The results of this study suggest that community-dwelling HOA often experience frailty at a much younger age compared to the general older population. Central obesity and fat redistribution are important predictors of frailty among HOA. This is the first study to demonstrate that elevated fat mass, particularly truncal fat, and higher BMI is associated with frailty in the HOA population. Previous studies have shown this relationship in the general older population11;19
. Our study is interesting because frailty in HIV-infected patients is usually conceptualized as being a wasting disorder. Previously, frailty in HIV-infected individuals was commonly observed in the setting of wasting and immunocompromised states with lower CD4 count20;21
. In contrast, our community-dwelling frail subjects were mostly obese and had immune restoration as indicated by higher CD4 count and suppressed viral load.
With the growing prevalence of obesity, the most common phenotype of frailty in the years to come has been described as the obese, disabled older adult12
. Notably, as HIV disease has become a manageable chronic illness, it has been progressively accompanied with an increased prevalence of overweight and obesity more than it is accompanied with wasting22
. Additionally, the long-term treatment with ART contributes to the development of lipodystrophy23
, which is characterized by fat redistribution with relative increase in abdominal fat and frequently accompanied with metabolic dysfunction such as insulin resistance24
. Indeed, HIV-infected individuals have significantly greater amounts of abdominal fat compared to age and BMI matched HIV-uninfected individuals25
. Moreover, excess lipid accumulation in muscle and liver also occurs in HIV-infected individuals compared to HIV-uninfected individuals26
– and is compounded by aging27
. Therefore, it is plausible that the ART-related deleterious body composition changes that HOA experience have significant functional consequences. However, in this pilot study we did not observe an association between stavudine exposure and frailty, despite stavudine having the greatest effect on mitochondrial toxicity and fat redistribution24
. We suspect that it is the cumulative toxicity of antiretroviral agents rather than any one agent alone which explains the relationship between body composition and frailty in this population. Additionally, changes in body composition, particularly the gains in abdominal fat, have cardiovascular disease (CVD) consequences24
. Both clinical and subclinical manifestations of CVD have been found to be independently related to frailty 28
To our knowledge, this is the first study to investigate the relationship between body composition and physical frailty in HOA on ART. The IMF and trunk fat measure we used are surrogate markers of intramyocellular fat and visceral fat respectively29
. These markers were inversely related to global physical performance. Our data suggest that excessive visceral fat hypertrophy and lipolysis contribute to fat infiltration in the muscle, and consequently lead to poor muscle quality and a decline in physical function among HOA. We suspect that the relationship between fat redistribution and physical function is a unique finding in the HOA population because to our best knowledge this has not been reported. We speculate that the relationship between fat redistribution and physical function is mediated by adipokines because ART toxicity alters the hemostatic regulation of adipokines30
. Future studies should investigate the pathophysiologic mechanism of HIV-related frailty.
In this study, the PPT was the major determinant of frailty, thereby suggesting that compromised dynamic muscle performance is the most important contributor to functional limitations in HOA. Further, the 60% frailty rate that we observed in our study is higher compared to the near-15% showed in another study which used a different criteria to assess frailty.7
Indeed, the prevalence of frailty can vary using different frailty criteria. The higher frailty rate seen in the present study can be explained not only by the different frailty criteria used to assess frailty, but also by the use of a sample of convenience. Additionally, more functional seniors may have been unable to participate in the present study due to being employed, or substance abuse issues and mental health concerns. It is important to note that the predictive value of defining frailty using the various frailty criteria have not been validated in this younger population with specific comorbidities such as HIV. Therefore, the frailty criteria used in this study and previous studies may not predict morbidity or mortality in HOA, particularly when controlling for other comorbidities. Future research is needed to validate frailty measures in the HIV population.
The conclusions of our study were limited due to small sample size. It should be noted, however, that we have characterized our subjects comprehensively in regards to their physical function and body composition. Although our study lacked HIV-uninfected controls, we observed that these subjects have significant functional impairments that are comparable in a physiologic sense to that which is sometimes seen in HIV-uninfected subjects 15–20 years older. We realize that the cross-sectional design can only identify associations. Nonetheless, our findings offer insight regarding the functional implications related to the altered body composition in HOA. These findings are particularly important because aging with HIV is an emerging issue in the developed world. HOA represents a new subset of the older population who are at high risk of frailty-related negative consequences. These negative consequences not only increase the burden on clinical care by geriatricians and other health professionals, but also create an additional demand for access to what is an already overburdened health care delivery service. In light of the rise of aging and obesity trends within the HIV-infected population, the benefits and feasibility of interventions such as exercise and diet therapy to ameliorate frailty should be a focus of future clinical research.