Baltimore oral epidemiology, disease effects, and HIV evaluation study (BEEHIVE) study protocol: a prospective cohort study.

BACKGROUND: As antiretroviral therapy has become widely available and highly effective, HIV has evolved to a manageable, chronic disease. Despite this health advancement, people living with HIV (PLWH) are at an increased risk for age-related non-communicable diseases (NCDs) compared to HIV-uninfected individuals. Similarly, PLWH are at an increased risk for selected oral diseases. PLWH with a history of injecting drugs experience an even greater burden of disease than their counterparts. The overall objective of the Baltimore Oral Epidemiology, Disease Effects, and HIV Evaluation (BEEHIVE) study is to determine the combined effects of HIV infection and NCDs on oral health status. The specific aims of the study are to: (1) determine to what extent HIV status influences access to and utilization of oral health care services; (2) determine to what extent HIV status affects self-reported and clinical oral health status; (3) determine to what extent HIV status influences the progression of periodontitis; and (4) determine to what extent HIV status impacts the periodontitis-associated oral microbiome signature. METHODS: The BEEHIVE study uses a prospective cohort study design to collect data from participants at baseline and at a 24-month follow-up visit. Data are collected through questionnaire assessments, clinical examinations, and evaluation of oral microbiological samples to determine the drivers of oral disease among a high-risk population of PLWH with a history of injection drug use and prevalent comorbid NCDs. The established AIDS Linked to the Intravenous Experience (ALIVE) cohort serves as the source of participants for the BEEHIVE Study. DISCUSSION: Upon completion of the BEEHIVE study, the knowledge gained will be important in informing future clinical and preventive interventions that can be implemented into medical and dental practice to ultimately help eliminate long-standing oral health inequities that PLWH experience.

Coronary artery endothelial function and aging in people with HIV and HIV-negative individuals.

Coronary artery disease (CAD) is a common comorbidity in people with human immunodeficiency virus (HIV) (PWH) and impaired coronary endothelial function (CEF) plays a central role in the pathogenesis of CAD. Age-related impaired CEF among PWH, however, is not well characterized. We investigated the association between CEF and age in males and females with and without HIV using 3-T magnetic resonance imaging (MRI). We measured the changes in coronary cross-sectional area (CSA) and coronary blood flow during isometric handgrip exercise (IHE), an established endothelial-dependent stressor with smaller increases in CSA and coronary blood flow indicative of impaired CEF. We included 106 PWH and 82 individuals without HIV. Differences in demographic and clinical characteristics between PWH and individuals without HIV were explored using Pearson's χ2 test for categorical variables and Welch's t test for continuous variables. Linear regression models were used to examine the association between CEF and age. CEF was significantly lower in PWH as compared with individuals without HIV. Coronary endothelial dysfunction was also present at younger ages in PWH than in the individuals without HIV and there were significant differences in CEF between the PWH and individuals without HIV across age groups. Among the individuals without HIV, the percent changes in CSA were inversely related to age in unadjusted and adjusted models. There was no significant association between CEF and age in PWH. To the best of our knowledge, this is the first study to examine the relationship between age and CEF in PWH, and our results suggest that factors other than age significantly impair CEF in PWH across the life span.NEW & NOTEWORTHY This is the first study to examine the relationship between age and coronary endothelial function (CEF) in people with human immunodeficiency virus (HIV) (PWH). CEF was assessed using magnetic resonance imaging (MRI) in people with and without HIV. Although age and CEF were significantly inversely related in individuals without HIV, there was no association between age and CEF in PWH.

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

BACKGROUND: Infection with human immunodeficiency virus (HIV) is associated with higher risk for myocardial disease despite modern combination antiretroviral therapy (cART). Factors contributing to this excess risk, however, remain poorly characterized. We aimed to assess cross-sectional relationships between elevations of left atrial volume index (LAVI) and myocardial extracellular volume (ECV) fraction that have been reported in persons living with HIV and levels of circulating biomarkers of inflammation, fibrosis, and myocyte stretch among persons living with and without HIV (PLWH, PLWOH). METHODS: Participants from three cohorts of PLWH and PLWOH underwent cardiovascular magnetic resonance imaging for measurement of LAVI and ECV. Levels of circulating proteins (IL-6, sCD14, galectin-3, NT-proBNP, GDF-15, TIMP-2, MMP-2, and hsTnI) were measured using immunoassays. Associations were assessed using logistic and linear regression, adjusting for demographics, substance use, and clinical characteristics. RESULTS: Among 381 participants with and without HIV, median age (IQR) was 55.1 (51.2, 58.4) years, 28% were female, 69% were Black, and 46% were current smokers. Sixty-two percent were PLWH (n = 235), of whom 88% were receiving cART and 72% were virally suppressed. PLWH had higher levels of sCD14 (p = < 0.001), GDF-15 (p = < 0.001), and NT-proBNP (p = 0.03) compared to PLWOH, while levels of other biomarkers did not differ by HIV serostatus, including IL-6 (p = 0.84). Among PLWH, higher sCD14, GDF-15, and NT-proBNP were also associated with lower CD4 + cell count, and higher NT-proBNP was associated with detectable HIV viral load. NT-proBNP was associated with elevated LAVI (OR: 1.79 [95% CI: 1.31, 2.44]; p < 0.001) with no evidence of effect measure modification by HIV serostatus. Other associations between HIV-associated biomarkers and LAVI or ECV were small or imprecise. CONCLUSIONS: Our findings suggest that elevated levels of sCD14, GDF-15, and NT-proBNP among PLWH compared to PLWOH observed in the current cART era may only minimally reflect HIV-associated elevations in LAVI and ECV. Future studies of excess risk of myocardial disease among contemporary cohorts of PLWH should investigate mechanisms other than those connoted by the studied biomarkers.

Frailty and HIV: Moving from Characterization to Intervention.

PURPOSE OF REVIEW: While the characteristics associated with frailty in people with HIV (PWH) have been well described, little is known regarding interventions to slow or reverse frailty. Here we review interventions to prevent or treat frailty in the general population and in people with HIV (PWH). RECENT FINDINGS: Frailty interventions have primarily relied on nonpharmacologic interventions (e.g., exercise and nutrition). Although few have addressed frailty, many of these therapies have shown benefit on components of frailty including gait speed, strength, and low activity among PWH. When nonpharmacologic interventions are insufficient, pharmacologic interventions may be necessary. Many interventions have been tested in preclinical models, but few have been tested or shown benefit among older adults with or without HIV. Ultimately, pharmacologic and nonpharmacologic interventions have the potential to improve vulnerability that underlies frailty in PWH, though clinical data is currently sparse.

COVID-19 Pandemic: Disparate Health Impact on the Hispanic/Latinx Population in the United States.

In December 2019, a novel coronavirus known as SARS-CoV-2, emerged in Wuhan, China, causing the coronavirus disease 2019 we now refer to as COVID-19. The World Health Organization declared COVID-19 a pandemic on 12 March 2020. In the United States, the COVID-19 pandemic has exposed preexisting social and health disparities among several historically vulnerable populations, with stark differences in the proportion of minority individuals diagnosed with and dying from COVID-19. In this article we will describe the emerging disproportionate impact of COVID-19 on the Hispanic/Latinx (henceforth: Hispanic or Latinx) community in the United States, discuss potential antecedents, and consider strategies to address the disparate impact of COVID-19 on this population.

Location Matters: Geographic Disparities and Impact of Coronavirus Disease 2019.

The coronavirus disease 2019 (COVID-19) pandemic in the United States has revealed major disparities in the access to testing and messaging about the pandemic based on the geographic location of individuals, particularly in communities of color, rural areas, and areas of low income. This geographic disparity, in addition to deeply rooted structural inequities, have posed additional challenges to adequately diagnose and provide care for individuals of all ages living in these settings. We describe the impact that COVID-19 has had on geographically disparate populations in the United States and share our recommendations on what might be done to ameliorate the current situation.

Racial Disparity of Coronavirus Disease 2019 in African American Communities.

The coronavirus disease 2019 (COVID-19) pandemic has unveiled unsettling disparities in the outcome of the disease among African Americans. These disparities are not new but are rooted in structural inequities that must be addressed to adequately care for communities of color. We describe the historical context of these structural inequities, their impact on the progression of COVID-19 in the African American (black) community, and suggest a multifaceted approach to addressing these healthcare disparities. (Of note, terminology from survey data cited for this article varied from blacks, African Americans, or both; for consistency, we use African Americans throughout.).

Promoting Inclusion, Diversity, Access, and Equity Through Enhanced Institutional Culture and Climate.

Advancing the health of all members of the global community remains core to the mission of the infectious diseases profession. Training, research, healthcare-delivery, and other infectious diseases-related institutions play a central role in meeting this goal. The promotion of inclusion, diversity, access, and equity (IDA&E) is critical to harnessing the full range of human creativity, innovation, and talent necessary to realizing the education, research, patient care, and service missions that constitute the principal objectives of such institutions. Strong and positive institutional cultures and climates are essential to achieving these IDA&E goals. We discuss opportunity gaps that exist in leveraging institutional culture and climate to optimize IDA&E. We further identify effective strategies to address these gaps and achieve excellence in education, research, patient care, and service in infectious diseases and the broader healthcare and biomedical space. We discuss the importance of both local and global context in conceptualizing IDA&E to best achieve these aims.

Association Between HIV Infection and Mitochondrial DNA Copy Number in Peripheral Blood: A Population-Based, Prospective Cohort Study.

BACKGROUND: Low mitochondrial DNA (mtDNA) copy number (CN) is a predictor of adverse aging outcomes, and its status may be altered in human immunodeficiency virus (HIV)-infected persons. This study evaluated the cross-sectional and longitudinal change of mtDNA CN by HIV markers. METHODS: mtDNA CN was measured in the ALIVE (AIDS Linked to the Intravenous Experience) cohort of persons with a history of injecting drugs. Multivariable linear regression models controlling for demographic characteristics, behavior, and hepatitis C virus (HCV) seropositivity assessed the relationship of mtDNA CN to HIV markers (CD4+ T-cell counts, viral load, antiretroviral therapy [ART] use). Linear mixed models tested the association between HIV markers and age-related mtDNA CN trajectories. RESULTS: Among 741 individuals at baseline, 436 (59%) were infected with HIV. HIV-infected individuals who had lower CD4+ T-cell counts (P = .01), had higher viral loads (P < .01), and were not receiving ART (P < .01) had significantly lower mtDNA CNs than uninfected persons; there was no difference between participants who were uninfected and HIV-infected individuals who had well-controlled HIV levels. In longitudinal follow-up of 507 participants, from age 50 years onward, mtDNA CN declined significantly faster among HIV-infected individuals than among HIV-uninfected persons (-0.03 units of change/year vs 0.006 units of change/year; P = .04), even among infected individuals with well-controlled HIV. CONCLUSION: Before 50 years of age, mtDNA CN is similar between HIV-infected individuals with well-controlled HIV and uninfected persons, but from age 50 onward, mtDNA CN declines significantly faster among all infected individuals than among HIV-uninfected persons.

Reducing injection intensity is associated with decreased risk for invasive bacterial infection among high-frequency injection drug users.

BACKGROUND: Bacterial infection is a major cause of morbidity and mortality for persons who inject drugs (PWID). Injection cessation may help abrogate such infections, but maintaining complete cessation is challenging. Limited data exists on the role of reduced injection intensity on invasive bacterial infection risk. We sought to evaluate decreased risk for bacterial infections following cessation and substantive reduction in the injection intensity. METHODS: Participants were persons in the AIDS Linked to the Intravenous Experience (ALIVE) cohort with initial high-frequency injection drug use (> 1 daily). Pooled logistic regression with generalized estimating equations was used to estimate risk for invasive bacterial infection (pneumonia, endocarditis, or sepsis) among participants achieving complete injection cessation or reduced injection intensity relative to those with sustained high-frequency use. RESULTS: Of 2247 study participants with 12,469 paired study visits, complete injection cessation was achieved at 13.5% and reduced injection intensity at 25.5% of study visits. Adjusting for sociodemographics and HIV status, injection cessation was associated with a 54% reduction of bacterial infection at 3 months (odds ratio [OR] 0.46, 95% CI 0.25-0.84) and a 46% reduction at 6 months (OR 0.54, 95% CI 0.36-0.81). Reduced injection intensity was associated with a 36% reduction of infection at 3 months (OR 0.64, 95% CI 0.43-0.96) and a 26% reduction at 6 months (OR 0.74, 95% CI 0.56-0.98). CONCLUSIONS: Both complete cessation and reduced injection frequency demonstrate substantial benefit in reducing invasive bacterial infection risk among PWID. With high rates of relapse into injection use, targeting sustained reductions in drug use intensity may be a key harm reduction modality for improving clinical outcomes in this population.

Inflammation Strikes Again: Frailty and HIV.

PURPOSE OF REVIEW: As a consequence of antiretroviral therapy, the proportion of older HIV-infected adults is increasing, with a concomitant shift in burden of illness to age-related syndromes and disease. Frailty is an age-related syndrome of increased vulnerability to stress, predictive of major adverse clinical outcomes among HIV-infected and uninfected persons alike. Understanding frailty pathogenesis is critical to developing interventions to improve health outcomes in HIV. Here, we review the current evidence for the relationship between inflammation and frailty in HIV, and the potential for novel, inflammation-targeted interventions. RECENT FINDINGS: Dysregulated inflammation has been consistently associated with frailty in elderly HIV-uninfected persons. Dysregulated inflammation is also central to HIV pathophysiology and several recent studies have demonstrated the important association of inflammation with frailty in HIV. Some evidence suggests that anti-inflammatory therapies may be effective in ameliorating the adverse impact of frailty among aging HIV-infected adults, though further investigation is necessary. Inflammation has been implicated in frailty in HIV infection, and improved understanding of the role that inflammation plays in frailty pathogenesis is key to the development of effective therapies to slow or prevent frailty in the vulnerable HIV-infected population.

Frailty in HIV: Epidemiology, Biology, Measurement, Interventions, and Research Needs.

Frailty is a critical aging-related syndrome marked by diminished physiologic reserve and heightened vulnerability to stressors, predisposing to major adverse clinical outcomes, including hospitalization, institutionalization, disability, and death in the general population of older adults. As the proportion of older adults living with HIV increases in the era of antiretroviral therapy, frailty is increasingly recognized to be of significant clinical and public health relevance to the HIV-infected population. This article reviews current knowledge on the epidemiology and biology of frailty and its potential role as a target for reducing disparities in outcomes in HIV; conceptual frameworks and current approaches to frailty measurement; existing data on frailty interventions; and important areas for future research focus necessary to develop and advance effective strategies to prevent or ameliorate frailty and its marked adverse consequences among people living with HIV.

Changes in Inflammatory Cytokines After Chronic Hepatitis C Treatment Among People Living With HIV.

We aimed to evaluate the effect of hepatitis C virus cure on serum inflammatory markers among people with HIV. Among 127 people with HIV, serum alanine aminotransferase, soluble tumor necrosis factor receptor 1, and inflammatory index score were significantly lower at the 24-week time point in patients who achieved sustained virologic response as compared with those who did not.

Association of inadequate sleep with mortality among persons who inject drugs.

BACKGROUND: Inadequate sleep is associated with all-cause mortality in the general population. Substance use has adverse effects on sleep, and insomnia symptoms are common among people with HIV. Therefore, persons who inject drugs may face a heightened risk of adverse outcomes from inadequate sleep. We evaluated the association of inadequate sleep with mortality among persons who inject drugs in a long-standing community cohort. METHODS: Participants were from the AIDS Linked to the IntraVenous Experience (ALIVE) study, a cohort of persons who inject drugs in Baltimore, Maryland, USA. From 2005-2020, perceived sleep adequacy and duration were assessed semiannually using survey. Mortality data were obtained through linkage to the National Death Index-Plus. Cause of death was independently characterized and validated by three physicians. Hazards of all-cause and cause-specific mortality were evaluated using Cox regression accounting for repeated measurements. RESULTS: A total of 2633 participants were included, with a median age at entry of 45.8years; 32.5% were female, and 75% were Black. After adjustment for demographics, mental health, and comorbidities, inadequate sleep was associated with a 32% greater hazard of all-cause mortality (hazard ratio: 1.32, 95% confidence interval: 1.12-1.55) and a 67% greater hazard of HIV/infectious disease-related deaths (hazard ratio: 1.67, 95% confidence interval: 1.15-2.42). Short (<6 hours) and long (≥8 hours) duration of sleep were both associated with higher hazard of all-cause and chronic disease-related mortality (all p < .05). CONCLUSIONS: Sleep plays a critical role in longevity in persons who inject drugs. Research is needed to determine whether interventions targeting sleep improve health and longevity in persons who inject drugs.

Proteomic Signature of HIV-Associated Subclinical Left Atrial Remodeling and Incident Heart Failure.

Background: People living with HIV (PLWH) are at higher risk of heart failure (HF) and preceding subclinical cardiac abnormalities, including left atrial dilation, compared to people without HIV (PWOH). Hypothesized mechanisms include premature aging linked to chronic immune activation. We leveraged plasma proteomics to identify potential novel contributors to HIV-associated differences in indexed left atrial volume (LAVi) among PLWH and PWOH and externally validated identified proteomic signatures with incident HF among a cohort of older PWOH. Methods: We performed proteomics (Olink Explore 3072) on plasma obtained concurrently with cardiac magnetic resonance imaging among PLWH and PWOH in the United States. Proteins were analyzed individually and as agnostically defined clusters. Cross-sectional associations with HIV and LAVi were estimated using multivariable regression with robust variance. Among an independent general population cohort, we estimated associations between identified signatures and LAVi using linear regression and incident HF using Cox regression. Results: Among 352 participants (age 55±6 years; 25% female), 61% were PLWH (88% on ART; 73% with undetectable HIV RNA) and mean LAVi was 29±9 mL/m 2 . Of 2594 analyzed proteins, 439 were associated with HIV serostatus, independent of demographics, hepatitis C virus infection, renal function, and substance use (FDR<0.05). We identified 73 of these proteins as candidate contributors to the independent association between positive HIV serostatus and higher LAVi, enriched in tumor necrosis factor (TNF) signaling and immune checkpoint proteins regulating T cell, B cell, and NK cell activation. We identified one protein cluster associated with LAVi and HIV regardless of HIV viral suppression status, which comprised 42 proteins enriched in TNF signaling, ephrin signaling, and extracellular matrix (ECM) organization. This protein cluster and 30 of 73 individual proteins were associated with incident HF among 2273 older PWOH (age 68±9 years; 52% female; 8.5±1.4 years of follow-up). Conclusion: Proteomic signatures that may contribute to HIV-associated LA remodeling were enriched in immune checkpoint proteins, cytokine signaling, and ECM organization. These signatures were also associated with incident HF among older PWOH, suggesting specific markers of chronic immune activation, systemic inflammation, and fibrosis may identify shared pathways in HIV and aging that contribute to risk of HF.

Mitochondrial DNA copy number is associated with incident chronic kidney disease and proteinuria in the AIDS linked to the intravenous experience cohort.

We evaluated the prospective association of mitochondrial DNA copy number (mtDNA CN) with markers of kidney function among a cohort of persons who inject drugs (PWID). This is a Prospective cohort study nested in the AIDS linked to the intravenous experience cohort (community-based cohort of PWID in Baltimore, MD). mtDNA CN was measured at two time-points 5 years apart using a real-time polymerase chain reaction. Kidney function (estimated glomerular filtration rate [eGFR], serum creatinine, urine protein) was measured annually. We used linear mixed effects models to evaluate kidney function trajectories (N = 946) and Cox regression models to assess hazard of incident CKD (eGFR < 60 at two consecutive visits, N = 739) and proteinuria (urine protein:creatinine ratio > 200, N = 573) by level of mtDNA CN (Low [lowest quartile], vs high [other three quartiles]. Models were adjusted for demographic and behavioral characteristics, HIV and/or HCV infection, and comorbidity burden. Low mtDNA CN was independently associated with higher hazard of incident CKD (aHR: 2.33, 95% CI 1.42, 3.80) and proteinuria (aHR: 1.42, 95% CI 1.04, 1.96). Participants with low mtDNA CN had greater declines in eGFR and greater increases in serum creatinine over time. Low mtDNA CN is associated with more rapid kidney function decline and risk of incident CKD and proteinuria.

Association Between Left Ventricular Scar and Ventricular Ectopy in People Living With and Without HIV.

BACKGROUND: People living with HIV (PLWH) have greater risk for arrhythmic sudden death and heart failure than people without HIV (PWOH), though risk identifiers remain understudied. Higher ventricular ectopy (VE) burden reflects increased arrhythmic susceptibility and cardiomyopathy risk. OBJECTIVES: The purpose of this study was to test if myocardial scar measured by late gadolinium-enhancement cardiovascular magnetic resonance (LGE-CMR) associates with VE by ambulatory electrocardiographic monitoring among PLWH and PWOH with risk factors for HIV, and if the association differs by HIV. METHODS: Participants from 3 cohorts of PLWH and PWOH underwent electrocardiographic monitoring (median wear time 8.3 days) and CMR. Using multivariable regression, we assessed: 1) associations between scar metrics and VE, adjusting for demographics, HIV serostatus, substance use, cardiovascular risk factors, and left ventricular (LV) function/structure; and 2) effect measure modification by HIV. RESULTS: Of 329 participants (median age 55 years, 30% women, 62% PLWH), 109 had LGE (62% PLWH). Ischemic or major nonischemic pattern LGE was associated with high VE burden (adjusted OR: 2.32, P = 0.004) and more PVCs/day (141% higher, P < 0.001). Among people with LGE, greater scar mass correlated with more PVCs/day (P = 0.028). Associations persisted after adjustment for LV function/structure and when excluding PLWH with HIV viremia and showed no effect measure modification by HIV. CONCLUSIONS: Ischemic or major nonischemic pattern LGE and greater scar mass correlated with higher VE burden, independently of LV structure/function, HIV serostatus, and HIV viremia. The findings highlight specific scar characteristics common to PLWH and PWOH with risk factors for HIV that may portend higher risk for arrhythmias and heart failure.

Mortality by cause of death during year 1 of the COVID-19 pandemic in a cohort of older adults from Baltimore Maryland who have injected drugs.

BACKGROUND: In 2020, the first year of the COVID-19 pandemic, overdose deaths increased. However, no studies have characterized changes in mortality during the pandemic in a well-characterized cohort of people who use drugs in active follow-up at the time of pandemic onset. DESIGN: We compared all-cause and cause-specific mortality in the first year of the pandemic (Mar-Dec 2020) to the five years preceding (Jan 2015-Feb 2020), among participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study: a community-recruited cohort of adults from Baltimore who have injected drugs. 3510 participants contributed 17,498 person-years [py] of follow-up time. Cause and dates of death were ascertained through the National Death Index. Comparisons were made for the full cohort and within subgroups with potentially differential levels of vulnerability. RESULTS: All-cause mortality in 2020 was 39.6 per 1000 py, as compared to 37.2 per 1000 py pre- pandemic (Adjusted Incidence Rate Ratio = 1.09, 95%: confidence interval: 0.84-1.41). Increases were mostly attributable to chronic disease deaths; injury/poisoning deaths did not increase. No pre-post differences were statistically significant. CONCLUSION: In this exploratory analysis of an older cohort of urban-dwelling adults who have injected drugs, mortality changes during the first year of the pandemic differed from national trends and varied across potentially vulnerable subgroups. More research is needed to understand determinants of increased risk of mortality during the pandemic among subgroups of people who use drugs.

Mortality among people who inject drugs: a prospective cohort followed over three decades in Baltimore, MD, USA.

BACKGROUND AND AIMS: During the past decades, people who inject drugs (PWID) have been impacted by the development of combination antiretroviral therapy (cART) to combat HIV/AIDS, the prescription opioid crisis and increased use of lethal synthetic opioids. We measured how these dynamics have impacted mortality among PWID in an urban US city. DESIGN: Prospective cohort study using data from the AIDS Linked to the Intravenous Experience (ALIVE). SETTING: Baltimore, MD, USA from 1988 to 2018. PARTICIPANTS: A total of 5506 adult PWIDs (median age at baseline 37 years). MEASUREMENTS: Mortality was identified by linkage to National Death Index-Plus (NDI-Plus) and categorized into HIV/infectious disease (HIV/ID) deaths, overdose and violence-related (drug-related) deaths and chronic disease deaths. Person-time at risk accrued from baseline and ended at the earliest of death or study period. All-cause and cause-specific mortality were calculated annually. The Fine & Gray method was used to estimate the subdistribution hazards of cause-specific deaths accounting for competing risks. FINDINGS: Among 5506 participants with 84 226 person-years of follow-up, 43.9% were deceased by 2018. Among all deaths, 30.5% were HIV/ID deaths, 24.4% drug-related deaths and 33.3% chronic disease deaths. Age-standardized all-cause mortality increased from 23 to 45 per 1000 person-years from 1988 to 1996, declined from 1996 to 2014, then trended upward to 2018. HIV/ID deaths peaked in 1996 coincident with the availability of cART, then continuously declined. Chronic disease deaths increased continuously as the cohort aged. Drug-related deaths declined until 2011, but increased more than fourfold by 2018. HIV/HCV infection and active injecting were independently associated with HIV/ID and drug-related deaths. Female and black participants had a higher risk of dying from HIV/ID deaths and a lower risk of dying from drug-related deaths than male and non-black participants. CONCLUSIONS: Deaths in Baltimore, MD, USA attributable to HIV/ID appear to have declined following the widespread use of combination antiretroviral therapy. Increases in the rates of drug-related deaths in Baltimore were observed prior to and continue in conjunction with national mortality rates associated with the opiate crisis.

SHBG, Bone Mineral Density, and Physical Function Among Injection Drug Users With and Without HIV and HCV.

CONTEXT: Sex hormone-binding globulin (SHBG) is a glycoprotein that regulates the bioavailability of sex hormones and is higher in people with HIV (PWH) and hepatitis C virus (HCV). SHBG is associated with aging-related diseases, including osteoporosis and frailty in the general population. However, the relationship between SHBG concentration and bone mineral density (BMD) and physical function among PWH and HCV is unclear. OBJECTIVE: This study aimed to evaluate the association between chronic infection with HIV and HCV and SHBG, and to assess the relationship of circulating SHBG concentrations with low BMD, physical function impairment, and frailty. METHODS: A cross-sectional study was conducted of 278 HCV-exposed (HCV antibody positive) adults enrolled with and without HIV and HCV from the AIDS Linked to the IntraVenous Experience cohort study into 4 groups: HCV-/HIV-, HCV-/HIV+, HCV+/HIV-, and HCV+/HIV+. We evaluated the association between SHBG concentrations and grip strength, gait speed, Short Physical Performance Battery score, frailty (Fried Frailty Phenotype), and BMD (lumbar spine, total hip, and femoral neck T-score) by using adjusted multivariable regression stratified by sex. RESULTS: SHBG concentrations were higher in women, in those with HIV RNA greater than 400 copies/mL (P = .02) and HCV RNA greater than 15 IU/mL (P < .001). In adjusted models, higher SHBG concentrations among women were statistically significantly associated with lower grip strength (-0.43 [95% CI, -0.77 to -0.081] kg/10 nmol/L, P < .05), higher odds of frailty (odds ratio, 1.49 [95% CI, 1.07 to 2.08], P < .05), and lower T-scores at the lumbar spine (-0.070 [95% CI, -0.15 to -0.001] SD/10 nmol/L T-score BMD, P < .05). Similar associations were not observed among men. CONCLUSION: Higher SHBG concentrations are associated with the presence of HIV and HCV viremia. Among women, but not men, higher SHBG concentrations were associated with lower grip strength, higher odds of frailty, and lower lumbar spine BMD. The underlying mechanisms of these associations require further investigation.