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In the present study, we aimed to investigate the association between soluble CD40 ligand (sCD40L, a marker of platelet activation), soluble thrombomodulin, and syndecan‐1 (both well‐described markers of endothelial dysfunction) and metabolic syndrome in a large cohort of well‐treated people with HIV (PWH) and to elucidate their association with HIV‐specific variables. We included 862 PWH with undetectable viral replication. Our hypotheses were tested using uni‐ and multivariable logistic regression models a priori adjusted for well‐known confounders. While no association of soluble thrombomodulin and syndecan‐1 with MetS was found, high levels of sCD40L (aOR 1.54 [1.07–2.22]) were associated with excess risk of MetS. Given the previously described association between sCD40L, vascular inflammation and endothelial damage, the results presented in our study may suggest a potential role for sCD40L in the well‐known association between cardiometabolic comorbidity and HIV infection. [ABSTRACT FROM AUTHOR]

Background We aimed to determine the prevalence of coronary artery disease (CAD) in persons with human immunodeficiency virus (HIV; PWH) and investigate whether inflammatory markers, including interleukin 6, IL-1β, and high-sensitivity C-reactive protein (hsCRP), were associated with CAD. Methods From the Copenhagen Comorbidity in HIV Infection (COCOMO) study, we included virologically suppressed PWH who underwent coronary computed tomographic (CT) angiography. Any atherosclerosis was defined as >0% stenosis, and obstructive CAD as ≥50% stenosis. Results Among 669 participants (mean age [standard deviation], 51 [11] years; 89% male), 300 (45%) had atherosclerosis, and 119 (18%) had obstructive CAD. The following risk factors were associated with any atherosclerosis and with obstructive CAD: age, male sex, hypertension, diabetes, smoking, dyslipidemia, time with HIV, and current protease inhibitor use. Interleukin 6 (IL-6) and hsCRP levels >2 mg/L were associated with any atherosclerosis and with obstructive CAD in univariable analyses but not after adjustment for traditional risk factors. IL-1β was not associated with CAD. Conclusions In a large population of PWH without viral replication, almost half had angiographically verified atherosclerosis. High concentrations of IL-6 and hsCRP were associated with CAD in univariable analyses, but adjustment for cardiovascular risk factors attenuated the association, suggesting that inflammation may mediate the association between traditional risk factors and CAD. [ABSTRACT FROM AUTHOR]

Background: Monocytes play an important role in inflammation, and monocytosis and monocyte activation are features of chronic inflammation. We aimed to investigate if HIV status was associated with monocyte count and monocyte activation and to assess the relationship between monocyte count and monocyte activation markers and HIV-related factors.Methods: Persons living with HIV (PLWH) with measured monocyte count and sCD14 and sCD163 were included from the Copenhagen Comorbidity in HIV infection (COCOMO) study and matched 1:5 on sex and age with uninfected controls. In addition, 74 uninfected individuals from COCOMO with measured sCD14 and sCD163 were included. Identical protocols and equipment were used to determine monocyte counts and monocyte activation in PLWH and uninfected controls. Linear regression adjusted for age, sex, smoking and waist-to-hip-ratio was used to analyze the association between possible risk factors and monocyte outcomes.Results: We included 871 PLWH and 4355 uninfected controls. PLWH had - 0.021 [- 0.031 - 0.011] × 109/L) lower monocyte count than uninfected controls, and in adjusted analyses HIV status was independently associated with - 0.035 [- 0.045, - 0.025] × 109/L lower monocyte count. In contrast, PLWH had higher sCD163 and sCD14 concentrations than uninfected controls. After adjustment, HIV-status was associated with higher sCD14 and sCD163 concentrations (588 [325, 851] ng/ml, and 194 [57, 330] ng/ml, respectively).Conclusion: PLWH had lower monocyte counts than controls, but the absolute difference was small, and any clinical impact is likely limited. In contrast, concentrations of monocyte activation markers, previously implicated as drivers of non-AIDS comorbidity, were higher in PLWH than in controls. [ABSTRACT FROM AUTHOR]

Persons living with HIV (PLWH) may have increased incidence of cardiovascular events and longer QTc intervals than uninfected persons. We aimed to investigate the incidence and risk factors of de novo major electrocardiogram (ECG) abnormalities and QTc prolongation in well-treated PLWH. We included virologically suppressed PLWH without major ECG abnormalities, who attended the 2-year follow-up in the Copenhagen comorbidity in HIV infection (COCOMO) study. ECGs were categorized according to Minnesota Code Manual. We defined de novo major ECG abnormalities as new major Minnesota Code Manual abnormalities. Prolonged QTc was defined as QTc > 460 ms in females and QTc > 450 ms in males. Of 667 PLWH without major ECG abnormalities at baseline, 34 (5%) developed de novo major ECG abnormalities after a median of 2.3 years. After adjustment, age (RR: 1.57 [1.08–2.28] per decade older), being underweight (RR: 5.79 [1.70–19.71]), current smoking (RR: 2.34 [1.06–5.16]), diabetes (RR: 3.89 [1.72–8.80]) and protease inhibitor use (RR: 2.45 [1.27–4.74) were associated with higher risk of getting de novo major ECG abnormalities. Of PLWH without prolonged QTc at baseline, only 11 (1.6%) participants developed de novo prolonged QTc. Five percent of well-treated PLWH acquired de novo major ECG abnormalities and protease inhibitor use was associated with more than twice the risk of de novo major ECG abnormalities. De novo prolonged QTc was rare and did not seem to constitute a problem in well-treated PLWH. [ABSTRACT FROM AUTHOR]

Background: People living with HIV have increased risk of depression compared with uninfected controls. The determinants of this association are unclear. Alterations in kynurenine (Kyn) metabolism have been associated with depression in uninfected individuals, but whether they are involved in the development of depression in the context of HIV infection is unknown. Methods: A total of 909 people living with HIV were recruited from the Copenhagen Comorbidity in HIV infection study. Information regarding demographics and depression was obtained from questionnaires. HIV-related variables and use of antidepressant medication were collected from patient records. Logistic regression models before and after adjustment for confounders were used to test our hypotheses. Results: The prevalence of depression was 11%. Among traditional risk factors, only being unmarried was associated with greater odds of depression. Higher levels of quinolinic-to-kynurenic acid ratio (P = 0.018) and higher concentrations of quinolinic acid (P = 0.048) were found in individuals with depression than in those without. After adjusting for confounders, high levels of quinolinic-to-kynurenic acid ratio and high concentrations of quinolinic acid remained associated with depression [adjusted odds ratio 1.61 (1.01; 2.59) and adjusted odds ratio 1.68 (1.02; 2.77), respectively]. Conclusions: The results from this study suggest that alterations in the kynurenine pathway of tryptophan metabolism are associated with the presence of depression in the context of HIV infection. [ABSTRACT FROM AUTHOR]

Background: Human immunodeficiency virus (HIV) infection is associated with an increased risk of chronic pulmonary diseases. We compared cytokine concentrations (interleukin 6 [IL-6], interleukin 1β, 2, 4, 10, and 17A, tumor necrosis factor α, interferon γ, soluble CD14 [sCD14] and soluble CD163 [sCD163]) in people with HIV (PWH) and uninfected controls and investigated whether elevated cytokine concentrations were independently associated with lung function indices in PWH.Methods: We performed spirometry and measured cytokine concentrations by Luminex immunoassays or enzyme-linked immunoassay in 951 PWH and 79 uninfected controls from the Copenhagen Comorbidity in HIV Infection study. Regression analyses were used to explore associations between elevated cytokine concentrations and lung function indices.Results: PWH were predominantly male (84.6%) and 94.2% had undetectable viral replication. In PWH, elevated IL-6 was associated with lower forced expiratory volume in 1 second (-212 mL [95% confidence interval, -308 to -116 mL]), lower forced vital capacity (-208 mL [-322 to -93 mL]), and airflow limitation (aOR, 2.62 [1.58-4.36]) (all P < .001) in models adjusted for age, sex, ethnicity, smoking status, body mass index, and CD4 T-cell nadir. The association between IL-6 and dynamic lung function was modified by smoking (P for interaction = .005).Conclusion: IL-6 levels were elevated and independently associated with low dynamic lung function and airflow limitation in well-treated PWH, suggesting that systemic inflammation may contribute to the pathogenesis of chronic pulmonary diseases. [ABSTRACT FROM AUTHOR]

Background: Pulmonary artery enlargement is a marker of pulmonary hypertension. We aimed to determine the proportion with pulmonary artery enlargement among well-treated persons with human immunodeficiency virus HIV (PWH) and uninfected controls.Methods: PWH with a chest computed tomography were included from the ongoing Copenhagen Comorbidity in HIV Infection (COCOMO) study. Age and sex-matched uninfected controls were recruited from the Copenhagen General Population Study. Pulmonary artery enlargement was defined as a ratio of >1 between the diameter of the main pulmonary artery (at the level of its bifurcation) and the diameter of the ascending aorta.Results: In total, 900 PWH were included, and 44 (5%) had a pulmonary artery-aorta ratio (PA:A) >1. After adjustment for age, sex, and body mass index, obesity (adjusted odds ratio, 4.33; 95% confidence interval, 1.76-10.65; P = .001) and injection drug use (IDU) (4.90; 1.00-18.46; P = .03) were associated with higher odds of having a PA:A >1, and pulmonary indices and smoking status were not. HIV seropositivity was borderline associated with a PA:A >1 (adjusted odds ratio, 1.89; 95% confidence interval, .92-3.85; P = .08).Conclusions: A PA:A >1 was common in PWH. Obesity and IDU were independently associated with this finding and HIV serostatus was borderline associated with it, but HIV-related factors were not. Increased awareness may be appropriate in obese PWH and those with IDU. [ABSTRACT FROM AUTHOR]

Background Increased pericardial adipose tissue is associated with higher risk of cardiovascular disease. We aimed to determine whether human immunodeficiency virus (HIV) status was independently associated with larger pericardial adipose tissue volume and to explore possible HIV-specific risk factors. Methods Persons with HIV (PWH) were recruited from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study and matched 1:1 on age and sex to uninfected controls. Pericardial adipose tissue volume was measured using cardiac computed tomography. Results A total of 587 PWH and 587 controls were included. Median age was 52 years, and 88% were male. Human immunodeficiency virus status was independently associated with 17 mL (95% confidence interval [CI], 10–23; P < .001) larger pericardial adipose tissue volume. Larger pericardial adipose tissue volume was associated with low CD4+ nadir and prior use of stavudine, didanosine, and indinavir. Among PWH without thymidine analogue or didanosine exposure, time since initiating combination antiretroviral treatment (per 5-year use) was associated with l6 mL (95% CI, −6 to −25; P  = .002) lower pericardial adipose tissue volume. Conclusions Human immunodeficiency virus status was independently associated with larger pericardial adipose tissue volume. Severe immunodeficiency, stavudine, didanosine, and indinavir were associated with larger pericardial adipose tissue volume. Persons with HIV with prior exposure to these drugs may constitute a distinct cardiovascular risk population. [ABSTRACT FROM AUTHOR]

Background: Increased pericardial adipose tissue is associated with higher risk of cardiovascular disease. We aimed to determine whether human immunodeficiency virus (HIV) status was independently associated with larger pericardial adipose tissue volume and to explore possible HIV-specific risk factors.Methods: Persons with HIV (PWH) were recruited from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study and matched 1:1 on age and sex to uninfected controls. Pericardial adipose tissue volume was measured using cardiac computed tomography.Results: A total of 587 PWH and 587 controls were included. Median age was 52 years, and 88% were male. Human immunodeficiency virus status was independently associated with 17 mL (95% confidence interval [CI], 10-23; P < .001) larger pericardial adipose tissue volume. Larger pericardial adipose tissue volume was associated with low CD4+ nadir and prior use of stavudine, didanosine, and indinavir. Among PWH without thymidine analogue or didanosine exposure, time since initiating combination antiretroviral treatment (per 5-year use) was associated with l6 mL (95% CI, -6 to -25; P = .002) lower pericardial adipose tissue volume.Conclusions: Human immunodeficiency virus status was independently associated with larger pericardial adipose tissue volume. Severe immunodeficiency, stavudine, didanosine, and indinavir were associated with larger pericardial adipose tissue volume. Persons with HIV with prior exposure to these drugs may constitute a distinct cardiovascular risk population. [ABSTRACT FROM AUTHOR]

Background: Coronary artery calcification (CAC) is commonly assessed with Agatston score (AS). A higher sensitivity and precision for the detection of CAC has been demonstrated with calibrated mass score (cMS). We hypothesized that cMS would detect low-level CAC not detectable with AS in a large asymptomatic background population.Methods: Participants (N = 2985) from the Copenhagen General Population Study were evaluated for CAC using both conventional AS and cMS. The population was grouped according to number of traditional risk factors and heart score was used to assess the risk of event for those with no CAC, those with only cMS > 0 and those with both AS and cMS > 0.Results: In participants with an AS = 0, 11% had cMS > 0. The risk profile of this cMS-only group was between that of the CAC-negative participants and those with AS > 0 and cMS > 0. Overall, 6% of the population belonged to the cMS-only group independent of the number of risk factors.Conclusion: In individuals with AS = 0, a fraction was found to have cMS > 0. Based on traditional risk factors, this group has a higher 10-year risk than individuals with both AS = 0 and cMS = 0; cMS might offer very early cardiovascular risk assessment in asymptomatic individuals.Key Points: • In individuals with AS=0, a fraction has CAC with highly sensitive cMS. • This fraction has a higher 10-year risk of cardiovascular disease. • Regardless of risk factors, 6% has CAC detectable only with cMS. • cMS might offer very early cardiovascular risk assessment in asymptomatic individuals. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Objective: Ankle–brachial index is an excellent tool for diagnosing peripheral artery disease (PAD). We aimed to determine the prevalence and risk factors for PAD in people living with HIV (PLWH) compared with uninfected controls. We hypothesized that prevalence of PAD would be higher among PLWH than among controls independent of traditional cardiovascular disease (CVD) risk factors. Methods: PLWH aged 40 years and older were recruited from the Copenhagen comorbidity in HIV infection (COCOMO) study. Sex- and age-matched uninfected controls were recruited from the Copenhagen General Population Study. We defined PAD as ankle–brachial index ≤0.9 and assessed risk factors for PAD using logistic regression adjusting for age, sex, smoking status, dyslipidemia, diabetes, hypertension, and high-sensitivity C-reactive protein. Results: Among 908 PLWH and 11,106 controls, PAD was detected in 112 [12% confidence interval: (95% 10 to 14)] and 623 [6% (95% 5 to 6)], respectively (P < 0.001), odds ratio = 2.4 (95% 1.9 to 2.9), and adjusted odds ratio = 1.8 (95% 1.3 to 2.3, P < 0.001). Traditional CVD risk factors, but not HIV-related variables, were associated with PAD. The strength of the association between PAD and HIV tended to be higher with older age (P = 0.052, adjusted test for interaction). Conclusions: Prevalence of PAD is higher among PLWH compared with uninfected controls, especially among older persons, and remains so after adjusting for traditional CVD risk factors. Our findings expand the evidence base that PLWH have excess arterial disease to also include PAD. The exact biological mechanisms causing this excess risk remain to be elucidated. Until then, focus on management of modifiable traditional risk factors is important. [ABSTRACT FROM AUTHOR]

Objectives: Posttransplant lymphoproliferative disorder (PTLD) in solid organ transplant recipients has a high mortality and may present early (<2 years) or late (≥2 years) posttransplantation. We investigated the clinical characteristics of early and late PTLD among kidney and liver transplant recipients. Methods: Recipients, transplanted at Rigshospitalet, with PTLD development as adults from January 2010 to August 2020, were included. Clinical characteristics, laboratory parameters, and pathology of early and late PTLD were compared. Results: Thirty‐one PTLD cases were detected where 10 (32%) were early and 21 (68%) were late PTLD. EBV DNA in plasma was detected in 78% versus 28% in early and late PTLD (p =.037). None of the recipients with early PTLD and nine recipients with late PTLD (47%) had Ann Arbor stage IV at the time of their diagnosis (p =.006). Cyclophosphamid–Hydroxyrubicin–Oncovin–Prednisolon was used for treatment in 10 (48%) recipients with late PTLD (p = 0.032) only. There was no difference in mortality between the two groups. Conclusions: Recipients with late PTLD had a lower prevalence of detectable EBV DNA in plasma, were diagnosed with more advanced disease, and were more frequently treated with chemotherapy compared to recipients with early PTLD. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. [ABSTRACT FROM AUTHOR]

Biological aging in people with HIV (PWH) with prolonged successful antiretroviral therapy (ART) is convoluted and poorly defined. Here, we aimed to investigate the transcriptomics age estimator (TAE) in a cohort of 178 PWH on prolonged successful ART with immune reconstitution and viral suppression from the Copenhagen Comorbidity (COCOMO) cohort. We also used 143 clinical, demographical, and lifestyle factors to identify the confounders potentially responsible or associated with age acceleration. Among the PWH, 43% had an accelerated aging process (AAP), and 21% had decelerated aging process (DAP). DAP is linked with older age, European ancestry, and higher use of tenofovir disoproxil/alafenamide fumarate. A directionally class‐based gene set enrichment analysis identified the upregulation of inflammatory pathways (e.g., cytokine and Retinoic acid‐inducible gene I (RIG‐I)‐like receptor signaling pathways) and immune response like T‐cell receptor signaling, antigen processing, and presentation in AAP and the downregulation of metabolic processes like oxidative phosphorylation, pyruvate metabolism. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: People with HIV (PWH) have an increased risk of peripheral artery disease (PAD), but the pathogenesis is unknown. We aimed to determine the associations between markers of endothelial dysfunction and platelet activation and both PAD at baseline and de novo PAD in PWH. Methods: In total, 1012 PWH from the longitudinal Copenhagen Comorbidity in HIV-infection (COCOMO) study and 57 age-matched and sex-matched population controls were included. Plasma samples were collected at baseline and analyzed for soluble thrombomodulin, syndecan-1, and CD40 ligand (sCD40L). The ankle-brachial index was measured at baseline and two-year follow-up in PWH. Logistic and Poisson regression models were used to test associations. Results: PWH had higher concentrations of soluble thrombomodulin (P = 0.03) and syndecan-1 (P < 0.001) and lower concentration of sCD40L (P < 0.001) compared with controls. High concentration of soluble thrombomodulin, but not syndecan-1 or sCD40L, was associated with lower odds of PAD in PWH at baseline after adjustments (adjusted odds ratio: 0.50 [0.28, 0.90], P = 0.02). None of the markers were associated with de novo PAD. Conclusions: PWH had higher concentrations of soluble thrombomodulin and syndecan-1 and lower concentration of sCD40L compared with controls. Soluble thrombomodulin was associated with lower odds of PAD at baseline. Further studies are needed to elucidate the pathogenesis of PAD in people with HIV. [ABSTRACT FROM AUTHOR]

Multiomics technologies improve the biological understanding of health status in people living with HIV on antiretroviral therapy (PWH). Still, a systematic and in-depth characterization of metabolic risk profile during successful long-term treatment is lacking. Here, we used multi-omics (plasma lipidomic, metabolomic, and fecal 16 S microbiome) data-driven stratification and characterization to identify the metabolic at-risk profile within PWH. Through network analysis and similarity network fusion (SNF), we identified three groups of PWH (SNF-1-3): healthy (HC)-like (SNF-1), mild at-risk (SNF-3), and severe at-risk (SNF-2). The PWH in the SNF-2 (45%) had a severe at-risk metabolic profile with increased visceral adipose tissue, BMI, higher incidence of metabolic syndrome (MetS), and increased di- and triglycerides despite having higher CD4+ T-cell counts than the other two clusters. However, the HC-like and the severe at-risk group had a similar metabolic profile differing from HIV-negative controls (HNC), with dysregulation of amino acid metabolism. At the microbiome profile, the HC-like group had a lower α-diversity, a lower proportion of men having sex with men (MSM) and was enriched in Bacteroides. In contrast, in at-risk groups, there was an increase in Prevotella, with a high proportion of MSM, which could potentially lead to higher systemic inflammation and increased cardiometabolic risk profile. The multi-omics integrative analysis also revealed a complex microbial interplay of the microbiome-associated metabolites in PWH. Those severely at-risk clusters may benefit from personalized medicine and lifestyle intervention to improve their dysregulated metabolic traits, aiming to achieve healthier aging. [ABSTRACT FROM AUTHOR]

Background: Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in organ transplant recipients that may be prevented by antibiotic prophylaxis. We aimed to investigate the incidence rate (IR) of PCP and the related hospitalization and mortality rates in liver transplant recipients in an era of routine prophylaxis. Methods: We included all adult liver transplant recipients transplanted at Rigshospitalet between January 1, 2011 and October 1, 2019. Microbiology data were obtained from the Danish Microbiology Database (MiBa), a national database containing all data from all Departments of Clinical Microbiology in Denmark receiving samples from both hospitals and general practices. According to local guidelines, PCP prophylaxis was initiated 1 week posttransplantation and discontinued after 6 months or sooner in patients experiencing side effects. Results: We included 343 liver transplant recipients with 1153 person‐years of follow‐up (PYFU), of which 269 (78%) received PCP prophylaxis during the first 6 months posttransplantation. Seven (2%) recipients were diagnosed with PCP during follow‐up. In the first 6 months posttransplantation and in 269 transplant recipients who received prophylaxis there were zero PCP events while the IR was 32 (95% confidence interval [CI] 2.9–148) per 1000 PYFU in 74 recipient who did not receive prophylaxis. During 7th to 12th month posttransplantation the IR was 20 (95% CI: 5.5–53) per 1000 PYFU. All seven (100%) recipients diagnosed with PCP were hospitalized, however none died. Conclusions: PCP was not detected in liver transplant recipients while on prophylaxis. Though, it worth mentioning that two out of the seven PCP patients received high‐dose prednisolone before the PCP event. All liver transplant recipients with PCP were hospitalized, but none died. Randomized clinical trials to determine the optimal duration of prophylaxis are warranted. [ABSTRACT FROM AUTHOR]

Apolipoprotein E (apoE) plays a crucial role in cholesterol metabolism, and high levels of apoE in plasma are associated with cardiovascular disease and all-cause mortality. We aimed to assess if HIV is independently associated with high plasma apoE and to determine HIV-related risk factors for high plasma apoE. We included 661 people with HIV (PWH) from the Copenhagen Comorbidity in HIV (COCOMO) study with available measurement of plasma apoE. COCOMO participants were frequency matched 1:1 on age and sex with controls from the Copenhagen General Population Study. High plasma apoE was defined as levels above the 90th percentile (66.2 mg/L). The association between HIV and high plasma apoE was assessed using logistic regression models. Among PWH, both linear and logistic regression models were used to determine HIV-specific risk factors for high plasma apoE. Mean age was 52 years and 89 % were male. Median plasma apoE was 49.0 mg/L in PWH and 43.3 mg/L in controls, p < 0.001. HIV was associated with higher plasma apoE after adjusting for potential confounders, including triglycerides (odds ratio 2.14 [95 % CI: 1.39–3.29], p < 0.001). In PWH, higher plasma apoE was associated with a previous AIDS-defining condition in linear models before adjustment for triglycerides and integrase strand transfer inhibitor use in fully adjusted linear models. PWH had higher plasma apoE than controls even after adjusting for triglycerides. Further studies are needed to elucidate the clinical impact of high plasma apoE in PWH. [Display omitted] • People with HIV had higher plasma apoE levels than controls from the general population. • Plasma apoE was consistently higher in people with HIV when stratifying by triglyceride levels. • People with HIV also had higher apoE/apoB ratio compared to controls. • Thus, the association between HIV status and apoE was independent of changes in other lipid parameters. [ABSTRACT FROM AUTHOR]

Background Increased risk of asthma and chronic obstructive pulmonary disease has been reported in people living with human immunodeficiency virus (PLWH). Fraction of exhaled nitric oxide (FeNO) is a marker of eosinophilic airway inflammation. We assessed FeNO levels in PLWH and matched uninfected controls and investigated whether human immunodeficiency virus (HIV) status is independently associated with elevated FeNO. Methods FeNO was quantified by NIOX Vero and pulmonary function was assessed by spirometry in 432 PLWH from the Copenhagen Comorbidity in HIV Infection Study and in 1618 age- and sex-matched uninfected controls from the Copenhagen General Population Study. Elevated FeNO was defined as ≥25 parts per billion. Associations between FeNO and HIV status were adjusted for known potential confounders. Results Mean age of PLWH was 50.7 (standard deviation [SD], 11.1) years and 97.4% received combination antiretroviral therapy. PLWH had higher FeNO than uninfected controls (median, 17.0 [interquartile range {IQR}, 11.0–26.0] vs 13.0 [IQR, 9.0–19.0]; P  < .001). Also, PLWH had a higher prevalence of elevated FeNO than uninfected controls (27.5% vs 12.3%; P  < .001). This association remained after adjusting for age, sex, height, smoking status, use of airway medication, blood eosinophils, and immunoglobulin E (adjusted OR [aOR], 3.56 [95% CI, 2.51–5.04]; P  < .001). Elevated FeNO was associated with self-reported asthma (aOR, 2.65 [95% CI, 1.66–4.24]; P  < .001) but not with airflow limitation (aOR, 1.07 [95% CI,.71–1.62]; P  = .745). Conclusions HIV status was independently associated with elevated FeNO, suggesting increased eosinophilic airway inflammation. The potential impact on chronic lung disease pathogenesis needs further investigation. [ABSTRACT FROM AUTHOR]

Background: Health-care workers are thought to be highly exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to investigate the prevalence of antibodies against SARS-CoV-2 in health-care workers and the proportion of seroconverted health-care workers with previous symptoms of COVID-19.Methods: In this observational cohort study, screening was offered to health-care workers in the Capital Region of Denmark, including medical, nursing, and other students who were associated with hospitals in the region. Screening included point-of-care tests for IgM and IgG antibodies against SARS-CoV-2. Test results and participant characteristics were recorded. Results were compared with findings in blood donors in the Capital Region in the study period.Findings: Between April 15 and April 23, 2020, we screened 29 295 health-care workers, of whom 28 792 (98·28%) provided their test results. We identified 1163 (4·04% [95% CI 3·82-4·27]) seropositive health-care workers. Seroprevalence was higher in health-care workers than in blood donors (142 [3·04%] of 4672; risk ratio [RR] 1·33 [95% CI 1·12-1·58]; p<0·001). Seroprevalence was higher in male health-care workers (331 [5·45%] of 6077) than in female health-care workers (832 [3·66%] of 22 715; RR 1·49 [1·31-1·68]; p<0·001). Frontline health-care workers working in hospitals had a significantly higher seroprevalence (779 [4·55%] of 16 356) than health-care workers in other settings (384 [3·29%] of 11 657; RR 1·38 [1·22-1·56]; p<0·001). Health-care workers working on dedicated COVID-19 wards (95 [7·19%] of 1321) had a significantly higher seroprevalence than other frontline health-care workers working in hospitals (696 [4·35%] of 15 983; RR 1·65 [1·34-2·03]; p<0·001). 622 [53·5%] of 1163 seropositive participants reported symptoms attributable to SARS-CoV-2. Loss of taste or smell was the symptom that was most strongly associated with seropositivity (377 [32·39%] of 1164 participants with this symptom were seropositive vs 786 [2·84%] of 27 628 without this symptom; RR 11·38 [10·22-12·68]). The study is registered at ClinicalTrials.gov, NCT04346186.Interpretation: The prevalence of health-care workers with antibodies against SARS-CoV-2 was low but higher than in blood donors. The risk of SARS-CoV-2 infection in health-care workers was related to exposure to infected patients. More than half of seropositive health-care workers reported symptoms attributable to COVID-19.Funding: Lundbeck Foundation. [ABSTRACT FROM AUTHOR]

Background: Low bone mineral density (BMD) has been described in people living with HIV (PLWH). We examined the prevalence of low BMD measured by quantitative computed tomography (QCT), a method that allows 3-dimensional volumetric density measures at the thoracic spine, in well-treated PLWH and uninfected controls and assessed risk factors for reduced BMD. Methods: Cross-sectional study including 718 PLWH from the Copenhagen Co-Morbidity in HIV infection (COCOMO) study and 718 uninfected controls matched on age and sex from the Copenhagen General Population Study (CGPS). Trabecular BMD was determined by QCT. Results: Median BMD was 144.2 mg/cm³ in PLWH vs. 146.6 mg/cm³ in controls (P = 0.580). HIV status was not associated with BMD in univariable or multivariable linear analyses. However, a higher prevalence of very low BMD (T-score ≤ 22.5) was found in PLWH (17.2% vs. 11.0% in controls, P = 0.003). In unadjusted analysis, HIV was associated with very low BMD (odds ratio 1.68 [95% confidence interval: 1.24-2.27], P = 0.001), but this association was not significant after adjusting for age, sex, smoking, alcohol, body mass index, physical activity, and ethnicity. Previous AIDS-defining disease was associated with lower BMD, but no other associations with HIV-specific variables were identified. Conclusion: Using QCT, we found a higher prevalence of very low BMD in PLWH than in controls. However, HIV status was not independently associated with BMD indicating that traditional risk factors contribute to the difference in prevalence of very low BMD. Focus on improvement of lifestyle factors, especially in PLWH with previous AIDS-defining disease, may prevent very low BMD in PLWH. [ABSTRACT FROM AUTHOR]

Abstract Background The association between low bone mineral density (BMD) and the presence of coronary artery calcium (CAC) as a marker of atherosclerosis is unclear. The aim of this study was to assess the potential relationship between volumetric thoracic bone mineral density and coronary calcification in a large population of men and women. Methods Participants from the Copenhagen General Population Study underwent multidetector computed tomography. Volumetric thoracic BMD and CAC were assessed in the same scan. CAC was measured using calibrated mass score (cMS). cMS was dichotomized as cMS = 0 or cMS > 0. The association between BMD and cMS was analyzed using multiple logistic regression in men, premenopausal and postmenopausal women. The model was adjusted for age, BMI, hypertension, hypercholesterolemia, diabetes, known cardiovascular disease and smoking. Results Of 2548 eligible participants, 1163 men and 1385 women, mean age 61 ± 10 were included in the study. Mean BMD was 138 ± 46 mg/cm3 for men and 151 ± 49 mg/cm3 women. In 696 men (67%) and 537 women (41%) cMS was found to be above zero. For men, a decrease in BMD of 100 mg/cm3 was associated to an odds ratio of 1.49 for cMS > 0 (95% confidence interval: 1.04–2.13, P = 0.03). In postmenopausal women, a decrease in BMD of 100 mg/cm3 was associated to an odds ratio of 1.47 for MS > 0 (95% confidence interval: 1.04–2.08, P = 0.03). For premenopausal women, no significant association was found between BMD and cMS (odds ratio = 0.74, 95% confidence interval: 0.36–1.52, P = 0.4). Conclusion Bone mineral density and coronary calcification are inversely related in both men and postmenopausal women, supporting the hypothesis that a direct relation between bone loss and development of atherosclerosis exists irrespective of gender. Highlights • Bone mineral density and coronary calcification can be measured in a single CT scan. • An inverse relation between bone loss and atherosclerosis exist regardless of gender. • It may only be detected using calibrated mass scoring and not the Agatston score. [ABSTRACT FROM AUTHOR]

Objective: Population studies have shown coronary calcium score to improve risk stratification in subjects suspected for cardiovascular disease. The aim of this work was to assess the validity of multidetector computed tomography (MDCT) for measurement of calibrated mass scores (MS) in a phantom study, and to investigate inter-scanner variability for MS and Agaston score (AS) recorded in a population study on two different high-end MDCT scanners.Materials and Methods: A calcium phantom was scanned by a first (A) and second (B) generation 320-MDCT. MS was measured for each calcium deposit from repeated measurements in each scanner and compared to known physical phantom mass. Random samples of human subjects from the Copenhagen General Population Study were scanned with scanner A (N=254) and scanner B (N=253) where MS and AS distributions of these two groups were compared.Results: The mean total MS of the phantom was 32.9±0.8mg and 33.1±0.9mg (p=0.43) assessed by scanner A and B respectively - the physical calcium mass was 34.0mg. Correlation between measured MS and physical calcium mass was R2=0.99 in both scanners. In the population study the median total MS was 16.8mg (interquartile range (IQR): 3.5-81.1) and 15.8mg (IQR: 3.8-63.4) in scanner A and B (p=0.88). The corresponding median total AS were 92 (IQR: 23-471) and 89 (IQR: 40-384) (p=0.64).Conclusion: Calibrated calcium mass score may be assessed with very high accuracy in a calcium phantom by different generations of 320-MDCT scanners. In population studies, it appears acceptable to pool calcium scores acquired on different 320-MDCT scanners. [ABSTRACT FROM AUTHOR]