Frailty, HIV Infection, and Mortality in an Aging Cohort of Injection Drug Users

Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
PLoS ONE (Impact Factor: 3.23). 01/2013; 8(1):e54910. DOI: 10.1371/journal.pone.0054910
Source: PubMed

ABSTRACT

Frailty 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).
Frailty 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.
Of 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).
Frailty 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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    • "Few studies have prospectively investigated consequences of frailty in HIV infection, but these were conducted in specific populations, limiting the generalizability of their results. A study among intravenous drug users found frailty to be associated with mortality[6]and an adapted frailty phenotype was associated with AIDS and mortality among ART-naive HIV-infected individuals[29]and with hospitalization and mortality in HIV-infected and HIV-uninfected veterans[30]. Additionally, frailty defined as the number of accumulated deficits predicted mortality and multimorbidity in HIV-infected individuals[31]. "
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    ABSTRACT: Background: Frailty is an age-related syndrome of decreased physiological reserve and resistance to stressors, associated with increased morbidity and mortality in the general elderly population. An increased prevalence of frailty has been reported amongst HIVinfected individuals. Methods: Fried frailty phenotype was systematically assessed in predominantly virologically suppressed HIV type 1 (HIV-1)-infected and otherwise comparable HIVuninfected participants aged at least 45 at enrollment into the AGEhIV Cohort Study. Multivariable ordinal logistic regression was used to investigate associations between HIV-and antiretroviral therapy-related covariates, markers of inflammation and body composition and prefrailty/frailty. Results: Data were available for 521 HIV-infected and 513 HIV-uninfected individuals. Prevalence of frailty (10.6 versus 2.7%) and prefrailty (50.7 versus 36.3%) were signifi-cantly higher in HIV-infected individuals (P trend <0.001). HIV infection remained statistically significantly associated with prefrailty/frailty after adjustment for age, sex, race/ethnicity, smoking, hepatitis C infection, comorbidities and depression [adjusted odds ratio (ORadj) 2.16, P<0.001]. A higher waist-to-hip ratio attenuated the coefficient of HIV-infected status (ORadj 1.93, P<0.001), but not waist-or hip-circumference individually or markers of inflammation. Within the HIV-infected group, parameters related to body composition were most strongly and independently associated with prefrailty/frailty: current BMI less than 20 kg/m2 (OR 2.83, P<0.001), nadir BMI less than 20 kg/m2 (OR 2.51, P<0.001) and waist-to-hip ratio (OR 1.79 per 0.1 higher, P<0.001). Conclusion: HIV infection was independently associated with prefrailty/frailty in middle-aged HIV-infected patients compared with HIV-uninfected controls. This partly may be mediated by the higher waist-and lower hip-circumference in the HIV-infected individuals, potentially partially caused by lipodystrophy, and in part be a consequence of historic weight loss associated with advanced HIV-disease.
    No preview · Article · Aug 2015 · Experimental Gerontology
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    • "Other areas of active research include human immunodeficiency virus (HIV) infection and aging. In two large-cohort studies of HIV infection, frailty or frailty-related phenotype was shown to have a significant association with mortality and accelerated immune-function deterioration.79–81 In addition, recent studies have shown associations between frailty and cognitive decline and dementia.82–84 "
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    ABSTRACT: Frailty is a common and important geriatric syndrome characterized by age-associated declines in physiologic reserve and function across multiorgan systems, leading to increased vulnerability for adverse health outcomes. Two major frailty models have been described in the literature. The frailty phenotype defines frailty as a distinct clinical syndrome meeting three or more of five phenotypic criteria: weakness, slowness, low level of physical activity, self-reported exhaustion, and unintentional weight loss. The frailty index defines frailty as cumulative deficits identified in a comprehensive geriatric assessment. Significant progress has recently been made in understanding the pathogenesis of frailty. Chronic inflammation is likely a key pathophysiologic process that contributes to the frailty syndrome directly and indirectly through other intermediate physiologic systems, such as the musculoskeletal, endocrine, and hematologic systems. The complex multifactorial etiologies of frailty also include obesity and specific diseases. Major clinical applications include risk assessment and stratification. This can be applied to the elderly population in the community and in a variety of care settings. Frailty may also be useful for risk assessment in surgical patients and those with cardiovascular diseases, cancer, or human immunodeficiency virus infection, as well as for assessment of vaccine effectiveness in older adults. Currently, exercise and comprehensive geriatric interdisciplinary assessment and treatment are key interventions for frailty. As understanding of the biologic basis and complexity of frailty further improves, more effective and targeted interventional strategies and innovative geriatric-care models will likely be developed.
    Full-text · Article · Mar 2014 · Clinical Interventions in Aging
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    • "Despite the ineffective elimination of the virus, correct management is accompanied by a growing increase in life expectancy that involves age-related complications. For example, atherosclerosis and other non-communicable diseases develop earlier and more rapidly in HIV patients compared with non-infected individuals of a similar age with similar risk factors [1-3]. "
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    ABSTRACT: Background Chemokines can block viral entry by interfering with HIV co-receptors and are recognised mediators of atherosclerosis development. A number of experimental drugs that inhibit HIV entry arrest the development of atherosclerosis in animal models. We hypothesised that the expression of chemokine receptors in circulating leukocytes is associated with the rate of atherosclerosis progression in HIV-infected patients. Methods The increase in intima-media thickness during a 2-year follow-up was used to classify HIV-infected patients (n = 178) as progressors (n = 142) or non-progressors (n = 36) with respect to atherosclerosis. Logistic regression was used to assess variables associated with atherosclerosis progression. Mutations in the CCR5Δ32, CCR2 64I, and CX3CR1 (T280M and V249I) co-receptors as well as the levels of CCR5, CXCR4, CX3CR1, and CCR2 mRNA expression in circulating leukocytes were analysed as independent variables. Results Among the baseline variables, only genetic variants explained the dichotomous outcome. The expression of CCR2 and CXCR4 did not discriminate between progressors and non-progressors. Conversely, CCR5 and CX3CR1 expression was higher in not only progressors but also patients with detectable viral load. The logistic regression, however, demonstrated a significant role for CCR5 expression as a predictor of atherosclerosis progression (B = 2.1, OR = 8.1, p = 0.04) and a negligible effect for CXC3R1 and CCR2 expression. Conclusions Available CCR5 antagonists should be investigated for their potential to delay the course of atherosclerosis in HIV-infected patients.
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