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Background Biomarkers that provide insight into drivers of aging are needed for people with human immunodeficiency virus (PWH). The study objective was to determine if epigenetic age acceleration (EAA) markers are associated with physiologic frailty measured by the Veterans Aging Cohort Study (VACS) Index and predict all-cause mortality for PWH. Methods Epigenome-wide DNA methylation was profiled in VACS total white blood cell samples collected during 2005–2007 from 531 PWH to generate 6 established markers of EAA. The association of each EAA marker was tested with VACS Index 2.0. All-cause mortality was assessed over 10 years. For each EAA marker, the hazard ratio per increased year was determined using Cox regression. To evaluate mortality discrimination, C-statistics were derived. Results Participants were mostly men (98.5%) and non-Hispanic Black (84.4%), with a mean age of 52.4 years (standard deviation [SD], 7.8 years). Mean VACS Index score was 59.3 (SD, 16.4) and 136 deaths occurred over a median follow-up of 8.7 years. Grim age acceleration (AA), PhenoAA, HannumAA, and extrinsic epigenetic AA were associated with the VACS Index and mortality. HorvathAA and intrinsic epigenetic AA were not associated with either outcome. GrimAA had the greatest mortality discrimination among EAA markers and predicted mortality independently of the VACS Index. One-year increase in GrimAA was associated with a 1-point increase in VACS Index and a 10% increased hazard for mortality. Conclusions The observed associations between EAA markers with physiologic frailty and mortality support future research to provide mechanistic insight into the accelerated aging process and inform interventions tailored to PWH for promoting increased healthspan.

In this study, we evaluated fracture incidence over a 10-year period among men with and without osteomyelitis from the Veterans Aging Cohort Study. Fracture incidence was significantly higher among those with osteomyelitis at all osteoporotic fracture sites after adjusting for key related risk factors. Future prospective studies are warranted.

BACKGROUND: Age-associated conditions are increasingly common among persons living with human immunodeficiency virus (HIV) (PLWH). A longitudinal investigation of their accrual is needed given their implications on clinical care complexity. We examined trends in the co-occurrence of age-associated conditions among PLWH receiving clinical care, and differences in their prevalence by demographic subgroup. METHODS: This cohort study was nested within the North American AIDS Cohort Collaboration on Research and Design. Participants from HIV outpatient clinics were antiretroviral therapy–exposed PLWH receiving clinical care (ie, ≥1 CD4 count) in the United States during 2000–2009. Multimorbidity was irreversible, defined as having ≥2: hypertension, diabetes mellitus, chronic kidney disease, hypercholesterolemia, end-stage liver disease, or non–AIDS-related cancer. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CIs) comparing demographic subgroups were obtained by Poisson regression with robust error variance, using generalized estimating equations for repeated measures. RESULTS: Among 22969 adults, 79% were male, 36% were black, and the median baseline age was 40 years (interquartile range, 34–46 years). Between 2000 and 2009, multimorbidity prevalence increased from 8.2% to 22.4% (P(trend) < .001). Adjusting for age, this trend was still significant (P < .001). There was no difference by sex, but blacks were less likely than whites to have multimorbidity (aPR, 0.87; 95% CI, .77–.99). Multimorbidity was the highest among heterosexuals, relative to men who have sex with men (aPR, 1.16; 95% CI, 1.01–1.34). Hypertension and hypercholesterolemia most commonly co-occurred. CONCLUSIONS: Multimorbidity prevalence has increased among PLWH. Comorbidity prevention and multisubspecialty management of increasingly complex healthcare needs will be vital to ensuring that they receive needed care.

BACKGROUND:The Patient Protection and Affordable Care Act encourages healthcare systems to track quality-of-care measures; little is known about their impact on mortality rates. The objective of this study was to assess associations between HIV quality of care and mortality rates. METHODS:A longitudinal survival analysis of the Veterans Aging Cohort Study included 3038 human immunodeficiency virus (HIV)-infected patients enrolled between June 2002 and July 2008. The independent variable was receipt of ≥80% of 9 HIV quality indicators (QIs) abstracted from medical records in the 12 months after enrollment. Overall mortality rates through 2014 were assessed from the Veterans Health Administration, Medicare, and Social Security National Death Index records. We assessed associations between receiving ≥80% of HIV QIs and mortality rates using Kaplan-Meier survival analysis and adjusted Cox proportional hazards models. Results were stratified by unhealthy alcohol and illicit drug use. RESULTS:The majority of participants were male (97.5%) and black (66.8%), with a mean (standard deviation) age of 49.0 (8.8) years. Overall, 25.9% reported past-year unhealthy alcohol use and 28.4% reported past-year illicit drug use. During 24 805 person-years of follow-up (mean [standard deviation], 8.2 [3.3] years), those who received ≥80% of QIs experienced lower age-adjusted mortality rates (adjusted hazard ratio, 0.75; 95% confidence interval, .65-.86). Adjustment for disease severity attenuated the association. CONCLUSIONS:Receipt of ≥80% of select HIV QIs is associated with improved survival in a sample of predominantly male, black, HIV-infected patients but was insufficient to overcome adjustment for disease severity. Interventions to ensure high-quality care and address underlying chronic illness may improve survival in HIV-infected patients.

Background. Weight gain after antiretroviral therapy (ART) initiation is common, but its implication for mortality is unknown. We evaluated weight change in the first year after ART initiation and its association with subsequent mortality. Methods. Human immunodeficiency virus-infected patients from the Veterans Aging Cohort Study (VACS) who initiated ART between 2000 and 2008, with weight recorded at baseline and 1 year later, were followed another 5 years for mortality. Baseline body mass index (BMI) was classified as underweight (

Background.It is unclear if the risk of liver disease associated with different levels of alcohol consumption is higher for patients infected with human immunodeficiency virus (HIV) or chronic hepatitis C virus (HCV). We evaluated associations between alcohol use categories and advanced hepatic fibrosis, by HIV and chronic HCV status. Methods.We performed a cross-sectional study among participants in the Veterans Aging Cohort Study who reported alcohol consumption at enrollment (701 HIV/HCV-coinfected; 1410 HIV-monoinfected; 296 HCV-monoinfected; 1158 HIV/HCV-uninfected). Alcohol use category was determined by the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and alcohol-related diagnoses and was classified as nonhazardous drinking, hazardous/binge drinking, or alcohol-related diagnosis. Advanced hepatic fibrosis was defined by FIB-4 index >3.25. Results.Within each HIV/HCV group, the prevalence of advanced hepatic fibrosis increased as alcohol use category increased. For each alcohol use category, advanced hepatic fibrosis was more common among HIV-infected than uninfected (nonhazardous: 6.7% vs 1.4%; hazardous/binge: 9.5% vs 3.0%; alcohol-related diagnosis: 19.0% vs 8.6%; P

Background. Compared to uninfected people, human immunodeficiency virus (HIV)-infected individuals may have an increased risk of acute myocardial infarction (AMI). Currently, HIV-infected people are treated to the same blood pressure (BP) goals (

Background. The Veterans Aging Cohort Study (VACS) Index is associated with all-cause mortality in individuals infected with human immunodeficiency virus (HIV). It is also associated with markers of inflammation and may thus reflect physiologic frailty. This analysis explores the association between physiologic frailty, as assessed by the VACS Index, and fragility fracture. Methods. HIV-infected men from VACS were included. We identified hip, vertebral, and upper arm fractures using ICD-9-CM codes. We used Cox regression models to assess fragility fracture risk factors including the VACS Index, its components (age, hepatitis C status, FIB-4 score, estimated glomerular filtration rate, hemoglobin, HIV RNA, CD4 count), and previously identified risk factors for fragility fractures. Results. We included 40 115 HIV-infected male Veterans. They experienced 588 first fragility fractures over 6.0 ± 3.9 years. The VACS Index score (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.11–1.19), white race (HR, 1.92; 95% CI, 1.63–2.28), body mass index (HR, 0.94; 95% CI, .92–.96), alcohol-related diagnoses (HR, 1.65; 95% CI, 1.26–2.17), cerebrovascular disease (HR, 1.95; 95% CI, 1.14–3.33), proton pump inhibitor use (HR, 1.87; 95% CI, 1.54–2.27), and protease inhibitor use (HR, 1.25; 95% CI, 1.04–1.50) were associated with fracture risk. Components of the VACS Index score most strongly associated with fracture risk were age (HR, 1.40; 95% CI, 1.27–1.54), log HIV RNA (HR, 0.91; 95% CI, .88–.94), and hemoglobin level (HR, 0.82; 95% CI, .78–.86). Conclusions. Frailty, as measured by the VACS Index, is an important predictor of fragility fractures among HIV-infected male Veterans.

Background. Biomarkers of inflammation, altered coagulation, and monocyte activation are associated with mortality and cardiovascular disease (CVD) in the general population and among human immunodeficiency virus (HIV)–infected people. We compared biomarkers for inflammation, altered coagulation, and monocyte activation between HIV-infected and uninfected people in the Veterans Aging Cohort Study (VACS). Methods. Biomarkers of inflammation (interleukin-6 [IL-6]), altered coagulation (d-dimer), and monocyte activation (soluble CD14 [sCD14]) were measured in blood samples from 1525 HIV-infected and 843 uninfected VACS participants. Logistic regression was used to determine the association between HIV infection and prevalence of elevated (>75th percentile) biomarkers, adjusting for confounding comorbidities. Results. HIV-infected veterans had less prevalent CVD, hypertension, diabetes, obesity, hazardous drinking, and renal disease, but more dyslipidemia, hepatitis C, and current smoking than uninfected veterans. Compared to uninfected veterans, HIV-infected veterans with HIV-1 RNA ≥500 copies/mL or CD4 count

BACKGROUND: We examined specific causes of mortality in human immunodeficiency virus type 1 (HIV-1)-infected patients who initiated antiretroviral therapy (ART) in Europe and North America from 1996 through 2006, and we quantified associations of prognostic factors with cause-specific mortality. METHODS: We retrospectively classified all deaths among 39,272 patients enrolled in 13 HIV-1 cohorts (154,667 person years of follow-up) into the categories specified in the Cause of Death (CoDe) project protocol. RESULTS: In 1597 (85%) of 1876 deaths, a definitive cause of death could be assigned. Among these, 792 deaths (49.5%) were AIDS related, followed by non-AIDS malignancies (189; 11.8%), non-AIDS infections (131; 8.2%), violence- and/or drug-related causes (124; 7.7%), liver disease (113; 7.0%), and cardiovascular disease (103; 6.5%). Rates of AIDS-related death (hazard ratio [HR] per 100 cell decrease, 1.43; 95% confidence interval [CI], 1.34-1.53) and death from renal failure (HR, 1.73; 95% CI, 1.18-2.55) were strongly inversely related to CD4 count at initiation of ART, whereas rates of death attributable to AIDS (HR for viral load >5 vs 5 log copies/mL, 1.31; 95% CI, 1.12-1.53), infection (HR, 1.85; 95% CI, 1.25-2.73), cardiovascular (HR, 1.54; 95% CI, 1.05-2.27), and respiratory causes (HR, 3.62; 95% CI, 1.30-10.09) were higher in patients with baseline viral load >5 log copies/mL than in other patients. Rates of each cause of death were higher in patients with presumed transmission via injection drug use than in other patients, with marked increases in rates of liver-related (HR for injection drug use vs non-injection drug use, 6.06; 95% CI, 4.03-9.09) and respiratory tract-related (HR, 4.94; 95% CI, 1.96-12.45) mortality. The proportion of deaths classified as AIDS related decreased with increasing duration of ART. CONCLUSIONS: Important contributors to non-AIDS mortality in treated HIV-1-infected individuals must be addressed if decreases in mortality rates are to continue

The association between hepatitis C virus (HCV) infection and coronary artery disease (CAD) is controversial. We conducted this study to determine and quantify this association.We used an established, national, observational cohort of all HCV-infected veterans receiving care at all Veterans Affairs facilities, the Electronically Retrieved Cohort of HCV Infected Veterans, to identify HCV-infected subjects and HCV-uninfected control subjects. We used the Cox proportional-hazards model to determine the risk of CAD among HCV-infected subjects and control subjects.We identified 82,083 HCV-infected and 89,582 HCV-uninfected subjects. HCV-infected subjects were less likely to have hypertension, hyperlipidemia, and diabetes but were more likely to abuse alcohol and drugs and to have renal failure and anemia. HCV-infected subjects had lower mean (+/- standard deviation) total plasma cholesterol (175 +/- 40.8 mg/dL vs. 198 +/- 41.0 mg/dL), low-density lipoprotein cholesterol (102 +/- 36.8 mg/dL vs. 119 +/- 38.2 mg/dL), and triglyceride (144 +/- 119 mg/dL vs. 179 +/- 151 mg/dL) levels, compared with HCV-uninfected subjects (P.001 for all comparisons). In multivariable analysis, HCV infection was associated with a higher risk of CAD (hazard ratio, 1.25; 95% confidence interval, 1.20-1.30). Traditional risk factors (age, hypertension, chronic obstructive pulmonary disease, diabetes, and hyperlipidemia) were associated with a higher risk of CAD in both groups, whereas minority race and female sex were associated with a lower risk of CAD.HCV-infected persons are younger and have lower lipid levels and a lower prevalence of hypertension. Despite a favorable risk profile, HCV infection is associated with a higher risk of CAD after adjustment for traditional risk factors.

Highly active antiretroviral treatment has resulted in dramatically increased life expectancy among patients with HIV infection who are now aging while receiving treatment and are at risk of developing chronic diseases associated with advanced age. Similarities between aging and the courses of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome suggest that HIV infection compresses the aging process, perhaps accelerating comorbidities and frailty. In a workshop organized by the Association of Specialty Professors, the Infectious Diseases Society of America, the HIV Medical Association, the National Institute on Aging, and the National Institute on Allergy and Infectious Diseases, researchers in infectious diseases, geriatrics, immunology, and gerontology met to review what is known about HIV infection and aging, to identify research gaps, and to suggest high priority topics for future research. Answers to the questions posed are likely to help prioritize and balance strategies to slow the progression of HIV infection, to address comorbidities and drug toxicity, and to enhance understanding about both HIV infection and aging.

Patterns of comorbidity among persons with human immunodeficiency virus (HIV) are not well described. We compared comorbidity among veterans with and without HIV infection. The sample consisted of 33,420 HIV-infected veterans and 66,840 HIV-uninfected veterans. We identified and clustered 11 comorbid conditions using validated International Classification of Diseases, 9th Revision, Clinical Modification codes. We defined multimorbidity as the presence of conditions in all clusters. Models restricted to HIV-infected veterans were adjusted for CD4 cell count and viral load. Comorbidity was common (prevalence, 60%-63%), and prevalence varied by HIV status. Differences remained when the veterans were stratified by age. In multivariable analyses, older HIV-infected veterans were more likely to have substance use disorder and multimorbidity. Renal, vascular, and pulmonary diseases were associated with CD4 cell count 200 cells/mm(3). Comorbidity is the rule, and multimorbidity is common among veterans with HIV infection. Patterns of comorbidity differ substantially by HIV status, age, and HIV severity. Primary care guidelines require adaptation for persons with HIV infection.

Human immunodeficiency virus (HIV)-related mortality has decreased because of highly active antiretroviral therapy. As the life expectancy of HIV-infected patients has increased, the management of comorbid disease in such patients has become a more important concern. We examined the level of comfort self-reported by experts in HIV medicine with prescribing medications to HIV-infected patients for hyperlipidemia, diabetes, hypertension, and depression.As part of a larger project (the Veterans Aging Cohort Study), physicians at infectious diseases (ID) clinics and physicians at general medical (GM) clinics were asked to complete a survey requesting information about demographic characteristics, training and certification received, and self-reported comfort with prescribing medications for patients with hyperlipidemia, diabetes, hypertension, and/or depression. Comfort was rated using a 5-point Likert scale, with scores of 4-5 classified as "comfortable."Of 150 attending physicians surveyed, 51 (34%) were ID certified, 33 (22%) were GM certified but practicing at an ID clinic, and 66 were GM certified and practicing at a GM clinic. Comorbid conditions were common among HIV-infected patients treated at the ID clinics (22% of these patients had hyperlipidemia, 17% had diabetes, 40% had hypertension, and 27% had depression). However, comfort with treating these conditions was less among physicians at the ID clinic. For example, comfort treating patients with hyperlipidemia was greater for GM-certified physicians at GM clinics than for GM-certified physicians and ID-certified physicians at ID clinics (98% vs. 73% and 71%, respectively; P.0001 for trend). A similar pattern was seen for treating patients with diabetes and hypertension (P.0001). Comfort with treating patients with depression was generally lower, particularly among physicians at ID clinics (P.0001).We found that ID-certified physicians and GM-certified physicians at ID clinics reported less comfort prescribing medications for common comorbid conditions, compared with generalist physicians at GM clinics, despite a substantial prevalence of these conditions at the ID clinics. Methods are needed to increase physicians' level of comfort for prescribing treatment and/or to facilitate referral to other physicians for treatment.