Middle-aged people living with HIV have an increased risk of frailty

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Middle-aged people living with HIV have an increased risk of frailty compared with their peers without the virus, Dutch investigators report in AIDS. The association between frailty and HIV infection persisted even after taking into account well-known risk factors for the condition.

“We investigated the frailty phenotype in a population of middle-aged HIV-infected individuals, predominately with undetectable HIV viral load on cART [combination antiretroviral therapy], and similar HIV-uninfected controls,” explain the authors. “Depression, low BMI and higher WHR [waist-to-hip ratio] were strongly associated with a higher frailty category, but none of the investigated factors could fully explain the observed association between HIV infection, prefrailty, and frailty.” Low body mass index [BMI] was especially associated with frailty in people with HIV.

Frailty begins to show itself in the forms of weight loss, slowed walking pace, reduce grip strength, exhaustion and a consequent decline in physical activity.



Describes a general decline in physical health and a loss of reserves, most often seen in older people. Frailty leads to a person being less robust and less able to bounce back after an adverse event. A person with frailty may move more slowly, have lost some of their physical strength, have less energy and be less mentally agile. 

body mass index (BMI)

Body mass index, or BMI, is a measure of body size. It combines a person's weight with their height. The BMI gives an idea of whether a person has the correct weight for their height. Below 18.5 is considered underweight; between 18.5 and 25 is normal; between 25 and 30 is overweight; and over 30 is obese. Many BMI calculators can be found on the internet.


A mental health problem causing long-lasting low mood that interferes with everyday life.


In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 


Lowest of a series of measurements. For example, an individual’s CD4 nadir is their lowest ever measured CD4 count.

Frailty is a medical syndrome with multiple possible causes. Regardless of the cause, it is associated with increased risk of illness and death. A higher prevalence of frailty has been observed in people with HIV when compared to matched HIV-negative controls. The inflammatory effects of HIV infection, HIV-related illness and the side-effects of some antiretroviral drugs have been suggested possible reasons for the association between frailty and HIV.

Investigators from the Dutch AGEh IV Cohort Study wanted to clarify the association between HIV infection and frailty and prefrailty (a milder, possibly reversible form of frailty). They designed a study involving 521 HIV-positive people and 513 closely matched HIV-negative controls. All were aged 45 years or older at baseline. Recruitment occurred between 2010 and 2012.

All participants were assessed for frailty/prefrailty using the criteria established by Fried and colleagues. This assessment involves assessment of five domains:

  • unintentional weight loss exceeding 4.5kg in the previous year or 2.3kg in the previous six months

  • low physical activity

  • exhaustion

  • low maximum grip strength

  • slow walking speed.

People were diagnosed with frailty if at least three criteria were present; prefrailty was the presence of one or two domains.

Data were also gathered on the presence of non-HIV-related and HIV-related factors possibly related to frailty/prefrailty.

Participants had an average age of 53 years. People with HIV were more likely than the controls to have hepatitis C virus infection, depression and co-morbid illnesses. The people with HIV had been diagnosed for an average of twelve years, 94% were taking HIV therapy and 93% of these had an undetectable viral load.

People with HIV were significantly more likely to be frail (11% vs. 3%) or prefrail (51% vs. 36%) than HIV-negative controls (p < 0.001). This was true for all age categories.

The association between HIV infection and frailty was significant after adjustment for age, sex, race/ethnicity, smoking, hepatitis C virus infection, the presence of co-morbidities and depression (adjusted OR, 2.16; 95% CI, 1.66-2.83, p < 0.001).

Taking into account waist-to-hip ratio weakened the association between HIV infection and frailty though this remained significant (adjusted OR, 1.93; 95% CI, 1.46-2.55; p < 0.001). BMI also attenuated the association between HIV infection and frailty (adjusted OR, 1.74; 95% CI, 1.31-2.32, p < 0.001).

HIV-positive people with a BMI below 20kg/m2 had a more than six-fold increase in the risk of frailty compared to HIV-positive people with higher BMI (OR, 6.14; 95% CI, 3.10-12.18, p < 0.001).

An analysis that involved only people with HIV showed that longer duration of protease inhibitor therapy (OR, 1.05/year; 95% CI, 1.01-1.10, p = 0.01) and longer duration of immune suppression (OR, 1.14/year; 95% CI, 1.00-1.30, p = 0.05) were associated with frailty. But after adjustment for current and nadir BMI below 20kg/m2 both these factors ceased to be significant. After controlling for potential confounders, a current BMI below 20kg/m2 (OR, 2.83; 95% CI, 1.26-6.37, p = 0.01), a nadir BMI less than 20kg/m2 (OR, 2.51; 95% CI, 1.46-4.31, p = 0.001) and waist-to-hip ratio (OR 1.79 per 0.1 higher; 95% CI, 1.32-2.41, p < 0.001) were all strongly associated with frailty.

“Frailty may be a long-term consequence of having experienced advanced HIV disease,” conclude the authors. “The observed association between greater WHR and a higher frailty category, which in part explained the association between HIV-infection and frailty, thus suggests that body composition changes may also have contributed to the onset of frailty.”


Kooij KW et al. HIV infection is independently associated with frailty in middle-aged HIV type 1-infected individuals compared with similar but uninfected controls. AIDS 30: 241-250, 2016.