ß-Blocker Use and Clinical Outcomes in Patients With COPD Following Acute Myocardial Infarction.

Importance: While ß-blockers are associated with decreased mortality in cardiovascular disease (CVD), exacerbation-prone patients with chronic obstructive pulmonary disease (COPD) who received metoprolol in the Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease (BLOCK-COPD) trial experienced increased risk of exacerbations requiring hospitalization. However, the study excluded individuals with established indications for the drug, raising questions about the overall risk and benefit in patients with COPD following acute myocardial infarction (AMI). Objective: To investigate whether ß-blocker prescription at hospital discharge is associated with increased risk of mortality or adverse cardiopulmonary outcomes in patients with COPD and AMI. Design, Setting, and Participants: This prospective, longitudinal cohort study with 6 months of follow-up enrolled patients aged 35 years or older with COPD who underwent cardiac catheterization for AMI at 18 BLOCK-COPD network hospitals in the US from June 2020 through May 2022. Exposure: Prescription for any ß-blocker at hospital discharge. Main Outcomes and Measures: The primary outcome was time to the composite outcome of death or all-cause hospitalization or revascularization. Secondary outcomes included death, hospitalization, or revascularization for CVD events, death or hospitalization for COPD or respiratory events, and treatment for COPD exacerbations. Results: Among 3531 patients who underwent cardiac catheterization for AMI, prevalence of COPD was 17.1% (95% CI, 15.8%-18.4%). Of 579 total patients with COPD and AMI, 502 (86.7%) were prescribed a ß-blocker at discharge. Among the 562 patients with COPD included in the final analysis, median age was 70.0 years (range, 38.0-94.0 years) and 329 (58.5%) were male; 553 of the 579 patients (95.5%) had follow-up information. Among those discharged with ß-blockers, there was no increased risk of the primary end point of all-cause mortality, revascularization, or hospitalization (hazard ratio [HR], 1.01; 95% CI, 0.66-1.54; P = .96) or of cardiovascular events (HR, 1.11; 95% CI, 0.65-1.92; P = .69), COPD-related or respiratory events (HR, 0.75; 95% CI, 0.34-1.66; P = .48), or treatment for COPD exacerbations (rate ratio, 1.01; 95% CI, 0.53-1.91; P = .98). Conclusions and Relevance: In this cohort study, ß-blocker prescription at hospital discharge was not associated with increased risk of adverse outcomes in patients with COPD and AMI. These findings support use of ß-blockers in patients with COPD and recent AMI.

Influence of Impaired Diffusing Capacity and Sleep-disordered Breathing on Nocturnal Hypoxemia and Health Outcomes in Men with and without HIV.

RATIONALE: Nocturnal hypoxemia is common in sleep-disordered breathing (SDB) and is associated with increased morbidity and mortality. Although impaired diffusing capacity of the lungs for carbon monoxide (DLCO) is associated with daytime hypoxemia, its influence on SDB-related nocturnal hypoxemia is not known. OBJECTIVE: To characterize the effects of DLCO impairment on SDB-related nocturnal hypoxemia and associated health outcomes. METHODS: Data from a multi-center cohort of men with and without HIV, with concomitant measures of DLCO and home-based polysomnography (N=544), were analyzed. Multivariable quantile regression models characterized associations between DLCO and several measures of SDB-related hypoxemia (e.g., total sleep time with oxygen saturation [SpO2]<90% [T90]). Structural equation models assessed associations between impaired DLCO and SDB-related hypoxemia measures with prevalent hypertension and type 2 diabetes. RESULTS: DLCO impairment (<80% predicted) was associated with sleep-related hypoxemia. Participants with severe SDB (apnea-hypopnea index≥30 events/hr) and impaired DLCO had a higher T90 (median difference: 15.0%; [95% CI: 10.3,19.7]) and average SDB-related desaturation (median difference: 1.0; [0.5, 1.5]), and lower nadir SpO2 (median difference: -8.2%; [-11.4, -4.9]) and average SpO2 during sleep (median difference: -1.1%; [-2.1, -0.01]), than those with severe SDB and preserved DLCO. A higher T90 was associated with higher adjusted odds of prevalent hypertension (OR 1.39; [1.14,1.70]) and type 2 diabetes (OR 1.25; [1.07,1.46]). CONCLUSIONS: DLCO impairment in severe SDB was associated with sleep-related hypoxemia, prevalent hypertension and type 2 diabetes. Assessment of SDB should be considered in those with impaired DLCO to guide testing and risk-stratification strategies.

The Intersections of COVID-19, HIV, and Race/Ethnicity: Machine Learning Methods to Identify and Model Risk Factors for Severe COVID-19 in a Large U.S. National Dataset.

We investigate risk factors for severe COVID-19 in persons living with HIV (PWH), including among racialized PWH, using the U.S. population-sampled National COVID Cohort Collaborative (N3C) data released from January 1, 2020 to October 10, 2022. We defined severe COVID-19 as hospitalized with invasive mechanical ventilation, extracorporeal membrane oxygenation, discharge to hospice or death. We used machine learning methods to identify highly ranked, uncorrelated factors predicting severe COVID-19, and used multivariable logistic regression models to assess the associations of these variables with severe COVID-19 in several models, including race-stratified models. There were 3 241 627 individuals with incident COVID-19 cases and 81 549 (2.5%) with severe COVID-19, of which 17 445 incident COVID-19 and 1 020 (5.8%) severe cases were among PWH. The top highly ranked factors of severe COVID-19 were age, congestive heart failure (CHF), dementia, renal disease, sodium concentration, smoking status, and sex. Among PWH, age and sodium concentration were important predictors of COVID-19 severity, and the effect of sodium concentration was more pronounced in Hispanics (aOR 4.11 compared to aOR range: 1.47-1.88 for Black, White, and Other non-Hispanics). Dementia, CHF, and renal disease was associated with higher odds of severe COVID-19 among Black, Hispanic, and Other non-Hispanics PWH, respectively. Our findings suggest that the impact of factors, especially clinical comorbidities, predictive of severe COVID-19 among PWH varies by racialized groups, highlighting a need to account for race and comorbidity burden when assessing the risk of PWH developing severe COVID-19.

Association between P-pulmonale and respiratory morbidity in COPD: a secondary analysis of the BLOCK-COPD trial.

RATIONALE: Pulmonary hypertension (PH) in COPD confers increased risk of exacerbations (ECOPD). Electrocardiogram (ECG) indicators of PH are prognostic both in PH and COPD. In the Beta-Blockers for the Prevention of Acute Exacerbations of COPD (BLOCK-COPD) trial, metoprolol increased risk of severe ECOPD through unclear mechanisms. OBJECTIVE: We evaluated whether an ECG indicator of PH, P-pulmonale, would be associated with ECOPD and whether participants with P-pulmonale randomized to metoprolol were at higher risk of ECOPD and worsened respiratory symptoms given the potential detrimental effects of beta-blockers in PH. METHODS: ECGs of 501 participants were analyzed for P-pulmonale (P wave enlargement in lead II). Cox proportional hazards models evaluated for associations between P-pulmonale and time to ECOPD (all and severe) for all participants and by treatment assignment (metoprolol vs. placebo). Linear mixed-effects models evaluated the association between treatment assignment and P-pulmonale on change in symptom scores (measured by CAT and SOBQ). RESULTS: We identified no association between P-pulmonale and risk of any ECOPD or severe ECOPD. However, in individuals with P-pulmonale, metoprolol was associated with increased risk for ECOPD (aHR 2.92, 95% CI: 1.45-5.85). There was no association between metoprolol and ECOPD in individuals without P-pulmonale (aHR 1.01, 95% CI: 0.77-1.31). Individuals with P-pulmonale assigned to metoprolol experienced worsening symptoms (mean increase of 3.95, 95% CI: 1.32-6.58) whereas those assigned to placebo experienced a mean improvement in CAT score of -2.45 (95% CI: -0.30- -4.61). CONCLUSIONS: In individuals with P-pulmonale, metoprolol was associated with increased exacerbation risk and worsened symptoms. These findings may explain the findings observed in BLOCK-COPD.

Associations between GrimAge acceleration and pulmonary function in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Background: The objective of this research was to determine whether pulmonary function is associated with epigenetic aging (GrimAge) and whether GrimAge predicts emphysema. Methods: This prospective study examined 1042 participants enrolled as part of a community-based longitudinal cohort. The cross-sectional associations between pulmonary function and GrimAge, measured at study year (Y) 20 (participant ages 40-45 years), and prospective associations with emphysema at Y25 were examined. Results: At Y20, forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) were negatively associated with GrimAge; for Y0-Y10 cumulative measures, only the FEV1/FVC ratio was associated with GrimAge at Y15 and Y20. Emphysema at Y25 was associated with GrimAge at Y15 and Y20. Conclusion: Pulmonary function was associated with GrimAge during early and mid-life; GrimAge partially mediated the association between pulmonary function and emphysema.

Guideline-discordant inhaler regimens after COPD hospitalization: associations with rurality, drive time to care, and fragmented care - a United States cohort study.

Background: Many patients receive guideline-discordant inhaler regimens after chronic obstructive pulmonary disease (COPD) hospitalization. Geography and fragmented care across multiple providers likely influence prescription of guideline-discordant inhaler regimens, but these have not been comprehensively studied. We assessed patient-level differences in guideline-discordant inhaler regimens by rurality, drive time to pulmonary specialty care, and fragmented care. Methods: Retrospective cohort analysis using national Veterans Health Administration (VA) data among patients who received primary care and prescriptions from the VA. Patients hospitalized for COPD exacerbation between 2017 and 2020 were assessed for guideline-discordant inhaler regimens in the subsequent 3 months. Guideline-discordant inhaler regimens were defined as short-acting inhaler/s only, inhaled corticosteroid (ICS) monotherapy, long-acting beta-agonist (LABA) monotherapy, ICS + LABA, long-acting muscarinic antagonist (LAMA) monotherapy, or LAMA + ICS. Rural residence and drive time to the closest pulmonary specialty care were obtained from geocoded addresses. Fragmented care was defined as hospitalization outside the VA. We used multivariable logistic regression models to assess associations between rurality, drive time, fragmentated care, and guideline-discordant inhaler regimens. Models were adjusted for age, sex, race/ethnicity, Charlson Comorbidity Index, Area Deprivation Index, and region. Findings: Of 33,785 patients, 16,398 (48.6%) received guideline-discordant inhaler regimens 3 months after hospitalization. Rural residents had higher odds of guideline-discordant inhalers regimens compared to their urban counterparts (adjusted odds ratio [aOR] 1.18 [95% CI: 1.12-1.23]). The odds of receiving guideline-discordant inhaler regimens increased with longer drive time to pulmonary specialty care (aOR 1.38 [95% CI: 1.30-1.46] for drive time >90 min compared to <30 min). Fragmented care was also associated with higher odds of guideline-discordant inhaler regimens (aOR 1.56 [95% CI: 1.48-1.63]). Interpretation: Rurality, long drive time to care, and fragmented care were associated with greater prescription of guideline-discordant inhaler regimens after COPD hospitalization. These findings highlight the need to understand challenges in delivering evidence-based care. Funding: NIHNCATS grants KL2TR002492 and UL1TR002494.

HIV-associated lung disease.

Lung disease encompasses acute, infectious processes and chronic, non-infectious processes such as chronic obstructive pulmonary disease, asthma and lung cancer. People living with HIV are at increased risk of both acute and chronic lung diseases. Although the use of effective antiretroviral therapy has diminished the burden of infectious lung disease, people living with HIV experience growing morbidity and mortality from chronic lung diseases. A key risk factor for HIV-associated lung disease is cigarette smoking, which is more prevalent in people living with HIV than in uninfected people. Other risk factors include older age, history of bacterial pneumonia, Pneumocystis pneumonia, pulmonary tuberculosis and immunosuppression. Mechanistic investigations support roles for aberrant innate and adaptive immunity, local and systemic inflammation, oxidative stress, altered lung and gut microbiota, and environmental exposures such as biomass fuel burning in the development of HIV-associated lung disease. Assessment, prevention and treatment strategies are largely extrapolated from data from HIV-uninfected people. Smoking cessation is essential. Data on the long-term consequences of HIV-associated lung disease are limited. Efforts to continue quantifying the effects of HIV infection on the lung, especially in low-income and middle-income countries, are essential to advance our knowledge and optimize respiratory care in people living with HIV.

Bilirubin-associated single nucleotide polymorphism (SNP) and respiratory health outcomes: a mendelian randomization study.

BACKGROUND: Observational studies have shown an association between higher bilirubin levels and improved respiratory health outcomes. Targeting higher bilirubin levels has been proposed as a novel therapeutic strategy in COPD. However, bilirubin levels are influenced by multiple intrinsic and extrinsic factors, and these observational studies are prone to confounding. Genetic analyses are one approach to overcoming residual confounding in observational studies. OBJECTIVES: To test associations between a genetic determinant of bilirubin levels and respiratory health outcomes. METHODS: COPDGene participants underwent genotyping at the baseline visit. We confirmed established associations between homozygosity for rs6742078 and higher bilirubin, and between higher bilirubin and decreased risk of acute respiratory events within this cohort. For our primary analysis, we used negative binomial regression to test associations between homozygosity for rs6742078 and rate of acute respiratory events. RESULTS: 8,727 participants (n = 6,228 non-Hispanic white and 2,499 African American) were included. Higher bilirubin was associated with decreased rate of acute respiratory events [incidence rate ratio (IRR) 0.85, 95% CI 0.75 to 0.96 per SD increase in bilirubin intensity]. We did not find significant associations between homozygosity for rs6742078 and acute respiratory events (IRR 0.94, 95% CI 0.70 to 1.25 for non-Hispanic white and 1.09, 95% CI 0.91 to 1.31 for African American participants). CONCLUSIONS: A genetic determinant of higher bilirubin levels was not associated with better respiratory health outcomes. These results do not support targeting higher bilirubin levels as a therapeutic strategy in COPD.

Pulmonary Function and Quality of Life in Aging Men With and Without HIV from the Multicenter AIDS Cohort Study.

People living with HIV have greater pulmonary function impairments and decreased health-related quality of life (HRQoL) compared to uninfected peers. We examined whether pulmonary impairment was associated with HRQoL or respiratory health status. Using Multicenter AIDS Cohort Study data (2017-2019), associations between outcomes [HRQoL (36-Item Short Form Survey) and respiratory health status (St. George's Respiratory Questionnaire)] with pulmonary impairment [diffusing capacity for carbon monoxide (DLCO) and forced expiratory volume in 1 s (FEV1), defined as <80% predicted for both] were examined. Adjusted analyses utilized linear and zero-inflated beta regression, the latter summarized by odds ratio (OR) and quotient ratios (QRs). We also considered whether the subset of adjustment variables age, HIV serostatus, or smoking modified the relationships examined. Of 1048 men, 55% had HIV, with median age 57 [interquartile range (IQR) = 48, 64] years and 1.2 (IQR = 0, 18.1) smoking pack-years. Impaired DLCO, but not impaired FEV1, was significantly associated with lower physical HRQoL [-2.71 (-4.09, -1.33); -1.46 (-3.45, 0.54), respectively]. Pulmonary impairment was associated with higher odds of any St. George's Respiratory Questionnaire (SGRQ) (total score) limitation [DLCO OR = 1.53 (1.15, 2.04); FEV1 OR = 2.48 (1.16, 5.30)] and was elevated in individuals with more severe SGRQ limitations [DLCO QR = 1.13 (0.94, 1.36); FEV1 QR = 1.27 (0.98, 1.64)]. HIV did not modify any associations examined. Age modified the DLCO and any respiratory limitation (SGRQ symptom score) association for every 10 mL CO/min/mmHg decrease in DLCO [age 30 OR = 1.03 (0.51, 2.08); age 50 OR = 1.85 (1.27, 3.85); and age 70 OR = 3.45 (2.00, 5.88)]. Similarly, age modified the DLCO and any respiratory limitation (SGRQ total score) association. FEV1 associations with SGRQ and HRQoL scores were similar across all ages. Impaired pulmonary function was associated with lower HRQoL and greater respiratory impairments. Future studies can determine if interventions aimed at preserving pulmonary function are effective in improving HRQoL and respiratory health among aging men with and without HIV.

Cardiovascular Autonomic Function and Incident Chronic Obstructive Pulmonary Disease Hospitalizations in Atherosclerosis Risk in Communities.

Rationale: The autonomic nervous system extensively innervates the lungs, but its role in chronic obstructive pulmonary disease (COPD) outcomes has not been well studied. Objective: We assessed relationships between cardiovascular autonomic nervous system measures (heart rate variability [HRV] and orthostatic hypotension [OH]) and incident COPD hospitalization in the multicenter ARIC (Atherosclerosis Risk In Communities) study. Methods: We used Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals between baseline (1987-1989) autonomic function measures (HRV measures from 2-minute electrocardiograms and OH variables) and incident COPD hospitalizations through 2019. Adjusted analyses included demographic data, smoking status, lung function, comorbidities, and physical activity. We also performed analyses stratified by baseline airflow obstruction. Results: Of the 11,625 participants, (mean age, 53.8 yr), 56.5% were female and 26.3% identified as Black. Baseline mean percentage predicted forced expiratory volume in 1 second was 94 ± 17% (standard deviation), and 2,599 participants (22.4%) had airflow obstruction. During a median follow-up time of 26.9 years, there were 2,406 incident COPD hospitalizations. Higher HRV (i.e., better autonomic function) was associated with a lower risk of incident COPD hospitalization. Markers of worse autonomic function (OH and greater orthostatic changes in systolic and diastolic blood pressure) were associated with a higher risk of incident COPD hospitalization (hazard ratio for the presence of OH, 1.5; 95% confidence interval, 1.25-1.92). In stratified analyses, results were more robust in participants without airflow obstruction at baseline. Conclusions: In this large multicenter prospective community cohort, better cardiovascular autonomic function at baseline was associated with a lower risk of subsequent hospitalization for COPD, particularly among participants without evidence of lung disease at baseline.

Elevated Levels of Interleukin-1ß and Interleukin-10 Are Associated With Faster Lung Function Decline in People With Well-Treated Human Immunodeficiency Virus.

BACKGROUND: People with human immunodeficiency virus (PWH) have an increased risk of chronic lung diseases and chronic inflammation. We aimed to investigate if inflammatory markers and monocyte activation are associated with faster lung function decline in PWH. METHODS: We included 655 PWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study. Eligible participants were aged ≥25 years and had 2 spirometries separated by >2 years. Inflammatory markers (interleukin [IL]-1ß, IL-2, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ) were measured at baseline by Luminex, and soluble CD14 and soluble CD163 by enzyme-linked immunosorbent assay. Using linear mixed models, we investigated whether elevated cytokine levels were associated with faster lung function decline. RESULTS: The majority of PWH were males (85.2%) with undetectable viral replication (95.3%). We found a faster decline in forced expiratory volume in 1 second (FEV1) in PWH with elevated IL-1ß and IL-10, with an additional decline of 10.3 mL/year (95% confidence interval [CI], 2.1-18.6; P = .014) and 10.0 mL/year (95% CI, 1.8-18.2; P = .017), respectively. We found no interaction between smoking and IL-1ß or IL-10 on FEV1 decline. CONCLUSIONS: Elevated IL-1ß and IL-10 were independently associated with faster lung function decline in PWH, suggesting that dysregulated systemic inflammation may play a role in the pathogenesis of chronic lung diseases.

Cognitive function and inhaler technique following recovery from exacerbations of COPD.

Cognitive impairment is highly prevalent in COPD outpatients during the post-exacerbation recovery period and is associated with poor inhaler technique https://bit.ly/3XkCvCv.

Pneumoproteins and biomarkers of inflammation and coagulation do not predict rapid lung function decline in people living with HIV.

Chronic obstructive pulmonary disease (COPD) is among the leading causes of death worldwide and HIV is an independent risk factor for the development of COPD. However, the etiology of this increased risk and means to identify persons with HIV (PWH) at highest risk for COPD have remained elusive. Biomarkers may reveal etiologic pathways and allow better COPD risk stratification. We performed a matched case:control study of PWH in the Strategic Timing of Antiretoviral Treatment (START) pulmonary substudy. Cases had rapid lung function decline (> 40 mL/year FEV1 decline) and controls had stable lung function (+ 20 to - 20 mL/year). The analysis was performed in two distinct groups: (1) those who were virally suppressed for at least 6 months and (2) those with untreated HIV (from the START deferred treatment arm). We used linear mixed effects models to test the relationship between case:control status and blood concentrations of pneumoproteins (surfactant protein-D and club cell secretory protein), and biomarkers of inflammation (IL-6 and hsCRP) and coagulation (d-dimer and fibrinogen); concentrations were measured within ± 6 months of first included spirometry. We included an interaction with treatment group (untreated HIV vs viral suppression) to test if associations varied by treatment group. This analysis included 77 matched case:control pairs in the virally suppressed batch, and 42 matched case:control pairs in the untreated HIV batch (n = 238 total) who were followed for a median of 3 years. Median (IQR) CD4 + count was lowest in the controls with untreated HIV at 674 (580, 838). We found no significant associations between case:control status and pneumoprotein or biomarker concentrations in either virally suppressed or untreated PWH. In this cohort of relatively young, recently diagnosed PWH, concentrations of pneumoproteins and biomarkers of inflammation and coagulation were not associated with subsequent rapid lung function decline.Trial registration: NCT00867048 and NCT01797367.

Lung proteome and metabolome endotype in HIV-associated obstructive lung disease.

Purpose: Obstructive lung disease is increasingly common among persons with HIV, both smokers and nonsmokers. We used aptamer proteomics to identify proteins and associated pathways in HIV-associated obstructive lung disease. Methods: Bronchoalveolar lavage fluid (BALF) samples from 26 persons living with HIV with obstructive lung disease were matched to persons living with HIV without obstructive lung disease based on age, smoking status and antiretroviral treatment. 6414 proteins were measured using SomaScan® aptamer-based assay. We used sparse distance-weighted discrimination (sDWD) to test for a difference in protein expression and permutation tests to identify univariate associations between proteins and forced expiratory volume in 1 s % predicted (FEV1 % pred). Significant proteins were entered into a pathway over-representation analysis. We also constructed protein-driven endotypes using K-means clustering and performed over-representation analysis on the proteins that were significantly different between clusters. We compared protein-associated clusters to those obtained from BALF and plasma metabolomics data on the same patient cohort. Results: After filtering, we retained 3872 proteins for further analysis. Based on sDWD, protein expression was able to separate cases and controls. We found 575 proteins that were significantly correlated with FEV1 % pred after multiple comparisons adjustment. We identified two protein-driven endotypes, one of which was associated with poor lung function, and found that insulin and apoptosis pathways were differentially represented. We found similar clusters driven by metabolomics in BALF but not plasma. Conclusion: Protein expression differs in persons living with HIV with and without obstructive lung disease. We were not able to identify specific pathways differentially expressed among patients based on FEV1 % pred; however, we identified a unique protein endotype associated with insulin and apoptotic pathways.

Do sleep disturbances contribute to comorbidities in HIV?

PURPOSE OF REVIEW: To highlight recent publications about sleep disorders and sleep health in adult persons with HIV (PWH), with a focus on how sleep relates to comorbidities in PWH. RECENT FINDINGS: Sleep disorders are more common in PWH than in seronegative controls, especially insomnia, with four different recent studies estimating insomnia prevalence in PWH at 21-35%. Sleep apnea prevalence estimates in PWH have varied widely. Most studies suggest PWH do not have higher sleep apnea prevalence compared with controls, though definitions of sleep apnea may affect these analyses. Comorbidities recently associated with sleep in PWH include myocardial infraction (insomnia), depressive symptoms (insomnia and restless legs syndrome), and pain (insomnia). Cognition associations with sleep were inconsistent and may depend on data collection and analytic methods. Sleep health dimensions are uncommonly reported, but PWH appear to report worse sleep health dimensions and these demonstrated mixed associations with cognition and depressive symptoms in recent studies. SUMMARY: Sleep disorders and poor sleep health are common in PWH and are related to comorbidities. More data from longitudinal studies and clinical trials are needed. Clinical trials of insomnia interventions in PWH are especially warranted.

Faster lung function decline in people living with HIV despite adequate treatment: a longitudinal matched cohort study.

INTRODUCTION: Chronic lung disease is common among people living with HIV (PLWH). We hypothesised that PLWH receiving antiretroviral therapy (ART) have faster lung function decline than matched controls. METHODS: We performed a prospective matched cohort study by including ART-treated PLWH from the Copenhagen Co-morbidity in HIV Infection Study (n=705) and the INSIGHT Strategic Timing of Antiretroviral Treatment Pulmonary Substudy (n=425) and frequency matched population controls from the Copenhagen General Population Study (n=2895) in a 1:3 ratio. Eligible participants were ≥25 years old and had two spirometry tests separated by at least 2 years of follow-up. Forced expiratory volume in 1 s (FEV1) decline (mL/year) was compared between PLWH and controls using a linear mixed model adjusted for age, sex, ethnicity and smoking status. Effect modification by smoking was investigated in subgroup analyses. RESULTS: The majority of PLWH were virally suppressed (96.1%). The adjusted mean annual decline in FEV1 was faster in PLWH than in controls with 36.4 (95% CI 33.7 to 39.1) vs 27.9 (95% CI 26.9 to 28.8) mL/year, yielding a difference of 8.5 (95% CI 5.6 to 11.4) mL/year. The association between HIV and FEV1 decline was modified by smoking, with the largest difference in current smokers (difference: 16.8 (95% CI 10.5 to 23.0) mL/year) and the smallest difference in never-smokers (difference: 5.0 (95% CI 0.7 to 9.3) mL/year). FEV1 decline >40 mL/year was more prevalent in PLWH (adjusted OR: 1.98 (95% CI 1.67 to 2.34)). CONCLUSION: Well-treated PLWH have faster lung function decline than controls and smoking seems to modify this association, suggesting that smoking may lead to more rapid lung function decline in PLWH than in controls.

Current Challenges and Solutions for Clinical Management and Care of People with HIV: Findings from the 12th Annual International HIV and Aging Workshop.

People with HIV on combination antiretroviral therapy (ART) have longer life expectancy and are increasingly experiencing age-related comorbidities. Thus, aging with HIV has become a central issue in clinical care and research, which has been particularly challenging with the intersection of the ongoing coronavirus (COVID)-19 pandemic. Since 2009, the International Workshop on HIV and Aging has served as a multidisciplinary platform to share research findings from cross-disciplinary fields along with community advocates to address critical issues in HIV and aging. In this article, we summarize the key oral presentations from the 12th Annual International Workshop on HIV and Aging, held virtually on September 23rd and 24th, 2021. The topics ranged from basic science research on biological mechanisms of aging to quality of life and delivery of care under the COVID-19 pandemic. This workshop enriched our understanding of HIV and aging under the COVID-19 pandemic, identified challenges and opportunities to combat the impact of COVID-19 on HIV communities, and also provided updated research and future directions of the field to move HIV and aging research forward, with the ultimate goal of successful aging for older people with HIV.

Association between inflammatory biomarker profiles and cardiovascular risk in individuals with and without HIV.

BACKGROUND: People with HIV have an increased risk for cardiovascular morbidity and mortality. Inflammation and immune activation may contribute to this excess risk. METHODS: We assessed thirty-one biomarkers in a subset of POPPY participants and identified three distinct inflammatory profiles: 'gut/immune activation', 'neurovascular', and 'reference' (relatively low levels of inflammation). Ten-year cardiovascular disease (CVD) risk predictions were calculated using the QRISK, Framingham Risk Score (FRS) and the Data Collection on Adverse effects of anti-HIV Drugs (D:A:D) algorithms. The distributions of CVD risk scores across the different inflammatory profiles, stratified by HIV status, were compared using median quantile regression. RESULTS: Of the 312 participants included [70% living with HIV, median (interquartile range; IQR) age 55 (51-60) years; 82% male; 91% white], 36, 130, and 146 were in the 'gut/immune activation', 'neurovascular', and 'reference' cluster, respectively. The median (IQR) QRISK scores were 9.3% (4.5-14.5) and 10.2% (5.5-16.9) for people with and without HV, respectively, with similar scores obtained with the FRS and D:A:D. We observed statistically significant differences between the distributions of scores in the three clusters among people with HV. In particular, median QRISK [5.8% (1.0-10.7) and 3.1% (0.3-5.8)] scores were higher, respectively, for those in the 'gut/immune activation' and 'neurovascular' clusters compared to those in the reference cluster. CONCLUSIONS: People with HIV with increased gut/immune activation have a higher CVD risk compared to those with relatively low inflammation. Our findings highlight that clinically important inflammatory subgroups could be useful to differentiate risk and maximise prediction of CVD among people with HIV.

Lung Function in Women With and Without Human Immunodeficiency Virus.

BACKGROUND: Prior studies have found that human immunodeficiency virus (HIV) infection is associated with impaired lung function and increased risk of chronic lung disease, but few have included large numbers of women. In this study, we investigate whether HIV infection is associated with differences in lung function in women. METHODS: This was a cross-sectional analysis of participants in the Women's Interagency HIV Study, a racially and ethnically diverse multicenter cohort of women with and without HIV. In 2018-2019, participants at 9 clinical sites were invited to perform spirometry. Single-breath diffusing capacity for carbon monoxide (DLCO) was also measured at selected sites. The primary outcomes were the post-bronchodilator forced expiratory volume in 1 second (FEV1) and DLCO. Multivariable regression modeling was used to analyze the association of HIV infection and lung function outcomes after adjustment for confounding exposures. RESULTS: FEV1 measurements from 1489 women (1062 with HIV, 427 without HIV) and DLCO measurements from 671 women (463 with HIV, 208 without HIV) met standards for quality and reproducibility. There was no significant difference in FEV1 between women with and without HIV. Women with HIV had lower DLCO measurements (adjusted difference, -0.73 mL/min/mm Hg; 95% confidence interval, -1.33 to -.14). Among women with HIV, lower nadir CD4 + cell counts and hepatitis C virus infection were associated with lower DLCO measurements. CONCLUSIONS: HIV was associated with impaired respiratory gas exchange in women. Among women with HIV, lower nadir CD4 + cell counts and hepatitis C infection were associated with decreased respiratory gas exchange.