusted for pre-HAART antiretroviral exposure, black race, age and CD4 at HAART initiation) of pre-HAART and post-HAART vitamin D metabolite levels on the rate of CD4 increase and final CD4 plateau., Results: Among the 263 HIV-infected HAART initiators with pre-HAART vitamin D measurements, a 1-SD higher pre-HAART 25(OH)2D level was associated with a 9% faster rate of rise (P = 0.02) but no gain in final CD4 plateau. In contrast, a 1-SD higher 1,25(OH)2D level was associated with a 43-cell lower final CD4 (P = 0.04). Among 560 men with post-HAART measurements, findings were similar to those for pre-HAART 25(OH)2D with 1-SD higher level associated with faster rate of rise but no improvement in final CD4., Conclusion: We found no evidence that higher vitamin D metabolite levels pre-HAART or post-HAART are associated with better CD4 outcomes among HIV-infected HAART initiators. However, the value of pre-HAART 1,25(OH)2D levels as an indicator of immune response dysregulation could be further explored.

Objecive: Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is used to assess bone health in HIV patients. DXA measures the amount of mineral, but not other key aspects of bone strength such as bone microarchitecture or bone quality. Trabecular bone score (TBS) and in-vivo microindentation directly measure trabecular microarchitecture and bone tissue quality, respectively. The aim of this study is to measure bone strength properties using these techniques., Results: Forty naive HIV patients who were going to start antiretroviral therapy (ART), a single pill treatment with elvitegravir/cobicistat, tenofovir disoproxil fumarate (TDF), emtricitavine (FTC) were included. A significant reduction in BMD at spine (-3.25%, P < 0.001) and in femoral neck (-3.82%, P = 0.016) between baseline and 48 weeks of treatment were found. Bone microarchitecture score at the spine, as measured by TBS, also significantly decreased from 1.357 (0.09) to 1.322 (0.09) (-2.5%, P = 0.011) between baseline to 48 weeks of treatment. Microindentation (BMSi) values were significantly higher than at baseline [89.04 (4.2) versus 86.07 (6.1); 3.49%, P < 0.001] after 48 weeks of TDF-based ART treatment, indicating improved bone material properties CONCLUSION:: A significant decrease in BMD and TBS were observed after 1 year of TDF therapy. However, tissue quality significantly improved after 1 year of treatment, suggesting a recovery of bone material properties following the control of the infection despite the significant reduction of BMD. These techniques provide additional and necessary information to DXA about bone health in treated HIV patients, and because of its convenience and feasibility they could be routinely apply to assess bone in clinical practice.

Objectives: In the general population, metabolic health often declines as BMI increases. However, some obese individuals maintain metabolic health. HIV and antiretroviral therapy have been associated with metabolic disturbances. We hypothesized that HIV-infected (HIV) men on suppressive antiretroviral therapy experience less metabolic health than HIV-uninfected (HIV) men across all BMI categories., Design/methods: In a cross-sectional analysis of 1018 HIV and 1092 HIV men enrolled in the multicenter AIDS cohort study, Poisson regression with robust variance determined associations between HIV serostatus and metabolic health prevalence (defined as meeting ≤2 of 5 National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome criteria), adjusting for age, race, BMI category, smoking, and hepatitis C virus infection status., Results: HIV men were younger (54 vs. 59 years) and had lower median BMI (25 vs. 27 kg/m). Nonobese HIV men had lower metabolic health prevalence than HIV men (BMI ≤25 kg/m: 80 vs. 94%, P < 0.001; BMI 25-29 kg/m: 64 vs. 71%, P = 0.05), but metabolic health prevalence among obese men did not differ by HIV serostatus (BMI 30-34 kg/m: 35 vs. 39%, P = 0.48; BMI ≥35 kg/m: 27 vs. 25%, P = 0.79). In the adjusted model, nonobese HIV men were less likely to demonstrate metabolic health than nonobese HIV men. Among HIV men, per year darunavir, zidovudine, and stavudine use were associated with lower metabolic health likelihood., Conclusion: Metabolically healthy obesity prevalence does not differ by HIV serostatus. However, among nonobese men, HIV infection is associated with lower metabolic health prevalence, with associations between lack of metabolic health and darunavir and thymidine analog nucleoside reverse transcriptase inhibitor exposure observed.

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

Objectives: Some studies suggest that bioavailable 25-dihydroxyvitamin D [25-(OH)D] is more accurate than total 25-(OH)D as an assessment of vitamin D (VitD) status in black individuals. We hypothesized that increases in bioavailable 25-(OH)D would correlate better with improvement in bone outcomes among black HIV-infected adults., Design: This is a secondary analysis of AIDS Clinical Trials Group A5280, a randomized, double-blind study of VitD3 and calcium supplementation in HIV-infected participants initiating antiretroviral therapy., Methods: Effect of VitD/calcium on total and calculated bioavailable 25-(OH)D, parathyroid hormone, bone turnover markers, and bone mineral density in black and nonblack participants were evaluated at 48 weeks. Wilcoxon signed-rank tests and Wilcoxon rank sum tests assessed within and between-race differences., Results: Of 165 participants enrolled, 129 (40 black and 89 nonblack) had complete data. At baseline, black participants had lower total 25-(OH)D [median (Q1,Q3) 22.6 (15.8, 26.9) vs. 31.1 (23.1, 38.8) ng/ml, P < 0.001] but higher bioavailable 25-(OH)D [2.9 (1.5, 5.2) vs. 2.0 (1.5, 3.0) ng/ml, P = 0.022] than nonblack participants. After 48 weeks of VitD/calcium supplementation, bioavailable 25-(OH)D increased more in black than nonblack participants, but there were no between-race differences change in bone turnover markers or bone mineral density. The associations between increases in 25-(OH)D levels and change in bone outcomes appeared similar for both total and bioavailable 25-(OH)D., Conclusion: Baseline and change in bioavailable 25-(OH)D were higher among black adults initiating antiretroviral therapy with VitD/calcium; however, associations between 25-(OH)D and bone outcomes appeared similar for total and bioavailable 25-(OH)D. The assessment of total 25-(OH)D may be sufficient for evaluation of VitD status in black HIV-infected individuals., Trial Registration Number: NCT01403051.

Objective: A greater burden of physical function impairment occurs in HIV-infected adults; the impact of antiretroviral therapy (ART) initiation on muscle density (less dense = more fat), a measure of muscle quality, is unknown., Design: AIDS Clinical Trials Group Study A5260s, a cardiometabolic substudy of A5257, randomized HIV-infected, ART-naive adults to ritonavir-boosted atazanavir, darunavir, or raltegravir with tenofovir/emtricitabine backbone. Single-slice abdominal computed tomography scans from baseline and week 96 were reanalyzed for total and lean muscle area and density., Methods: Two-sample t-tests described the differences between baseline and week 96 variables. Linear regression analysis was used to explore the role of a priori identified variables and potential confounders., Results: Participants (n = 235) were mostly men (90%); 31% were Black non-Hispanic; 21% were Hispanic. Over 96 weeks, small but significant increases were seen in oblique/transverse abdominal, rectus, and psoas muscle total area (range 0.21-0.83 cm; P < 0.05) but not the lean muscle component (all P ≥ 0.33). Significant decreases in overall density, consistent with increases in fat, were seen in all muscle groups (range -0.87 to -2.4 HU; P < 0.01); for the lean muscle component, only decreases in oblique/transverse abdominal and rectus reached statistical significance (P < 0.05). In multivariable analyses, Black race was associated with increased muscle density and female sex with decreased density; treatment arm was not associated with changes in mass or density., Conclusion: The ART-associated increase in muscle area, regardless of regimen, is likely a reflection of increased fat within the muscle. The consequences of fatty infiltration of muscle on subsequent muscle function require further investigation.

Objectives: To determine the incidence of fracture among aging HIV-infected (HIV+) and uninfected men (HIV-). To evaluate factors independently associated with fracture risk., Design: Prospective, multicenter cohort study of men with or at risk for HIV., Methods: Outcome measures: all fractures (excluding skull, face and digits) and fragility fractures (vertebral column, femur, wrist and humerus) were collected semiannually in 1221 HIV+ and 1408 HIV- men aged at least 40. Adjusted incident rate ratios (aIRR) with an interaction term for age (40-49, 50-59 and ≥60 years) and HIV serostatus were estimated with Poisson regression models accounting for additional risk factors., Results: Fracture incidence increased with age among both HIV+ and HIV- men. Although there was no significant difference in fracture incidence by HIV serostatus among men aged 40-49 years, the HIV+ men aged 50-59 years had a significantly higher incidence of all fractures [aIRR: 2.06 (1.49, 2.84)] and fragility fractures [aIRR: 2.06 (1.21, 3.50)] compared with HIV- participants of similar age. HIV modified the effect of age on all fractures (P = 0.002) but did not significantly modify the effect for fragility fractures (P = 0.135). Hypertension increased the rate of all fractures by 32% after adjustment for covariates [aIRR: 1.32 (1.04, 1.69)]., Conclusion: Fracture incidence increased with age among HIV+ and HIV- men but was higher among HIV+ men. A significant increase in fracture incidence was found among 50-59-year-old HIV+ men, highlighting the importance of osteoporosis screening for HIV-infected men above the age of 50.

Objective: HIV-positive (HIV+) individuals experience an increased burden of coronary artery disease (CAD) not adequately accounted for by traditional CAD risk factors. Coronary endothelial function (CEF), a barometer of vascular health, is depressed early in atherosclerosis and predict future events but has not been studied in HIV+ individuals. We tested whether CEF is impaired in HIV+ patients without CAD as compared with an HIV-negative (HIV-) population matched for cardiac risk factors., Design/methods: In this observational study, CEF was measured noninvasively by quantifying isometric handgrip exercise-induced changes in coronary vasoreactivity with MRI in 18 participants with HIV but no CAD (HIV+CAD-, based on prior imaging), 36 age-matched and cardiac risk factor-matched healthy participants with neither HIV nor CAD (HIV-CAD-), 41 patients with no HIV but with known CAD (HIV-CAD+), and 17 patients with both HIV and CAD (HIV+CAD+)., Results: CEF was significantly depressed in HIV+CAD- patients as compared with that of risk-factor-matched HIV-CAD- patients (P < 0.0001) and was depressed to the level of that in HIV- participants with established CAD. Mean IL-6 levels were higher in HIV+ participants (P < 0.0001) and inversely related to CEF in the HIV+ patients (P = 0.007)., Conclusion: Marked coronary endothelial dysfunction is present in HIV+ patients without significant CAD and is as severe as that in clinical CAD patients. Furthermore, endothelial dysfunction appears inversely related to the degree of inflammation in HIV+ patients as measured by IL-6. CEF testing in HIV+ patients may be useful for assessing cardiovascular risk and testing new CAD treatment strategies, including those targeting inflammation.

: HIV infection, in many circumstances, can now be managed as a chronic disease due to the marked increase in life expectancy since the introduction of combination antiretroviral therapy (ART). As the patients who first had access to combination ART age into their 50s and 60s, the effects of chronic HIV infection on health have become an important research focus in HIV infection. People living with HIV appear to exhibit an earlier occurrence of some aging-related conditions compared to people without HIV, in part due to higher rates of comorbidities, high-risk behaviors (e.g. smoking, substance use), chronic immune activation, inflammation, and ART-specific factors. Some studies have even suggested an earlier-than-expected appearance of the 'geriatric syndromes,' which are complex medical syndromes of older adults that are associated with morbidity and mortality. The geriatric syndromes include a wide variety of disease processes ranging from incontinence and dementia to impairments in physical function. This review will focus on one geriatric syndrome, sarcopenia, in older HIV-infected populations, and its relation to other aging syndromes, including frailty and falls. The contribution of HIV itself, ART exposure, and specific comorbidities, and the importance of early recognition and prevention of these aging syndromes will be highlighted.

Background: Fees charged for similar imaging tests often vary dramatically within the same market, leading to wide variation in insurer spending and consumer cost-sharing. Reference pricing is an insurance design that offers good coverage to patients up to a defined contribution limit but requires the patients who select high-priced facilities to pay the remainder out of pocket., Objectives: To measure the association between implementation of reference pricing and patient choice of facility, test prices, out-of-pocket spending, and insurer spending for advanced imaging (CT and MRI) procedures., Research Design: Difference-in-differences multivariable analysis of insurance claims data. Study included 4751 employees of a national grocery chain (treatment group) and 23,428 enrollees in the nation's largest private insurance plan (comparison group) that used CT or MRI tests between 2010 and 2013., Measures: Patient choice of facility, price paid per test, patient out-of-pocket cost-sharing, and employer spending., Results: Compared with trends in prices paid by insurance enrollees not subject to reference pricing, and after adjusting for characteristics of tests and patients, implementation of reference pricing was associated with a 12.5% (95% CI, -25.0%, 2.1%) reduction in average price paid per test by the end of the second full year of the program for CT scans and a 10.5% (95% CI, -16.9%, 3.6%) for MRIs. Out-of-pocket cost-sharing by patients declined by $71,508 (13.8%). The savings accruing to employees amounted to 45.5% of total savings from reference pricing, with the remainder accruing to the employer., Conclusions: Implementation of reference pricing led to reductions in payments by both employer and employees.