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Frailty phenotype in older people living with HIV:
concepts, prevention and issues
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Translated into English from French
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- Prevalence of frailty in PHIV is frequent (5% from 28%) and appears earlier than in general population (50 versus 65 years). Almost half of people with HIV present prefrail phenotype before 50 years.
- fragility is defined as accelerated aging
- Early identification of frailty among PLHIV could lead to targeted interventions that can improve overall health status and delay entry into dependency and / or early mortality.
- This prevalence would be at least 5% at age 50, which corresponds to the prevalence found in studies in the general population for those aged 65 and over. More than half of the patients included in HIV cohorts would have a "pre-fragile" phenotype by age 50
- Currently, the value of integrating the measure of frailty into the daily care of PLHIV is not known even though the first feasibility and prediction data are encouraging.
- At the primary care level, early identification of vulnerability among independent PHAs could lead to targeted interventions that can delay the onset of negative health outcomes, such as addiction or early mortality.
Geriatr Psychol Neuropsychiatr Vieil April 2019
FrEdErique Retornaz1,2 Nathalie Petit3,4 Albert Darque3,5 Laure de Decker6 AnaÏs Farcet7 Laurent Chiche2 Isabelle Ravaux3,8 Patricia Enel3,9
1 Institut SIlvermed, Centre gErontologique dEpartemental, Marseille, France 2 UnitE de soins et de recherche en mEdecine interne, Hôpital europEen, Marseille, France
frederique.retornaz@gmail.com 3 Visage Study Group, COREVIH, Hôpital de la Conception, Marseille, France 4 MEdecine interne, gEriatrique et thErapeutique, CHU Sainte Marguerite, Assistance Publique, Marseille, France 5 Pharmacie hospitalière, CHU la Conception, Marseille, France 6 Service de GEriatrie, CHU de Nantes,
Nantes, France 7 Pôle gEriatrique, Centre gErontologique dEpartemental,
Marseille, France 8 Institut hospitalo-universitaire (IHU) mEditerranEe infection et maladies tropicales, Marseille, France
9 Centre d’Etude et de recherche sur les services de santE et la qualitE de
vie, EA 3279, Aix Marseille UniversitE, Marseille, France
* TirEs a part
The life-span of people aging with HIV (PHIV) tends to reach people without infection, reflecting the effectiveness and tolerance of antiretroviral treatment and improvement of multidisciplinary management. Comorbidities or HIV-inflammaging seems to be the main determinants of frailty phenotype in PHIV. Prevalence of frailty in PHIV is frequent (5% from 28%) and appears earlier than in general population (50 versus 65 years). Almost half of people with HIV present prefrail phenotype before 50 years. The usefulness of integrate routinely measures of frailty phenotype is not yet known but several data are encouraging in terms of feasibility and prediction. Early determination of frailty in PHIV could lead to target interventions to improve global health and decrease adverse outcomes such as incapacities and early death.
The increase in life expectancy of people living with HIV (PLHIV) is the result of better management combined with highly active antiretroviral therapy (HAART) to control the virus. But it raises new issues related to the aging of this population [1].
What is the concept of fragility?
The fragility of the elderly is a clinical syndrome that expresses a level of risk [7]. Currently, there is a distinction between "phenotypic fragility", which represents a future risk of pejorative events (risk of death, entry into an institution, loss of autonomy, functional loss, falls or hospitalizations), terms such as dependence and senescence [8, 9]. An elderly person is considered "fragile" when they have accumulated deficiencies in several physiological systems, such as neuromuscular, endocrine or nutritional functions [10]. When exposed to stress, this "fragile" older person will have an increased risk of adverse development. A patient type is easily identifiable clinically. For example, when a patient comes in consultation with a walker, has trouble dressing alone after the clinical examination, has obvious cognitive problems, has multiple chronic diseases, with a long list of medications, it is clear that this patient will be considered "fragile". The slightest additional aggression is likely to precipitate it in a "spiral of decompensation in cascade": functional decompensation or comorbidities, undernutrition, iatrogenic pathologies, confusional syndrome, immobilization syndrome, etc. Nevertheless, there are also patients who do not have disabilities for domestic life, or severe or multiple chronic diseases and who, however, will not withstand even minimal aggression. Most of the time these patients are not identified as clinically "at risk". Many doctors had the unpleasant surprise of seeing a patient "decompensate" after the start of a banal treatment and were soon confronted with the aforementioned decompensations without any evidence of an underlying state of fragility. It is the notion of balance between functional reserves and the level of stress or aggression of a patient that gives clinical relevance to the concept of fragility.
Two main conceptual models of frailty oppose the geriatric community. On the one hand, fragility is defined as accelerated aging in which "deficits" of health are added together: the "fragility index" described by Rockwood is an example [11]. The Rockwood model incorporates many parameters (more than 50 items) and does not clearly distinguish the "fragility" of polypathology and disability. On the other hand, frailty is seen as a medical syndrome, endowed with its own physiopathology (sarcopenia, neuroendocrine dysregulation, immunological dysfunction) [12]: the "fragility phenotype" or "phenotypic fragility". Described by Fried, this is the most widely used example in the literature today (Table 1) [13, 14]. In the "fragility phenotype" type concept, a person is considered fragile when it presents a given number of criteria. Fried's model includes five markers: weakness, low endurance, reduced physical activity, slow walking speed, and unintentional weight loss over the past year. The presence of at least three of these criteria qualifies "fragility" while one or two criteria define prefragility. In his original study, Fried demonstrated that "fragile" and "pre-fragile" people were more at risk of adverse development such as: onset or aggravation of disabilities for domestic life, mobility disorders, falls, hospitalization or death within three years, regardless of their comorbidities or initial disabilities. In both models (Fried and Rockwood), patients are considered vulnerable because they are at risk of unfavorable evolution, but the concept of phenotypic fragility is upstream of disability and differs from polypathology. Fried's fragility phenotype would identify "at-risk" individuals earlier than the frailty index and would appear more relevant when there is a definite chronic condition [15].
Phenotypic Fragility and PLHIV The prevalence of frailty phenotype in
PLWHA varies from 5% to 28% according to the studies [16]. This prevalence would be at least 5% at age 50, which corresponds to the prevalence found in studies in the general population for those aged 65 and over. More than half of the patients included in HIV cohorts would have a "pre-fragile" phenotype by age 50 [17]. Although age is a major determinant of frailty, it does not explain this syndrome alone. Certain chronic diseases or prolonged exposure to an inflammatory state may be one of the main physiological determinants [15]. PHAs develop a number of comorbidities, including cardiometabolic (cardiovascular disease, type 2 diabetes, lipodystrophy, chronic kidney disease), bone (osteoporosis) and carcinology, which themselves share strong links with frailty [18]. Epidemiologically, many cross-sectional studies suggest a relationship between frailty and cardiovascular disease [19-23], frailty and osteoporosis [24, 25], frailty and cancer [26-28]. Fragility and HIV infection share a number of common features with the aging process in uninfected people and younger PHAs. Biologically, there are common pathophysiological factors such as: increased pro-inflammatory markers (IL-6, TNF-α, IL-1β, C-reactive protein), increased procoagulant activity (D -dimer and factor VIII) [29-31], insulin resistance or impaired functioning of the immune system (immunosenescence). These biological processes of the "inflammaging" type could contribute to the increased development of certain chronic pathologies such as osteoporosis / osteopenia, cardiovascular diseases, metabolic pathologies (dyslipidemia, glucose intolerance, etc.), deterioration of cognitive functions, and early signs. fragility among PLHIV.
The first three literature studies in the field of HIV infection incorporating the frailty phenotype were performed by Desquilbet et al. Two of them [32, 33] showed a link between the duration of HIV infection or CD4 count and the presence of frailty markers, regardless of the age of the PLWHA. In the 3rd study, the presence of frailty markers on HAART was a predictor of AIDS or death, regardless of known risk factors such as age, CD4 count, or viral load [34]. Since then, a dozen studies have found a significant association between the fragility phenotype and: some comorbidities: co-infection with hepatitis C [35], diabetes [36], renal failure [36], depression [36-38], cognitive impairment [37, 39]; HIV-related markers: CD4 count, CD4 nadir [36-41], viral load [36, 38], duration of HAART treatment [36], or exposure to antiretrovirals in the protease inhibitor family) [37]; variation in the body mass index [37, 41, 42], low socio-economic status (low educational level [36-38], unemployment or low income [37, 43]. Most recently, in a study that included more than 500 PLHIV older than 50 years, phenotypic frailty was significantly associated only with the presence of pain, with other factors such as comorbidities and HIV-related markers no longer significant. in multivariate analysis [44]. In the ALIVE cohort, which included 1,300 intravenous drug users, one-third of whom were HIV-infected, the presence of the frailty phenotype was significantly associated with mortality (7 times higher risk of death in frail PHAs) [38]. ], proinflammatory markers [45] and hospitalization [46]. This frailty phenotype would occur earlier in PHAs (on average 10 to 15 years) compared to the general population [47]. In addition, certain peculiarities such as the social precariousness context and the presence of depressive symptoms in PLHIV could lead to a decrease in physical and / or cognitive activity, and consequently to the early appearance of signs of frailty [48]. ].
How to prevent this fragility: reflections in terms of nutrition and physical activity
Fragility is an unstable state that can potentially be reversible with targeted interventions [49]. Some interventions in the general population have shown interest in preventing frailty (primary and secondary), such as programs that combine physical activity, nutrition, and cognitive training [50, 51]. A recent review of the literature reviewed physical exercise programs specifically for PLHIV. Programs combining aerobic exercises and resistance exercises would be the most effective for improving body composition (weight, body fat, lean mass, bone density), muscle strength and cardiovascular function. None of these studies were performed in frail patients [52]. All involved supervision by a professional, with at least 2 sessions of 30 minutes per week and an average duration of more than 3 months. Low compliance was one of the main bottlenecks of these programs. The feasibility and generalization of these studies remain to be demonstrated. Many studies have reported nutritional programs for people infected with HIV. Apart from malnutrition-related programs in emerging countries, vitamin D supplementation, the Mediterranean diet and some micronutrient supplementation are associated with improved lipid and nutritional parameters. Nutrition counseling activities may indirectly increase physical activity and cardiovascular risk reduction. Again, no study has been specifically dedicated to fragility [53]. In the current state of our knowledge, no study can say that the fragility phenotype could be reversed by specific interventions in PLHIV or that the successive appearance of different markers of fragility could be delayed.
Challenge and challenges for the care of PLHIV in the future
Currently, the value of integrating the measure of frailty into the daily care of PLHIV is not known even though the first feasibility and prediction data are encouraging. The identification of frailty could be useful in the youngest patients with a greater physiological reserve. Only studies showing that the integration of these parameters changes the prognosis of PLHIV will legitimize the systematic identification of frailty and its integration into routine care. In cohorts that included PHAs before and after the HAART era, the frailty phenotype is associated with CD4 count and viral load [32, 33]. With the introduction of earlier antiretroviral therapy for PLHIV (as currently recommended), the use of new (potentially less toxic) treatment lines could also be part of drug interventions that in the future would limit the emergence of this phenotype.
Conclusion
The overall life expectancy of PLHIV tends to match that of uninfected patients, in particular through access to effective and better tolerated antiretroviral therapy. Whatever its definition, fragility should make it possible to better understand the aging and the heterogeneity of it among PLHIV. The concept of frailty provides the opportunity to describe and determine vulnerability in independent seniors (without disabilities) and apparently healthy, but whose more rapidly adverse evolution is to be identified. At the primary care level, early identification of vulnerability among independent PHAs could lead to targeted interventions that can delay the onset of negative health outcomes, such as addiction or early mortality.
Key points
The increase in life expectancy of people living with HIV (PLHIV) is the result of better care associated with highly active antiretroviral therapy.
The aging of this population raises new issues in care.
The fragility phenotype could be a marker of interindividual variability among PLHIV.
The prevalence of frailty phenotype in PHAs is frequent and early.
Early identification of frailty among PLHIV could lead to targeted interventions that can improve overall health status and delay entry into dependency and / or early mortality.
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