30 January 2020 

High rates of frailty seen among middle-aged and older HIV-positive people in Alberta

  • Health issues such as frailty are a risk for all people as they age, with or without HIV
  • However, an Alberta study identified earlier onset of frailty among people with HIV
  • Researchers noted that frailty risk factors can be modified through prevention and care

Thanks to the widespread availability of potent HIV treatment (ART), AIDS-related deaths and illness are uncommon in Canada and other high-income countries compared to the pre-ART era. The power of ART is so tremendous that scientists increasingly expect many ART users to have near-normal life expectancy.

As ART users get older, they are at risk for the same aging-related health issues as everyone else. One of the aging-related issues that can occur is frailty. In such cases, people have reduced capacity to carry out important activities in everyday life. Over time, frailty can lead to severe limitations.

Scientists at the Southern Alberta Clinic, the regional medical reference centre for HIV care, analysed health-related information from more than 700 HIV-positive people aged 50 and older. The scientists focused on blood tests and other assessments that would be linked to poor health. They also compared the information in their study to a larger study of older HIV-negative Canadians.

The scientists found that some degree of frailty was relatively common in their population and appeared to occur at a younger age than in HIV-negative people. Furthermore, frailty was associated with an increased risk of dying. The scientists stated that healthcare providers should be “aware of the earlier occurrence of frailty in adults living with HIV.” The scientists also propose recommendations and interventions to help improve the lives of HIV-positive people.

Study details

The Alberta scientists focused on general laboratory tests and assessments (weight, height, clinician reports) for producing a frailty score. Altogether they relied on 29 factors for producing a frailty score. The scientists adapted a scoring system that was previously used by a leading HIV clinic in Modena, Italy. The score produced values between 0 and 1; the greater the score, the greater the degree of frailty.

During the two years of the study scientists compared the data they collected from HIV-positive people who died and those who survived.

The average profile of participants upon entering the study was as follows:

  • 85% men, 15% women
  • age – 59 years (ranging from 50 to 92 years)
  • the proportion of people between 50 and 64 years – 82%
  • the proportion of people aged 65 years and older – 18%
  • duration of HIV infection – 18 years
  • duration of using ART – 15 years
  • current CD4+ count – 600 cells/mm3 (although 93% of people had more than 200 cells, 7% had a count of 200 cells or less)
  • proportion with an undetectable viral load (less than 40 copies/mL) – 93%


The vast majority of participants had good HIV care test results: high CD4+ cell counts and suppressed viral loads. However, these good test results masked other issues. For instance, the scientists found that participants aged 65 and older “had significantly higher [average frailty scores] than those [aged] 50 to 64 years.” Also, participants whose lowest-ever CD4+ count fell below the 200-cell mark were more likely to be frail.

Distribution of frailty scores

The scientists divided people into the following frailty categories:

  • non-frail – 25%
  • frail – 20%
  • more frail – 45%
  • most frail – 9%


A total of 24 people (3%) died during the study. The distribution of deaths in the different categories of frailty was as follows:

  • non-frail – 3% (5 out of 182 people)
  • frail – 2% (3 out of 144 people)
  • more frail – 3% (10 out of 323 people)
  • most frail – 9% (6 out of 67 people)

Comparing data between people who survived and those who died, the scientists concluded that people who died were more likely to:

  • be older (64 vs. 59 years)
  • have a greater degree of frailty
  • have lower current CD4+ cell counts (341 vs. 602 cells/mm3)

The scientists found that people who had a current CD4+ count below the 200-cell mark were at increased risk of death compared to people who had higher CD4+ cell counts. Current viral load (undetectable or detectable) did not have any apparent impact on the risk of death in the short- and medium-term (for instance, three people who died had a detectable viral load vs. 21 people who died with an undetectable viral load).

Causes of death

Scientists had access to the causes of death for 22 of the 24 cases. The main causes were as follows:

  • cancer – 41%
  • cardiovascular disease (heart attack, stroke and related complications) – 27%

Comparison to HIV-negative Canadians

The scientists compared data from a study of HIV-negative Canadians and found that the HIV-positive people in the present study who were over the age of 50 were at least twice as likely to have some degree of frailty as HIV-negative Canadians who were, on average, 75 years old.

Risk factors

The design of the Alberta study is unable to find the causes of frailty in their population of HIV-positive people. However, other scientists who study immunology, aging and HIV have previously noted the following points:

1. HIV infection causes chronic and excess inflammation and activation of the immune system. These two processes are vital responses by the immune system to viral and other infections. In the normal course of events, excess inflammation and immune activation mobilize nutrients and cells to help to bring an invading germ under control. After such control has been achieved, the immune system releases chemical signals to dampen inflammation and immune activation to reduce the risk of harm to the body. Initiating and continuing to take ART helps to bring HIV to undetectable levels in the blood. This significantly reduces inflammation and immune activation. However, ART cannot reduce these processes to a low normal level. Some immunologists suspect that chronic HIV-related inflammation and immune activation can, over decades, cause subtle injury to different organ-systems and may contribute to the accelerated aging reported in some people with HIV.

2. It is possible that exposure to older forms of anti-HIV drugs—particularly first-generation drugs such as AZT, d4T and ddI and first-generation members of some other classes (non-nucleosides and protease inhibitors)—may have caused some degree of cellular injury. It is therefore possible that exposure to these drugs may have contributed to accelerated aging in some people.

3. Behaviours such as insufficient physical activity, poor diet, smoking and problematic substance use also could have contributed to an increased risk of health problems.

4. There may have been unmeasured factors that could have contributed to frailty, such as co-infection with the herpes virus CMV (cytomegalovirus).

What is to be done?

Research on HIV and aging is still in its infancy. The Alberta scientists noted that there are some factors that have an impact on frailty that are potentially modifiable. For instance, they encourage earlier diagnosis of HIV (when CD4+ cell counts are relatively high) and “initiation of ART and support reinforcement of adherence to therapy.” Those measures would likely help some people achieve and maintain high CD4+ cell counts. But much more is needed.

Learning from HIV-negative people

Based on published research, the Alberta scientists stated that issues such as “cognitive and physical training, nutritional supplementation, or [a combination of these and other interventions] may improve frailty status in HIV-negative people. One study has suggested that adherence to a Mediterranean diet was associated with reduced frailty in older HIV-negative adults.” Therefore, it is possible that such interventions could undergo testing in HIV-positive people to explore their potential.

The next step for the Alberta scientists is to find out whether frailty scores using their methods could be used to help identify patients who need “confirmatory clinical frailty assessment…those confirmed as frail could then undergo comprehensive geriatric assessment to identify modifiable contributing factors, determine prognosis, and develop a management plan.”

There is still much work to be done by the scientific community when it comes to frailty and HIV. However, the Alberta study is a good first step in the right direction. It has found a high prevalence of frailty and apparently accelerated aging in HIV-positive people. Furthermore, the work done by the Alberta team would be relatively low cost and simple to replicate by other clinical centres in Canada.

Other scientists in Canada are planning or implementing studies about HIV and aging. We will publish information about one such study in the future.


Interventions against frailty may improve the health of HIV-positive peopleCATIE News

Frailty, nerve injury and falls in middle-aged and older HIV-positive peopleCATIE News

What’s causing deaths among HIV-positive people in San Francisco?CATIE News

Italian and U.S. researchers look to the future and explore aging-related issuesCATIE News

Factors linked to falling in middle-aged womenTreatmentUpdate 218

Exercise as medicineTreatmentUpdate 234

—Sean R. Hosein


  1. McMillan JM, Krentz HB, Gill MJ, Hogan DB.. Canadian Geriatrics Journal. 2019;22(4):190–198.
  2. Kelly SG, Wu K, Tassiopoulos K, et al. Frailty is an independent risk factor for mortality, cardiovascular disease, bone disease, and diabetes among aging adults with human immunodeficiency virus. Clinical Infectious Diseases. 2019 Sep 27;69(8):1370-1376.
  3. Desquilbet L, Jacobson LP, Fried LP, et al. HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2007 Nov;62(11):1279-86.
  4. Hosaka KRJ, Greene M, Premeaux TA, et al. Geriatric syndromes in older adults living with HIV and cognitive impairment. Journal of the American Geriatric Society. 2019 Sep;67(9):1913-1916.
  5. Chow DC, Bernas MA, Gangcuangco LM, et al. Frailty is associated with insulin resistance in chronic HIV. Clinical Infectious Diseases. 2019; in press.
  6. Guaraldi G, Zona S, Silva AR, et al. The dynamic association between frailty, CD4 and CD4/CD8 ratio in people aging with HIV. PLoS One. 2019 Feb 14;14(2):e0212283.
  7. Sharma A, Shi Q, Hoover DR, et al. Frailty predicts fractures among women with and at-risk for HIV. AIDS. 2019 Mar 1;33(3):455-463.
  8. 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. JAIDS. 2009 Mar 1;50(3):299-306.
  9. O’Brien KK, Tynan AM, Nixon SA, et al. Effectiveness of progressive resistive exercise (PRE) in the context of HIV: systematic review and meta-analysis using the Cochrane Collaboration protocol. BMC Infectious Diseases. 2017 Apr 12;17(1):268.
  10. Erlandson KM, MaWhinney S, Wilson M, et al. Physical function improvements with moderate or high-intensity exercise among older adults with or without HIV infection. AIDS. 2018 Oct 23;32(16):2317-2326.
  11. Lerner AM, Eisinger RW, Fauci AS. Comorbidities in persons with HIV: The lingering challenge. JAMA. 2020;323(1):19-20.
  12. Leng SX, Margolick JB. Aging, sex, inflammation, frailty, and CMV and HIV infections. Cellular Immunology. 2020; in press.
  13. Althoff KN, Gebo KA, Moore RD, et al. Contributions of traditional and HIV-related risk factors on non-AIDS-defining cancer, myocardial infarction, and end-stage liver and renal diseases in adults with HIV in the USA and Canada: a collaboration of cohort studies. Lancet HIV. 2019 Feb;6(2):e93-e104.
  14. Bally APR, Neeld DK, Lu P, et al. PD-1 expression during acute infection is repressed through an LSD1-blimp-1 axis. Journal of Immunology. 2020; in press.
  15. Hoenigl M, Kessler HH, Gianella S. Editorial: HIV-associated immune activation and persistent inflammation. Frontiers in Immunology. 2019;10:2858.
  16. Furman D, Campisi J, Verdin E, et al. Chronic inflammation in the etiology of disease across the life span. Nature Medicine. 2019;25(12):1822–1832.
  17. Ahadi S, Zhou W, Schüssler-Fiorenza Rose SM, et al. Personal aging markers and ageotypes revealed by deep longitudinal profiling. Nature Medicine. 2020;26(1):83–90.
  18. Ramendra R, Isnard S, Lin J, et al. CMV seropositivity is associated with increased microbial translocation in people living with HIV and uninfected controls. Clinical Infectious Diseases. 2020; in press.
  19. Isnard S, Ramendra R, Dupuy FP, et al. Plasma levels of C-type lectin REG3α and gut damage in people with human immunodeficiency virus. Journal of Infectious Diseases. 2020;221(1):110–121.
  20. Belkina AC, Starchenko A, Drake KA, et al. Multivariate computational analysis of gamma delta T cell inhibitory receptor signatures reveals the divergence of healthy and ART-suppressed HIV+ aging. Frontiers in Immunology. 2018;9:2783.
  21. Deguit CDT, Hough M, Hoh R, et al. Some aspects of CD8+ T-cell exhaustion are associated with altered T-cell mitochondrial features and ROS content in HIV infection. Journal of Acquired Immune Deficiency Syndromes. 2019;82(2):211–219.
  22. Lagathu C, Béréziat V, Gorwood J, et al. Metabolic complications affecting adipose tissue, lipid and glucose metabolism associated with HIV antiretroviral treatment. Expert Opinion in Drug Safety. 2019;18(9):829–840.