Skip to main content

Advertisement

SpringerLink
Log in

Frailty in HIV: Epidemiology, Biology, Measurement, Interventions, and Research Needs

  • Complications of HIV and Antiretroviral Therapy (G McComsey, Section Editor)
  • Published:
Current HIV/AIDS Reports Aims and scope Submit manuscript

Abstract

Frailty is a critical aging-related syndrome marked by diminished physiologic reserve and heightened vulnerability to stressors, predisposing to major adverse clinical outcomes, including hospitalization, institutionalization, disability, and death in the general population of older adults. As the proportion of older adults living with HIV increases in the era of antiretroviral therapy, frailty is increasingly recognized to be of significant clinical and public health relevance to the HIV-infected population. This article reviews current knowledge on the epidemiology and biology of frailty and its potential role as a target for reducing disparities in outcomes in HIV; conceptual frameworks and current approaches to frailty measurement; existing data on frailty interventions; and important areas for future research focus necessary to develop and advance effective strategies to prevent or ameliorate frailty and its marked adverse consequences among people living with HIV.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Mills EJ, Barnighausen T, Negin J. HIV and aging—preparing for the challenges ahead. N Engl J Med. 2012;366(14):1270–3.

    Article  CAS  PubMed  Google Scholar 

  2. Smit M, Brinkman K, Geerlings S, Smit C, Thyagarajan K, Sighem A, et al. Future challenges for clinical care of an ageing population infected with HIV: a modelling study. Lancet Infect Dis. 2015;15(7):810–8.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Chow FC, Regan S, Feske S, Meigs JB, Grinspoon SK, Triant VA. Comparison of ischemic stroke incidence in HIV-infected and non-HIV-infected patients in a US health care system. J Acquir Immune Defic Syndr. 2012;60(4):351–8.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Drummond MB, Kirk GD. HIV-associated obstructive lung diseases: insights and implications for the clinician. Lancet Respir Med. 2014;2(7):583–92.

    Article  PubMed  PubMed Central  Google Scholar 

  5. El-Sadr WM, Lundgren JD, Neaton JD, Gordin F, Abrams D, Arduino RC, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355(22):2283–96.

    Article  CAS  PubMed  Google Scholar 

  6. Guaraldi G, Silva AR, Stentarelli C. Multimorbidity and functional status assessment. Curr Opin HIV AIDS. 2014;9(4):386–97.

    Article  PubMed  Google Scholar 

  7. High KP, Brennan-Ing M, Clifford DB, Cohen MH, Currier J, Deeks SG, et al. HIV and aging: state of knowledge and areas of critical need for research. A report to the NIH Office of AIDS Research by the HIV and Aging Working Group. J Acquir Immune Defic Syndr. 2012;60 Suppl 1:S1–18.

    Article  CAS  PubMed  Google Scholar 

  8. Kirk GD, Mehta SH, Astemborski J, Galai N, Washington J, Higgins Y, et al. HIV, age, and the severity of hepatitis C virus-related liver disease: a cohort study. Ann Intern Med. 2013;158(9):658–66.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lucas GM, Ross MJ, Stock PG, Shlipak MG, Wyatt CM, Gupta SK, et al. Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis: Off Publ Infect Dis Soc Am. 2014;59(9):e96–138.

    Article  Google Scholar 

  10. Monroe AK, Glesby MJ, Brown TT. Diagnosing and managing diabetes in HIV-infected patients: current concepts. Clin Infect Dis: Off Publ Infect Dis Soc Am. 2015;60(3):453–62.

    Article  Google Scholar 

  11. Nightingale S, Winston A, Letendre S, Michael BD, McArthur JC, Khoo S, et al. Controversies in HIV-associated neurocognitive disorders. Lancet Neurol. 2014;13(11):1139–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Nou E, Lo J, Hadigan C, Grinspoon SK. Pathophysiology and management of cardiovascular disease in patients with HIV. Lancet Diabetes Endocrinol. 2016.

  13. Shiels MS, Cole SR, Kirk GD, Poole C. A meta-analysis of the incidence of non-AIDS cancers in HIV-infected individuals. J Acquir Immune Defic Syndr. 2009;52(5):611–22.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Sico JJ, Chang CC, So-Armah K, Justice AC, Hylek E, Skanderson M, et al. HIV status and the risk of ischemic stroke among men. Neurology. 2015;84(19):1933–40.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Silverberg MJ, Lau B, Achenbach CJ, Jing Y, Althoff KN, D’Souza G, et al. Cumulative incidence of cancer among persons with HIV in North America: a cohort study. Ann Intern Med. 2015;163(7):507–18.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Bortz 2nd WM. A conceptual framework of frailty: a review. J Gerontol A Biol Sci Med Sci. 2002;57(5):M283–8.

    Article  PubMed  Google Scholar 

  17. Buchner DM, Wagner EH. Preventing frail health. Clin Geriatr Med. 1992;8(1):1–17.

    CAS  PubMed  Google Scholar 

  18. 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 A Biol Sci Med Sci. 2004;59(3):255–63.

    Article  PubMed  Google Scholar 

  19. Hogan DB, MacKnight C, Bergman H. Steering Committee CIoF, aging. Models, definitions, and criteria of frailty. Aging Clin Exp Res. 2003;15(3 Suppl):1–29.

    PubMed  Google Scholar 

  20. Morley JE, Vellas B, van Kan GA, Anker SD, Bauer JM, Bernabei R, et al. Frailty consensus: a call to action. J Am Med Dir Assoc. 2013;14(6):392–7.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Rodriguez-Manas L, Feart C, Mann G, Vina J, Chatterji S, Chodzko-Zajko W, et al. Searching for an operational definition of frailty: a Delphi method based consensus statement: the frailty operative definition-consensus conference project. J Gerontol A Biol Sci Med Sci. 2013;68(1):62–7.

    Article  PubMed  Google Scholar 

  22. Varadhan R, Seplaki CL, Xue QL, Bandeen-Roche K, Fried LP. Stimulus–response paradigm for characterizing the loss of resilience in homeostatic regulation associated with frailty. Mech Ageing Dev. 2008;129(11):666–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Walston JD, Bandeen-Roche K. Frailty: a tale of two concepts. BMC Med. 2015;13:185.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Erlandson KM, Schrack JA, Jankowski CM, Brown TT, Campbell TB. Functional impairment, disability, and frailty in adults aging with HIV-infection. Curr HIV/AIDS Rep. 2014;11(3):279–90.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Bortz W. Understanding frailty. J Gerontol A Biol Sci Med Sci. 2010;65(3):255–6. discussion 7.

    Article  PubMed  Google Scholar 

  26. Buta BJ, Walston JD, Godino JG, Park M, Kalyani RR, Xue QL, et al. Frailty assessment instruments: systematic characterization of the uses and contexts of highly-cited instruments. Ageing Res Rev. 2015;26:53–61.

    Article  PubMed  Google Scholar 

  27. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–56.

    Article  CAS  PubMed  Google Scholar 

  28. Bandeen-Roche K, Xue QL, Ferrucci L, Walston J, Guralnik JM, Chaves P, et al. Phenotype of frailty: characterization in the women’s health and aging studies. J Gerontol A Biol Sci Med Sci. 2006;61(3):262–6.

    Article  PubMed  Google Scholar 

  29. Mitnitski AB, Mogilner AJ, Rockwood K. Accumulation of deficits as a proxy measure of aging. TheScientificWorldJOURNAL. 2001;1:323–36.

    Article  CAS  PubMed  Google Scholar 

  30. Mitnitski AB, Song X, Rockwood K. The estimation of relative fitness and frailty in community-dwelling older adults using self-report data. J Gerontol A Biol Sci Med Sci. 2004;59(6):M627–32.

    Article  PubMed  Google Scholar 

  31. Rockwood K, Andrew M, Mitnitski A. A comparison of two approaches to measuring frailty in elderly people. J Gerontol A Biol Sci Med Sci. 2007;62(7):738–43.

    Article  PubMed  Google Scholar 

  32. Rockwood K, Mitnitski A. Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci. 2007;62(7):722–7.

    Article  PubMed  Google Scholar 

  33. Rockwood K, Mitnitski A, Song X, Steen B, Skoog I. Long-term risks of death and institutionalization of elderly people in relation to deficit accumulation at age 70. J Am Geriatr Soc. 2006;54(6):975–9.

    Article  PubMed  Google Scholar 

  34. Rockwood K, Song X, Mitnitski A. Changes in relative fitness and frailty across the adult lifespan: evidence from the Canadian National Population Health Survey. CMAJ: Can Med Assoc J = J Assoc Med Can. 2011;183(8):E487–94.

    Article  Google Scholar 

  35. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381(9868):752–62.

    Article  PubMed  Google Scholar 

  36. Xue QL. The frailty syndrome: definition and natural history. Clin Geriatr Med. 2011;27(1):1–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Bandeen-Roche K, Seplaki CL, Huang J, Buta B, Kalyani RR, Varadhan R, et al. Frailty in older adults: a nationally representative profile in the United States. J Gerontol A Biol Sci Med Sci. 2015;70(11):1427–34.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Alvarado BE, Zunzunegui MV, Beland F, Bamvita JM. Life course social and health conditions linked to frailty in Latin American older men and women. J Gerontol A Biol Sci Med Sci. 2008;63(12):1399–406.

    Article  PubMed  Google Scholar 

  39. Desquilbet L, Jacobson LP, Fried LP, Phair JP, Jamieson BD, Holloway M, 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(11):1279–86.

    Article  PubMed  Google Scholar 

  40. Desquilbet L, Margolick JB, Fried LP, Phair JP, Jamieson BD, Holloway M, 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(3):299–306.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Althoff KN, Jacobson LP, Cranston RD, Detels R, Phair JP, Li X, et al. Age, comorbidities, and AIDS predict a frailty phenotype in men who have sex with men. J Gerontol A Biol Sci Med Sci. 2014;69(2):189–98.

    Article  PubMed  Google Scholar 

  42. Gustafson DR, Shi Q, Thurn M, Holman S, Minkoff H, Cohen M, et al. Frailty and constellations of factors in aging HIV-infected and uninfected women—the Women’s Interagency HIV Study. J Frailty Aging. 2016;5(1):43–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Kooij KW, Wit FW, Schouten J, van der Valk M, Godfried MH, Stolte IG, et al. HIV infection is independently associated with frailty in middle-aged HIV type 1-infected individuals compared with similar but uninfected controls. Aids. 2016;30(2):241–50.

    Article  CAS  PubMed  Google Scholar 

  44. Onen NF, Agbebi A, Shacham E, Stamm KE, Onen AR, Overton ET. Frailty among HIV-infected persons in an urban outpatient care setting. J Infect. 2009;59(5):346–52.

    Article  PubMed  Google Scholar 

  45. Onen NF, Patel P, Baker J, Conley L, Brooks JT, Bush T, et al. Frailty and pre-frailty in a contemporary cohort of HIV-infected adults. J Frailty Aging. 2014;3(3):158–65.

    CAS  PubMed  Google Scholar 

  46. Pathai S, Gilbert C, Weiss HA, Cook C, Wood R, Bekker LG, et al. Frailty in HIV-infected adults in South Africa. J Acquir Immune Defic Syndr. 2013;62(1):43–51.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Piggott DA, Muzaale AD, Mehta SH, Brown TT, Patel KV, Leng SX, et al. Frailty, HIV infection, and mortality in an aging cohort of injection drug users. PLoS One. 2013;8(1):e54910.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Rees HC, Ianas V, McCracken P, Smith S, Georgescu A, Zangeneh T, et al. Measuring frailty in HIV-infected individuals. Identification of frail patients is the first step to amelioration and reversal of frailty. J Vis Exp: JoVE. 2013;(77).

  49. Terzian AS, Holman S, Nathwani N, Robison E, Weber K, Young M, et al. Factors associated with preclinical disability and frailty among HIV-infected and HIV-uninfected women in the era of cART. J Womens Health (Larchmt). 2009;18(12):1965–74.

    Article  Google Scholar 

  50. Erlandson KM, Allshouse AA, Jankowski CM, Duong S, Mawhinney S, Kohrt WM, et al. Comparison of functional status instruments in HIV-infected adults on effective antiretroviral therapy. HIV Clin Trials. 2012;13(6):324–34.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Guaraldi G, Brothers TD, Zona S, Stentarelli C, Carli F, Malagoli A, et al. A frailty index predicts survival and incident multimorbidity independent of markers of HIV disease severity. Aids. 2015;29(13):1633–41.

    Article  PubMed  Google Scholar 

  52. Justice AC, McGinnis KA, Skanderson M, Chang CC, Gibert CL, Goetz MB, et al. Towards a combined prognostic index for survival in HIV infection: the role of ‘non-HIV’ biomarkers. HIV Med. 2010;11(2):143–51.

    Article  CAS  PubMed  Google Scholar 

  53. Desquilbet L, Jacobson LP, Fried LP, Phair JP, Jamieson BD, Holloway M, et al. A frailty-related phenotype before HAART initiation as an independent risk factor for AIDS or death after HAART among HIV-infected men. J Gerontol A, Biol Sci Med Sci. 2011.

  54. Akgun KM, Tate JP, Crothers K, Crystal S, Leaf DA, Womack J, et al. An adapted frailty-related phenotype and the VACS index as predictors of hospitalization and mortality in HIV-infected and uninfected individuals. J Acquir Immune Defic Syndr. 2014;67(4):397–404.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Erlandson KM, Allshouse AA, Jankowski CM, Duong S, MaWhinney S, Kohrt WM, et al. Risk factors for falls in HIV-infected persons. J Acquir Immune Defic Syndr. 2012;61(4):484–9.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Pathai S, Bajillan H, Landay AL, High KP. Is HIV a model of accelerated or accentuated aging? J Gerontol A Biol Sci Med Sci. 2014;69(7):833–42.

    Article  PubMed  Google Scholar 

  57. Angelovich TA, Hearps AC, Maisa A, Martin GE, Lichtfuss GF, Cheng WJ, et al. Viremic and virologically suppressed HIV infection increases age-related changes to monocyte activation equivalent to 12 and 4 years of aging, respectively. J Acquir Immune Defic Syndr. 2015;69(1):11–7.

    Article  CAS  PubMed  Google Scholar 

  58. Horvath S, Levine AJ. HIV-1 infection accelerates age according to the epigenetic clock. J Infect Dis. 2015;212(10):1563–73.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Levine AJ, Quach A, Moore DJ, Achim CL, Soontornniyomkij V, Masliah E, et al. Accelerated epigenetic aging in brain is associated with pre-mortem HIV-associated neurocognitive disorders. J Neurovirol. 2015.

  60. Liu JC, Leung JM, Ngan DA, Nashta NF, Guillemi S, Harris M, et al. Absolute leukocyte telomere length in HIV-infected and uninfected individuals: evidence of accelerated cell senescence in HIV-associated chronic obstructive pulmonary disease. PLoS One. 2015;10(4):e0124426.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Althoff KN, McGinnis KA, Wyatt CM, Freiberg MS, Gilbert C, Oursler KK, et al. Comparison of risk and age at diagnosis of myocardial infarction, end-stage renal disease, and non-AIDS-defining cancer in HIV-infected versus uninfected adults. Clin Infect Dis: Off Publ Infect Dis Soc Am. 2015;60(4):627–38.

    Article  Google Scholar 

  62. Shiels MS, Pfeiffer RM, Engels EA. Age at cancer diagnosis among persons with AIDS in the United States. Ann Intern Med. 2010;153(7):452–60.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Gill TM, Gahbauer EA, Allore HG, Han L. Transitions between frailty states among community-living older persons. Arch Intern Med. 2006;166(4):418–23.

    Article  PubMed  Google Scholar 

  64. Harttgen K, Kowal P, Strulik H, Chatterji S, Vollmer S. Patterns of frailty in older adults: comparing results from higher and lower income countries using the Survey of Health, Ageing and Retirement in Europe (SHARE) and the Study on Global AGEing and Adult Health (SAGE). PLoS One. 2013;8(10):e75847.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Herr M, Robine JM, Aegerter P, Arvieu JJ, Ankri J. Contribution of socioeconomic position over life to frailty differences in old age: comparison of life-course models in a French sample of 2350 old people. Ann Epidemiol. 2015;25(9):674–80 e1.

    Article  PubMed  Google Scholar 

  66. Soler-Vila H, Garcia-Esquinas E, Leon-Munoz LM, Lopez-Garcia E, Banegas JR, Rodriguez-Artalejo F. Contribution of health behaviours and clinical factors to socioeconomic differences in frailty among older adults. J Epidemiol Community Health. 2016;70(4):354–60.

    Article  PubMed  Google Scholar 

  67. Szanton SL, Seplaki CL, Thorpe Jr RJ, Allen JK, Fried LP. Socioeconomic status is associated with frailty: the women’s health and aging studies. J Epidemiol Community Health. 2010;64(1):63–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Hall HI, An Q, Tang T, Song R, Chen M, Green T, et al. Prevalence of diagnosed and undiagnosed HIV infection—United States, 2008–2012. MMWR Morb Mortal Wkly Rep. 2015;64(24):657–62.

    PubMed  Google Scholar 

  69. Bachhuber MA, Southern WN. Hospitalization rates of people living with HIV in the United States, 2009. Public Health Rep. 2014;129(2):178–86.

    PubMed  PubMed Central  Google Scholar 

  70. Lesko CR, Cole SR, Miller WC, Westreich D, Eron JJ, Adimora AA, et al. Ten-year survival by race/ethnicity and sex among treated, HIV-infected adults in the United States. Clin Infect Dis: Off Publ Infect Dis Soc Am. 2015;60(11):1700–7.

    Article  Google Scholar 

  71. Linley L, Prejean J, An Q, Chen M, Hall HI. Racial/ethnic disparities in HIV diagnoses among persons aged 50 years and older in 37 US States, 2005–2008. Am J Public Health. 2012;102(8):1527–34.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Losina E, Schackman BR, Sadownik SN, Gebo KA, Walensky RP, Chiosi JJ, et al. Racial and sex disparities in life expectancy losses among HIV-infected persons in the united states: impact of risk behavior, late initiation, and early discontinuation of antiretroviral therapy. Clin Infect Dis: Off Publ Infect Dis Soc Am. 2009;49(10):1570–8.

    Article  Google Scholar 

  73. Millett GA, Peterson JL, Flores SA, Hart TA, Jeffries WL, Wilson PA, et al. Comparisons of disparities and risks of HIV infection in black and other men who have sex with men in Canada, UK, and USA: a meta-analysis. Lancet. 2012;380(9839):341–8.

    Article  PubMed  Google Scholar 

  74. Rosenberg ES, Millett GA, Sullivan PS, Del Rio C, Curran JW. Understanding the HIV disparities between black and white men who have sex with men in the USA using the HIV care continuum: a modeling study. Lancet HIV. 2014;1(3):e112–e8.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Siddiqi AE, Hu X, Hall HI. Centers for disease C, prevention. Mortality among blacks or African Americans with HIV infection—United States, 2008–2012. MMWR Morb Mortal Wkly Rep. 2015;64(4):81–6.

    PubMed  Google Scholar 

  76. Simard EP, Fransua M, Naishadham D, Jemal A. The influence of sex, race/ethnicity, and educational attainment on human immunodeficiency virus death rates among adults, 1993–2007. Arch Intern Med. 2012;172(20):1591–8.

    Article  PubMed  Google Scholar 

  77. Fedarko NS. The biology of aging and frailty. Clin Geriatr Med. 2011;27(1):27–37.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Fried LP, Hadley EC, Walston JD, Newman AB, Guralnik JM, Studenski S, et al. From bedside to bench: research agenda for frailty. Sci Aging knowl Environ: SAGE KE. 2005;2005(31):e24.

    Article  Google Scholar 

  79. Walston J, Hadley EC, Ferrucci L, Guralnik JM, Newman AB, Studenski SA, et al. Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults. J Am Geriatr Soc. 2006;54(6):991–1001.

    Article  PubMed  Google Scholar 

  80. Ances BM, Vaida F, Yeh MJ, Liang CL, Buxton RB, Letendre S, et al. HIV infection and aging independently affect brain function as measured by functional magnetic resonance imaging. J Infect Dis. 2010;201(3):336–40.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Walston J. Frailty—the search for underlying causes. Sci Aging Knowl Environ: SAGE KE. 2004;2004(4):e4.

    Article  Google Scholar 

  82. Beaupere C, Garcia M, Larghero J, Feve B, Capeau J, Lagathu C. The HIV proteins Tat and Nef promote human bone marrow mesenchymal stem cell senescence and alter osteoblastic differentiation. Aging Cell. 2015;14(4):534–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Effros RB, Allsopp R, Chiu CP, Hausner MA, Hirji K, Wang LL, et al. Shortened telomeres in the expanded CD28–CD8+ cell subset in HIV disease implicate replicative senescence in HIV pathogenesis. Aids. 1996;10(8):F17–22.

    Article  CAS  PubMed  Google Scholar 

  84. Erlandson KM, Allshouse AA, Jankowski CM, Lee EJ, Rufner KM, Palmer BE, et al. Association of functional impairment with inflammation and immune activation in HIV type 1-infected adults receiving effective antiretroviral therapy. J Inf Dis. 2013;208(2):249–59.

    Article  CAS  Google Scholar 

  85. Jain S, Desai N, Bhangoo A. Pathophysiology of GHRH-growth hormone-IGF1 axis in HIV/AIDS. Rev Endocr Metab Disord. 2013;14(2):113–8.

    Article  CAS  PubMed  Google Scholar 

  86. Maagaard A, Kvale D. Mitochondrial toxicity in HIV-infected patients both off and on antiretroviral treatment: a continuum or distinct underlying mechanisms? J Antimicrob Chemother. 2009;64(5):901–9.

    Article  CAS  PubMed  Google Scholar 

  87. Payne BA, Wilson IJ, Hateley CA, Horvath R, Santibanez-Koref M, Samuels DC, et al. Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations. Nat Genet. 2011;43(8):806–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Perrin S, Cremer J, Roll P, Faucher O, Menard A, Reynes J, et al. HIV-1 infection and first line ART induced differential responses in mitochondria from blood lymphocytes and monocytes: the ANRS EP45 “Aging” study. PLoS One. 2012;7(7):e41129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Smith RL, de Boer R, Brul S, Budovskaya Y, van Spek H. Premature and accelerated aging: HIV or HAART? Front Genet. 2012;3:328.

    PubMed  Google Scholar 

  90. Wolthers KC, Wisman GBA, Otto SA, Husman AMD, Schaft N, de Wolf F. T cell telomere length in HIV-1 infection: no evidence for increased CD4(+) T cell turnover. Science. 1996;274(5292):1543–7.

    Article  CAS  PubMed  Google Scholar 

  91. Leng SX, Xue QL, Tian J, Walston JD, Fried LP. Inflammation and frailty in older women. J Am Geriatr Soc. 2007;55(6):864–71.

    Article  PubMed  Google Scholar 

  92. Singh T, Newman AB. Inflammatory markers in population studies of aging. Ageing Res Rev. 2011;10(3):319–29.

    Article  CAS  PubMed  Google Scholar 

  93. Walston J, McBurnie MA, Newman A, Tracy RP, Kop WJ, Hirsch CH, et al. Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the cardiovascular health study. Arch Intern Med. 2002;162(20):2333–41.

    Article  PubMed  Google Scholar 

  94. Yao X, Li H, Leng SX. Inflammation and immune system alterations in frailty. Clin Geriatr Med. 2011;27(1):79–87.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Deeks SG. HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med. 2011;62:141–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Erlandson KM, Campbell TB. Inflammation in chronic HIV infection: what can we do? J Infect Dis. 2015;212(3):339–42.

    Article  PubMed  Google Scholar 

  97. Zapata HJ, Shaw AC. Aging of the human innate immune system in HIV infection. Curr Opin Immunol. 2014;29C:127–36.

    Article  CAS  Google Scholar 

  98. Hunt PW, Sinclair E, Rodriguez B, Shive C, Clagett B, Funderburg N, et al. Gut epithelial barrier dysfunction and innate immune activation predict mortality in treated HIV infection. J Infect Dis. 2014;210(8):1228–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Tenorio AR, Zheng Y, Bosch RJ, Krishnan S, Rodriguez B, Hunt PW, et al. Soluble markers of inflammation and coagulation but not T-cell activation predict non-AIDS-defining morbid events during suppressive antiretroviral treatment. J Infect Dis. 2014;210(8):1248–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Piggott DA, Varadhan R, Mehta SH, Brown TT, Li H, Walston JD, et al. Frailty, inflammation, and mortality among persons aging with HIV infection and injection drug use. J Gerontol A Biol Sci Med Sci. 2015;70(12):1542–7.

    Article  PubMed  Google Scholar 

  101. Yarasheski KE, Pak-Loduca J, Hasten DL, Obert KA, Brown MB, Sinacore DR. Resistance exercise training increases mixed muscle protein synthesis rate in frail women and men ≥76 yr old. Am J Phys. 1999;277(1 Pt 1):E118–25.

    CAS  Google Scholar 

  102. Liu CK, Fielding RA. Exercise as an intervention for frailty. Clin Geriatr Med. 2011;27(1):101–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. de Labra C, Guimaraes-Pinheiro C, Maseda A, Lorenzo T, Millan-Calenti JC. Effects of physical exercise interventions in frail older adults: a systematic review of randomized controlled trials. BMC Geriatr. 2015;15:154.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Fried LP. Interventions for human frailty: physical activity as a model. Cold Spring Harbor Perspect Med. 2016. doi: 10.1101/cshperspect.a025916.

  105. Binder EF, Schechtman KB, Ehsani AA, Steger-May K, Brown M, Sinacore DR, et al. Effects of exercise training on frailty in community-dwelling older adults: results of a randomized, controlled trial. J Am Geriatr Soc. 2002;50(12):1921–8.

    Article  PubMed  Google Scholar 

  106. Binder EF, Yarasheski KE, Steger-May K, Sinacore DR, Brown M, Schechtman KB, et al. Effects of progressive resistance training on body composition in frail older adults: results of a randomized, controlled trial. J Gerontol A Biol Sci Med Sci. 2005;60(11):1425–31.

    Article  PubMed  Google Scholar 

  107. Tarazona-Santabalbina FJ, Gomez-Cabrera MC, Perez-Ros P, Martinez-Arnau FM, Cabo H, Tsaparas K, et al. A multicomponent exercise intervention that reverses frailty and improves cognition, emotion, and social networking in the community-dwelling frail elderly: a randomized clinical trial. J Am Med Dir Assoc. 2016;17(5):426–33.

    Article  PubMed  Google Scholar 

  108. Yarasheski KE, Scherzer R, Kotler DP, Dobs AS, Tien PC, Lewis CE, et al. Age-related skeletal muscle decline is similar in HIV-infected and uninfected individuals. J Gerontol A Biol Sci Med Sci. 2011;66(3):332–40.

    Article  PubMed  Google Scholar 

  109. Cesari M, Vellas B, Hsu FC, Newman AB, Doss H, King AC, et al. A physical activity intervention to treat the frailty syndrome in older persons-results from the LIFE-P study. J Gerontol A Biol Sci Med Sci. 2015;70(2):216–22.

    Article  PubMed  Google Scholar 

  110. Cameron ID, Fairhall N, Langron C, Lockwood K, Monaghan N, Aggar C, et al. A multifactorial interdisciplinary intervention reduces frailty in older people: randomized trial. BMC Med. 2013;11:65.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Chan DC, Tsou HH, Yang RS, Tsauo JY, Chen CY, Hsiung CA, et al. A pilot randomized controlled trial to improve geriatric frailty. BMC Geriatr. 2012;12:58.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Cesari M, Demougeot L, Boccalon H, Guyonnet S, Vellas B, Andrieu S. The Multidomain Intervention to preveNt disability in ElDers (MINDED) project: rationale and study design of a pilot study. Contemp Clin Trials. 2014;38(1):145–54.

    Article  PubMed  Google Scholar 

  113. Michel JP, Cruz-Jentoft AJ, Cederholm T. Frailty, exercise and nutrition. Clin Geriatr Med. 2015;31(3):375–87.

    Article  PubMed  Google Scholar 

  114. Romera L, Orfila F, Segura JM, Ramirez A, Moller M, Fabra ML, et al. Effectiveness of a primary care based multifactorial intervention to improve frailty parameters in the elderly: a randomised clinical trial: rationale and study design. BMC Geriatr. 2014;14:125.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Morley JE. Developing novel therapeutic approaches to frailty. Curr Pharm Des. 2009;15(29):3384–95.

    Article  CAS  PubMed  Google Scholar 

  116. Gross AL, Xue QL, Bandeen-Roche K, Fried LP, Varadhan R, McAdams-DeMarco MA, et al. Declines and impairment in executive function predict onset of physical frailty. J Gerontol A, Biol Sci Med Sci. 2016.

  117. Halil M, Cemal Kizilarslanoglu M, Emin Kuyumcu M, Yesil Y, Cruz Jentoft AJ. Cognitive aspects of frailty: mechanisms behind the link between frailty and cognitive impairment. J Nutr Health Aging. 2015;19(3):276–83.

    Article  CAS  PubMed  Google Scholar 

  118. Houles M, Canevelli M, van Kan GA, Ousset PJ, Cesari M, Vellas B. Frailty and cognition. J Frailty Aging. 2012;1(2):56–63.

    CAS  PubMed  Google Scholar 

  119. McAdams-DeMarco MA, Tan J, Salter ML, Gross A, Meoni LA, Jaar BG, et al. Frailty and cognitive function in incident hemodialysis patients. Clin J Am Soc Nephrol: CJASN. 2015;10(12):2181–9.

    Article  PubMed  Google Scholar 

  120. Robertson DA, Savva GM, Kenny RA. Frailty and cognitive impairment—a review of the evidence and causal mechanisms. Ageing Res Rev. 2013;12(4):840–51.

    Article  PubMed  Google Scholar 

  121. Korc-Grodzicki B, Downey RJ, Shahrokni A, Kingham TP, Patel SG, Audisio RA. Surgical considerations in older adults with cancer. J Clin Oncol: Off J Am Soc Clin Oncol. 2014;32(24):2647–53.

    Article  Google Scholar 

  122. Robinson TN, Walston JD, Brummel NE, Deiner S, Brown CH, Kennedy M, et al. Frailty for surgeons: review of a National Institute on Aging Conference on Frailty for Specialists. J Am Coll Surg. 2015;221(6):1083–92.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors were supported by National Institutes of Health grants K23-AI-108357 (DAP), K23 AG050260 (KME), P41-GM103422, P30-DK056341, and P30-DK020579 (KEY).

Author information

Authors and Affiliations

  1. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Damani A. Piggott

  2. Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, MD, USA

    Damani A. Piggott

  3. Department of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, CO, USA

    Kristine M. Erlandson

  4. Department of Medicine, Washington University School of Medicine, 660 South Euclid Ave, Campus Box 8127, St. Louis, MO, 63110, USA

    Kevin E. Yarasheski

Authors
  1. Damani A. Piggott
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kristine M. Erlandson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kevin E. Yarasheski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kevin E. Yarasheski.

Ethics declarations

Conflict of Interest

Damani A. Piggott reports grants from NIH.

Kristine M. Erlandson reports grants from NIH, Gilead, and personal fees from Theratechnologies.

Kevin E. Yarasheski reports grants from NIH, grants and non-financial support from Merck, and consultant fees from EMD Serono.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Complications of Antiretroviral Therapy

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Piggott, D.A., Erlandson, K.M. & Yarasheski, K.E. Frailty in HIV: Epidemiology, Biology, Measurement, Interventions, and Research Needs. Curr HIV/AIDS Rep 13, 340–348 (2016). https://doi.org/10.1007/s11904-016-0334-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11904-016-0334-8

Keywords

Search

Navigation