Understanding frailty, aging, and inflammation in HIV infection.
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ABSTRACT:
SUBMITTER: Leng SX
PROVIDER: S-EPMC4751047 | biostudies-literature | 2015 Mar
REPOSITORIES: biostudies-literature
Publications
Understanding frailty, aging, and inflammation in HIV infection.
Leng Sean X SX Margolick Joseph B JB
Current HIV/AIDS reports 20150301 1
Frailty is a clinical syndrome initially characterized in geriatric populations with a hallmark of age-related declines in physiologic reserve and function and increased vulnerability to adverse health outcomes. Recently, frailty has increasingly been recognized as a common and important HIV-associated non-AIDS (HANA) condition. This article provides an overview of our current understanding of frailty and its phenotypic characteristics and evidence that they are related to aging and to chronic i ...[more]
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Project description:BACKGROUND:Serum markers of inflammation increase with age and have been strongly associated with adverse clinical outcomes among both HIV-infected and uninfected adults. Yet, limited data exist on the predictive and clinical utility of aggregate measures of inflammation. This study sought to evaluate the relationship of a recently validated aggregate inflammatory index with frailty and mortality among aging HIV-infected and uninfected injection drug users. METHODS:Frailty was assessed among HIV-infected and uninfected participants in the AIDS Linked to the IntraVenous Experience (ALIVE) cohort study using the five Fried phenotypic criteria: weight loss, exhaustion, low physical activity, decreased grip strength, and slow gait. The aggregate inflammatory index was constructed from serum measures of interleukin-6 and soluble tumor necrosis factor-? receptor-1. Multinomial logistic regression was used to assess the relationship of frailty with inflammation. Cox proportional hazards models were used to estimate risk for all-cause mortality. RESULTS:Among 1,326 subjects, the median age was 48 years and 29% were HIV-infected. Adjusting for sociodemographics, comorbidity, and HIV status, frailty was significantly associated with each standard deviation increase in log interleukin-6 (odds ratio 1.33; 95% CI, 1.09-1.61), log tumor necrosis factor-? receptor-1 (odds ratio 1.25; 95% CI, 1.04-1.51) and inflammatory index score (odds ratio 1.39; 95% CI, 1.14-1.68). Adjusting for sociodemographics, comorbidity, HIV status, and frailty, the inflammatory index score was independently associated with increased mortality (HR 1.65; 95% CI, 1.44-1.89). CONCLUSION:A recently validated, simple, biologically informed inflammatory index is independently associated with frailty and mortality risk among aging HIV-infected and uninfected injection drug users.
| S-EPMC4643614 | biostudies-literature
Project description:BackgroundFrailty is associated with morbidity and premature mortality among elderly HIV-uninfected adults, but the determinants and consequences of frailty in HIV-infected populations remain unclear. We evaluated the correlates of frailty, and the impact of frailty on mortality in a cohort of aging injection drug users (IDUs).MethodsFrailty was assessed using standard criteria among HIV-infected and uninfected IDUs in 6-month intervals from 2005 to 2008. Generalized linear mixed-model analyses assessed correlates of frailty. Cox proportional hazards models estimated risk for all-cause mortality.ResultsOf 1230 participants at baseline, the median age was 48 years and 29% were HIV-infected; the frailty prevalence was 12.3%. In multivariable analysis of 3,365 frailty measures, HIV-infected IDUs had an increased likelihood of frailty (OR, 1.66; 95% CI, 1.24-2.21) compared to HIV-uninfected IDUs; the association was strongest (OR, 2.37; 95% CI, 1.62-3.48) among HIV-infected IDUs with advanced HIV disease (CD4<350 cells/mm3 and detectable HIV RNA). No significant association was seen with less advanced disease. Sociodemographic factors, comorbidity, depressive symptoms, and prescription drug abuse were also independently associated with frailty. Mortality risk was increased with frailty alone (HR 2.63, 95% CI, 1.23-5.66), HIV infection alone (HR 3.29, 95% CI, 1.85-5.88), and being both HIV-infected and frail (HR, 7.06; 95%CI 3.49-14.3).ConclusionFrailty was strongly associated with advanced HIV disease, but IDUs with well-controlled HIV had a similar prevalence to HIV-uninfected IDUs. Frailty was independently associated with mortality, with a marked increase in mortality risk for IDUs with both frailty and HIV infection.
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Project description:BackgroundHospitalization events exact a substantial toll across the age spectrum. Frailty is associated with all-cause hospitalization among HIV-uninfected adults aged 65 years and older. Limited data exist on the frailty relationship to hospitalization among HIV-infected persons or those aged less than 65 years. Comparative investigation of the frailty relationship to specific classes of hospitalizations has rarely been reported among adults of any age. This study sought to determine the frailty relationship to three distinct classes of hospitalization events among HIV-infected persons and their uninfected counterparts.MethodsFrailty was ascertained semiannually among persons with prior injection drug use using the five Fried phenotypic domains. Hospitalization events were categorized using Agency for Healthcare Research and Quality clinical classification software into chronic, infectious, and nonchronic, noninfectious conditions. Cox proportional hazards models were used to examine the frailty relationship to time to first hospitalization event.ResultsAmong 1,303 subjects, mean age was 48 years; 32% were HIV-infected. Adjusting for sociodemographics, comorbidity, substance use, and HIV disease stage, time-updated frailty status was associated with risk for all hospitalization classes. Baseline frailty was significantly associated with all-cause (hazards ratio [HR] 1.41; 95% confidence interval [CI], 1.06, 1.87), chronic (HR 2.13; 95% CI, 1.46, 3.11), and infectious disease hospitalization (HR 2.51; 95% CI, 1.60, 3.91) but not with nonchronic, noninfectious hospitalization risk (HR 1.09; 95% CI, 0.74, 1.61).ConclusionThe frailty phenotype predicts vulnerability to chronic and infectious disease-related hospitalization. Frailty-targeted interventions may mitigate the substantial burden of infectious and chronic disease-related morbidity and health care utilization in HIV-infected and uninfected populations.
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Project description:BackgroundPeople aging with HIV show variable health trajectories. Our objective was to identify longitudinal predictors of frailty severity and mortality among a group aging with HIV.MethodsExploratory analyses employing a multistate transition model, with data from the prospective Modena HIV Metabolic Clinic Cohort Study, based in Northern Italy, begun in 2004. Participants were followed over four years from their first available visit. We included all 963 participants (mean age 46.8±7.1; 29% female; 89% undetectable HIV viral load; median current CD4 count 549, IQR 405-720; nadir CD4 count 180, 81-280) with four-year data. Frailty was quantified using a 31-item frailty index. Outcomes were frailty index score or mortality at four-year follow-up. Candidate predictor variables were baseline frailty index score, demographic (age, sex), HIV-disease related (undetectable HIV viral load, current CD4+ T-cell count, nadir CD4 count, duration of HIV infection, and duration of antiretroviral therapy [ARV] exposure), and behavioral factors (smoking, injection drug use (IDU), and hepatitis C virus co-infection).ResultsFour-year mortality was 3.0% (n = 29). In multivariable analyses, independent predictors of frailty index at follow-up were baseline frailty index (RR 1.06, 95% CI 1.05-1.07), female sex (RR 0.93, 95% CI 0.87-0.98), nadir CD4 cell count (RR 0.96, 95% CI 0.93-0.99), duration of HIV infection (RR 1.06, 95% CI 1.01-1.12), duration of ARV exposure (RR 1.08, 95% CI 1.02-1.14), and smoking pack-years (1.03, 1.01-1.05). Independent predictors of mortality were baseline frailty index (OR 1.19, 1.02-1.38), current CD4 count (0.34, 0.20-0.60), and IDU (2.89, 1.30-6.42).ConclusionsDemographic, HIV-disease related, and social and behavioral factors appear to confer risk for changes in frailty severity and mortality among people aging with HIV.
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| S-EPMC5365031 | biostudies-literature