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Quality of Life Worse for Long-Term Survivors; Frailty/Function worse for >65
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Frailty, physical function, other geriatric syndromes, and quality of life
Stratified by chronological age.
Frailty was more than twice as prevalent in patients 65
or over compared to the other chronological age groups, as shown in Fig 2a. The proportion of patients 65 or over with an SPPB score under 10, which indicates functional impairment, was double that of the other age groups, and the proportion of patients 65 or over with a gait speed of less than 0.8m/s was three times higher than in the younger patients. For patients 65 or over, 18.6% had a gait speed over 1.2m/s. No differences were found among the three chronological age groups (youngest, intermediate age, and 65 or over group) in the prevalence of prefrailty (54.9% vs. 49.7% vs. 55.9%) or falls (13.5% vs.17.9% vs.13.6%). Cognitive impairment, defined as a MOCA test score ≤ 20 points, was twice as prevalent among patients 65 or over than in the other groups, while depressive symptoms, determined by SF-GDS ≥ 6 points, were half that of the younger patients. There were no differences in QOL stratification, but differences were found between patients 65 or over and the youngest of the older adults when asked, "Are you satisfied with your life?" See Fig 2a for more details.
Frailty was twice as high in patients 65 or over than in the younger patients, which is consistent with the nature of frailty phenotype that is intrinsically related to aging and whose pathophysiological substrate is linked to inflammageing [12]. The same occurs with physical impairment, as measured by SPPB and gait speed. Nevertheless, it is worth highlighting that one in five of the patients 65 or over had a gait speed greater than 1.2m/s, which reflects a good health and functional status and suggests better-than-average life expectancy [9]. This fact supports the main objective of this study, which was intended to demonstrate that older adults with HIV are not a homogeneous group, and it is necessary to stratify them with objective measures of physical function and frailty.
Despite the increased burden of comorbidity, there were no differences between LTHS and the HAART-era group patients regarding frailty and physical function. This reveals that frailty and comorbidity are frequent but not necessarily connected [10]. The main characteristic individuals diagnosed with HIV before 1996 share is that they have survived HIV infection despite the lack of effective treatments in the early years of the pandemic while their peers died [30]. A combination of several host and immune factors must be the reason for their survival, and probably for their reduced risk for frailty. In 1995, before HAART appeared, two studies were published demonstrating that LTHS had low levels of HIV-1 in the presence of strong virus-specific immune responses [31] and that those LTHS with high levels of CD4+ cells maintained control of viral replication but lacked the CD8+ cell activities [32]. The immune system's role is one of the stress-response systems that regulates homeostasis [12], and inflammation is consistently associated with frailty [33]. Frailty is defined as a state of decreased reserves resulting in increased vulnerability to adverse outcomes when exposed to stressors. It is more common among those with low CD4 counts or a high HIV viral load [34] and is a risk factor for overall mortality [35]. People surviving HIV would have specific characteristics that made them robust and able to maintain homeostasis within the highly and severe stressful situation of an HIV infection without effective treatment.


Different profiles among older adults with HIV according to their chronological age and the year of HIV diagnosis: The FUNCFRAIL cohort study (GeSIDA 9817)
Fatima Branas et al on behalf of the FUNCRAIL study group

People in their fifties with HIV are considered older adults, but they appear not to be a homogeneous group.
To evaluate the differences among older adults with HIV according to their chronological age and the year of HIV diagnosis.
Cross-sectional study of the FUNCFRAIL cohort. Patients 50 or over with HIV were included and were stratified by both chronological age and the year of HIV diagnosis: before 1996 (long-term HIV survivors [LTHS]) and after 1996. We recorded sociodemographic data, HIV-related factors, comorbidities, frailty, physical function, other geriatric syndromes, and quality of life (QOL).
We evaluated 801 patients. Of these, 24.7% were women, 47.0% were LTHS, and 14.7% were 65 or over. Of the 65 or over patients, 73% were diagnosed after 1996.
Higher rates of comorbidities among LTHS were found, being the more prevalent: COPD, history of cancer, osteoarthritis, depression, and other psychiatric disorders while the more prevalent among the 65 or over patients were: hypertension, diabetes, dyslipidemia, cancer, and osteoarthritis.
LTHS showed a significantly worse QOL. There were no differences by the year of HIV diagnosis regarding frailty and functional impairment (SPPB <10) but they were more than twice as prevalent in the 65 or over patients compared to the other chronological age groups.
A LTHS and a 65 or over person are both "older adults with HIV," but their characteristics and requirements differ markedly. It is mandatory to design specific approaches focused on the real needs of the different profiles.
People in their fifties with HIV are considered older adults because at this age, the immunological recovery is lower and slower after antiretroviral treatment (ART) than in younger people [1] and age-related comorbidities, frailty, and geriatric syndromes become more prevalent [2-4]. Half of the people with HIV nowadays are older adults [5] and predictions point to an exponential increase of this proportion [6]. Characteristics of aging are not homogeneous. At the same chronological age, the health status can be absolutely different [7], considering the World Health Organization's (WHO) definition of health, "the process of developing and maintaining the functional ability that enables wellbeing in older age", which takes into account (beyond comorbidities) the physical function status, the presence of frailty, and the quality of life (QOL) [8]. Frailty and functional impairment have proven to be better predictors of survival than comorbidity per se, specifically of disability-free years of life in the general population [9-11]. Physical frailty is a clinical syndrome defined by five criteria-shrinking, weakness, poor endurance and energy, slowness, and low physical activity level-in which the whole is more than the sum of the parts in terms of predicting adverse health outcomes [12]. Frailty is prevalent in the older adults with HIV, is associated with mortality and is potentially reversible [13-15].Frailty is starting to be proposed as a clinical marker of biological age [7].
The growing number of older adults with HIV is due to ART's success at improving survival for people with HIV and to the increase in the number of new cases diagnosed in this age group [5]. All these people are now considered "older adults with HIV" despite appearing to have different characteristics and needs. Consequently, it is crucial to know if there are differences between older adults with HIV aged 50 years or over, according to their chronological age and the year of HIV diagnosis in terms of HIV variables, comorbidity, and social factors, but also in terms of frailty, physical function, other geriatric syndromes, and QOL. This is the main purpose of our study.
Patients 65 or over were 15% of our sample and 75% of them were in the HAART-era group. They showed no differences from the chronologically younger patients regarding virological response to ART, but did have a significantly lower CD4+ T-cell nadir count were found, which has largely been described among older adults due to the delay in the diagnosis [39] and lower current CD4+ T-cell count. This is consistent with evidence establishing a lower and slower immunological response to ART increasing with chronological age [40]. This mitigated immune response seems to have more to do with age-related aging [41] than with HIV-related immunosenescence since the years with known HIV infection were significantly lower among patients 65 or over.

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