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PWH -Higher Rates of Frailty Transitioning & Deaths
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PWH are at increased risk of transitioning to frailty, and thereby at increased risk of adverse health outcomes. Whether optimizing the management of obesity, comorbidity, or depressive symptoms may modify the risk of becoming frail requires further investigation.. Transitioning between frailty states in any direction occurred in 36% of a total of 1833 visit-pairs. The odds of nonfrail participants transitioning toward frailty were significantly higher for PWH, occurring in 35 PWH (7.3%) and 25 (5.2%) HIV-negative nonfrail participants, respectively (odd ratioHIV 2.19, 95% confidence interval 1.28 to 3.75). The increased risk among PWH was attenuated when sequentially adjusting for waist–hip ratio, number of pre-existent comorbidities, and the presence of depressive symptoms. Thirty-eight deaths were observed overall, with a greater proportion among PWH compared with HIV-negatives (5.2% versus 1.3%). Frailty is conceptualized as a state of decreased physical resilience because ofdeficits across multiple organ systems, which increases the vulnerability for adverse health outcomes such as falls, hospitalization, disability, and death.2,3 In a previous cross-sectional analysis of the AGEhIV cohort, we showed that PWH had a higher prevalence of frailty compared with HIV-negative persons with similar risk characteristics. Moreover, in a subsequent analysis, we found that in our study population with a median age of 52.7 years [interquartile range (IQR) 48.2–59.3], frailty was predictive of both incident comorbidity and mortality, independent of traditional risk factors such as age, comorbidity burden, and tobacco or alcohol use.5
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Frequency, Risk Factors, and Mediators of Frailty Transitions During Long-Term Follow-Up Among People With HIV and HIV-Negative AGEhIV Cohort Participants
JAIDS Jan 2021
The AGEhIV cohort represents a highly treatment-experienced population of PWH with the prolonged duration of HIV infection, lengthy exposure to ART, and excellent levels of viral suppression.
In unadjusted analyses, HIV-positive status was associated with a >2-fold higher odds [odd ratio (ORHIV) 2.19, 95% confidence interval (CI): 1.28 to 3.75, P = 0.004] of transitioning to frailty (Fig. 2). The association between HIV-positive status and an increased odds of transitioning to frailty was largely mediated by adjustment for a higher waist-to-hip-ratio, a higher number of prevalent comorbidities and a higher prevalence of depressive symptoms among PWH. These findings largely resemble those we have reported previously for participants at time of entry into the cohort.4
We advocate that interventions to reduce frailty development should be investigated among our aging HIV patients. Whether increasing the level of physical activity may also prevent transition to frailty and ameliorate its downstream adverse health outcomes, should be investigated among PWH.
In an earlier analysis from our AGEhIV cohort, we reported a significantly higher prevalence of frailty among PWH.4 We now extend these findings by demonstrating that PWH also are more likely to become frail during long-term follow-up. Of note, during the 3 study-visits with 2-year intervals between study-visits, transition to frailty was infrequent and most visit-pairs were nontransitional.10 When transitions between frailty phenotypes did occur, they were mostly among adjacent frailty phenotypes (eg, from robust to prefrail), similar to what has been observed in other studies.6,10 PWH tended to experience slightly more transitions compared with HIV-negative participants, partly explained by HIV-negative participants more often remaining robust and partly because the previously mentioned higher likelihood for PWH to transition to frailty. Importantly, for most participants assessed as being frail, this was the case only once during the study period. We cannot rule out that this may reflect an imprecision of the instrument to assess frailty in our cohort of middle-aged participants. In addition, frailty transitions may have gone unrecognized, given that frailty was only biennially assessed. Nonetheless, despite its dynamic character, we have previously shown that frailty was a strong predictor of mortality and incident comorbidity, with those who were prefrail being at intermediate risk for both outcomes.5
During study follow-up, 35 (3.8%) PWH and 25 (2.7%) HIV-negative participants transitioned to frailty, respectively. For those transitioning to frailty, most were prefrail at the previous study-visit (Fig. 1). Of all participants who were classified as frail during at least one study visit, most of them did so during only a single study visit (78.7%) with most transitioning back to the prefrail state. Thirty-eight deaths were observed overall, with a greater proportion among PWH compared with HIV-negatives (5.2% versus 1.3%).
Higher age, higher number of comorbidities, and having depressive symptoms, were each independently associated with transition to frailty in the multivariable models.
hs-CRP, D-dimer, and I-FABP were associated with transition to frailty in unadjusted models. After adjusting for sociodemographic variables, D-dimer and I-FABP were no longer associated with transitioning to frailty. High-sensitivity CRP remained associated with transitioning to frailty after adjusting for socio-demographics and waist-to-hip-ratio, but lost significance after adjusting for the prevalent number of comorbidities. For PWH, the OR for transitioning to frailty for each centimeter smaller hip-circumference was significant (OR 1.08, 95% CI: 1.02 to 1.14, P = 0.006), but not for HIV-negative participants (OR 0.96, 95% CI: 0.90 to 1.03, P = 0.275).
In unadjusted analysis, older age, a higher number of prevalent comorbidities, and higher level of depression were associated with lower odds of transitioning back from frailty (see Table 4, Supplemental Digital Content, http://links.lww.com/QAI/B551). In multivariable analysis, having a higher number of prevalent comorbidities resulted in a lower OR to transition to robustness
Abstract
Background:
We previously demonstrated a higher prevalence of frailty among AGEhIV-cohort participants with HIV (PWH) than among age- and lifestyle-comparable HIV-negative participants. Furthermore, frailty was associated with the development of comorbidities and mortality. As frailty may be a dynamic state, we evaluated the frequency of transitions between frailty states, and explored which factors were associated with transition toward frailty in this cohort.
Methods:
The study enrolled 598 PWH and 550 HIV-negative participants aged ≥45 years. Of those, 497 and 479 participants, respectively, participated in ≥2 consecutive biennial study-visits between October 2010 and October 2016, contributing 918 and 915 visit-pairs, respectively. We describe the frequency, direction, and risk factors of frailty transitions. Logistic regression models with generalized estimating equations were used to evaluate determinants for transition to frailty, including HIV-status, socio-demographic, behavioral, HIV-related factors, and various inflammatory and related biomarkers.
Results:
Transitioning between frailty states in any direction occurred in 36% of a total of 1833 visit-pairs. The odds of nonfrail participants transitioning toward frailty were significantly higher for PWH, occurring in 35 PWH (7.3%) and 25 (5.2%) HIV-negative nonfrail participants, respectively (odd ratioHIV 2.19, 95% confidence interval 1.28 to 3.75). The increased risk among PWH was attenuated when sequentially adjusting for waist–hip ratio, number of pre-existent comorbidities, and the presence of depressive symptoms.
Conclusion:
PWH are at increased risk of transitioning to frailty, and thereby at increased risk of adverse health outcomes. Whether optimizing the management of obesity, comorbidity, or depressive symptoms may modify the risk of becoming frail requires further investigation.
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