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Frailty Syndrome and Disability

Key considerations for people living with HIV

Frailty, disability and polypathology are related conditions that encompass many aspects of ageing. Select a condition to download more information. 


A clinical syndrome of decreased reserve and resistance to stressors 


A physical or mental impairment that substantially limits one or more of the major life activities


The concurrent presence of two or more chronic diseases or conditions

The link between frailty, disability and polypathology

Figure 1: Definitions of frailty, comorbidities (polypathology) and disability, and their major healthcare implications.1


Checklist of frailty criteria

Frailty can be defined as a clinical syndrome in which more than three of the following criteria are present:2–4

  • physical shrinking (unintentional weight loss and loss of muscle mass)
  • self-reported exhaustion
  • weakness
  • slow walking speed
  • low physical activity

Having one or two criteria can be defined as intermediate or pre-frail.2

Table 1: Frailty assessment in the Cardiovascular Health Study (CHS)2

Frailty criteria
(≥3 positive = frailty)
Assessment Score positive cut-off
Slowness Timed 15-foot walk 
(stratified by gender and height) Men:
≥7 seconds if height ≤173cm  
≥6 seconds if height >173cm
≥7 seconds if height ≤159cm    
6 seconds if height >159cm
Weakness Grip strength 
(stratified by gender and BMI) Men:
≤29kg if BMI ≤24            
≤30kg if BMI 24.1–28
≤32kg if BMI >28
≤17kg if BMI ≤23            
≤17.3kg if BMI 23.1–26
≤18kg if BMI 26.1–29      
 ≤21kg if BMI >29
Poor endurance / exhaustion “Everything I do is an effort”
“I cannot get going”
Answer “yes” 3–4 days/week or more
Answer “yes” 3–4 days/week or more
Low physical activity Kcal of energy expended in the last week
on leisure time activity (calculated)
Men: <383 kcal
Women: <270 kcal
Shrinking (weight loss and sarcopenia) Self-reported unintentional weight loss 

Measured unintentional weight
loss during follow up
>10 US pounds in previous year

 >5% of body weight in previous year

BMI = body mass index   

Table 2: Frailty assessment in the Women’s Health Initiative (WHI) Observational Study (OS)4 

Frailty criteria (≥3 positive = frailty) Assessment Score positive for frailty?
Muscle weakness / slow walking speed
(score as 2 points)
Rand-36 Physical Function scale Score <75
Exhaustion Rand-36 Vitality scale Score <55
Low physical activity Kcal of energy expended in the 
last week on leisure time activity
Lowest quartile
Unintentional weight loss Measured weight loss

“In the past 2 years, did you 
lose 5 or more pounds (US)
not on purpose at any time”
>5% of body weight in the past 2 years

AND answer “yes”

Figure 2: The frailty cycle.3

Frailty can be viewed as a cycle.2,3

Checklist of risk factors associated with frailty in the general population

Risk factors associated with frailty include the following:2,5–6

  • older age
  • higher rates of co-morbid chronic diseases and disability
  • sarcopenia
  • use of antidepressants
  • previous opportunistic illness
  • clinical AIDS
  • poorer health
  • unemployment
  • lower education and income.

The frailty-related phenotype

  • HIV infection is strongly associated with the prevalence of a frailty-related phenotype.7
    • Prevalence of the frailty-related phenotype for 55-year-old men infected with HIV for ≤4 years is similar to that of uninfected men aged ≥65 years.7
  • A lower CD4 T-cell count is highly, and significantly, predictive of onset of the frailty-related phenotype in HIV-positive men.
  • The prevalence of the frailty-related phenotype declined by approximately 50% after the introduction of highly active antiretroviral therapy (HAART).5


Figure 3: Relationship between CD4 T-cell count and prevalence of the frailty-related phenotype over time.5


HIV, polypathology and polypharmacy

  • People living with HIV have a higher prevalence of hypertension, which is associated with increased risk of heart attack, heart failure, stroke and kidney disease8
    • stress management and lifestyle modification can reduce systolic blood pressure in patients aged ≥55 years.9
  • Obesity is associated with a higher risk of chronic conditions at older ages, such as cardiovascular disease and diabetes, with a higher risk of premature death8
    • lifestyle modification (≥150 minutes/week activity and loss of ≥7% body weight) is effective in preventing diabetes in older individuals10
    • a lifestyle modification program led to improvement in multiple markers of body composition and cardio-metabolic health in obese individuals11
    • lifestyle modifications recommended by the European AIDS Clinical Society (EACS) are shown below
    • the Framingham tool, and other cardiovascular risk calculators, can be used to assess cardiovascular risk
  • Peak aerobic capacity (VO2peak) is reduced in HIV-infected patients compared with age-matched healthy controls
    • VO2peak is significantly reduced in HIV patients aged ≥50 years compared with patients aged 40–49 years (p=0.01).12 
  • Ageing and HIV have additive effects on brain function
    • functional brain demands in HIV-infected people are equivalent to HIV-negative individuals aged approximately 15–20 years older, based on studies that used functional magnetic resonance imaging (fMRI).13

Table 3: Lifestyle interventions recommended in people living with HIV.14

Reproduced with permission from the European AIDS Clinical Society Guidelines Version 5.4. Prevention and Management of non-infectious comorbidities in HIV. 

Drug metabolism in older patients 

  • Hepatic drug clearance can be reduced by up to 30% in older individuals.15
  • Lipophilic drugs may have an increased volume of distribution with a prolonged half life.15
  • Renal excretion is decreased up to 50% in approximately two thirds of elderly patients.15
  • Two approaches are available for dose correction to account for decreased drug elimination in ageing patients: 16
    • extrarenal elimination fraction (Q0) and age-dependent changes in creatinine clearance
    • decline in total drug clearance (CL)
  • Further information on the above can be found at Pharmacology Corner, a pharmacology website, which provides information on geriatric pharmacology, pharmacokinetics, polypharmacy and related topics.

The challenges of polypharmacy in older patients

  • Polypharmacy is very common among older individuals in the general population,17 and is a known risk factor for morbidity and mortality18
    • polypharmacy in ageing patients is a major problem and a challenge that contributes to costs, confusion, compliance issues, and errors in management.19
    • consequences of polypharmacy include adverse drug effects, drug-drug interactions, disease-drug interactions, food-drug interactions, nutraceutical-drug interactions and medication cascade effects.20
    • polypharmacy has been shown to be a statistically significant predictor of hospitalisation, nursing home placement, death, hypoglycaemia, fractures, impaired mobility, pneumonia, and malnutrition.21
  • The drug and pill burden faced by patients with HIV is considerable,22 irrespective of the further challenges faced by older people living with multiple comorbidities.
  • Charts showing known and predicted drug-drug interactions are available from the HIV drug interactions website.


Tools to assess disability and physical/psychological functioning


  1. Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G: Untangling the concepts of disability, frailty and comorbidity: implications for improved targeting and care. J Gerontol Biol Sci Med Sci. 2004;59:255–263. 
  2. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146–156. 
  3. Fried LP, Xue Q-L, Cappola AR, et al. Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment. J Gerontol A Biol Sci Med Sci. 2009;64:1049–1057. 
  4. Woods NF, LaCroix AZ, Gray SL, et al. Frailty: Emergence and Consequences in Women Aged 65 and Older in the Women's Health Initiative Observational Study. J Am Geriatr Soc. 2005;53:1321–1330.
  5. Desquilbet L, Margolick JB, Fried LP, et al. Relationship between a frailty-related phenotype and progressive deterioration of the immune system in HIV-infected men. J Acquir Immune Defic Syndr. 2009;50:299–306. 
  6. Ruiz M, Cefalu C. Frailty syndrome in patients with HIV infection. Clin Geriatr. 2011;19:46–49. 
  7. Desquilbet L, Jacobson LP, Fried LP, et al. HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty. J Gerontol A Biol Sci Med Sci. 2007;62:1279–1286.
  8. Williams SR, Pham-Kanter G, Leitsch SA. Measures of chronic conditions and diseases associated with aging in the National Social Life, Health, and Aging Project. J Gerontol B Psychol Sci Soc Sci. 2009;64(Suppl 1):i67–75.
  9. Dusek JA, Hibberd PL, Buczynski B, et al. Stress management versus lifestyle modification on systolic hypertension and medication elimination: a randomized trial. J Altern Complement Med. 2008;14:129–138.
  10. Crandall J, Schade D, Ma Y, et al. The influence of age on the effects of lifestyle modification and metformin in prevention of diabetes. J Gerontol A Biol Sci Med Sci. 2006;61:1075–1081.  
  11. Pettman TL, Misan GMH, Owen K, et al. Self-management for obesity and cardio-metabolic fitness: description and evaluation of the lifestyle modification program of a randomised controlled trial. Int J Behav Nutr Phys Act. 2008;5:53. 
  12. Oursler KK, Sorkin JD, Smith BA, Katzel LI. Reduced aerobic capacity and physical functioning in older HIV-infected men. AIDS Res Hum Retroviruses. 2006;22:1113–1121.  
  13. Ances BM, Vaida F, Yeh MJ, et al. HIV and aging independently affect brain function as measured by functional magnetic resonance imaging. J Infect Dis. 2010;201:336–340. 
  14. European AIDS Clinical Society Guidelines Version 5-4. Prevention and Management of non-infectious comorbidities in HIV. Accessed 22 June 2011. 
  15. Klotz U. Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev. 2009;41:67–76. 
  16. Turnheim K. Pharmacokinetic dosage guidelines for elderly subjects. Expert Opin Drug Metab Toxicol. 2005;1:33–48. 
  17. Herrlinger C, Klotz U. Drug metabolism and drug interactions in the elderly. Best Pract Res Clin Gastroenterol. 2001;15:897–918. 
  18. Hajjar ER, Cafiero AC, Hanlon JT. Polypharmacy in elderly patients. Am J Geriatr Pharmacother. 2007;5:345–351. 
  19. Ballentine NH. Polypharmacy in the elderly: maximizing benefit, minimizing harm. Crit Care Nurs Q. 2008;31:40–45. 
  20. Salazar JA, Poon I, Nair M. Clinical consequences of polypharmacy in elderly: expect the unexpected, think the unthinkable. Expert Opin Drug Saf. 2007;6:695–704. 
  21. Frazier SC. Health outcomes and polypharmacy in elderly individuals: an integrated literature review. J Gerontol Nurs. 2005;31:4–11.
  22. Furler MD, Einarson TR, Walmsley S, et al. Polypharmacy in HIV: impact of data source and gender on reported drug utilization. AIDS Patient Care. STDS 2004;18:568–586.