Frailty in men with HIV linked with bone weakness, muscle loss and large waist

Frailty is twice as prevalent in middle-aged and elderly HIV-positive men as in their HIV-negative peers, investigators from the Multicenter AIDS Cohort Study (MACS) report in AIDS. Risk factors were abdominal obesity, loss of skeletal muscle mass (sarcopenia) and osteoporosis and these did not differ by HIV status. Men with HIV with the highest waist measurements were seven times more likely to be living with frailty than men with lower waist measurements.

Assessment of waist circumference during routine care could be an easy way of identifying ageing men at risk of frailty, suggest the investigators.

“We found robust associations between frailty and central adiposity and sarcopenia. To the best of our knowledge, the association between frailty and VAT [visceral adipose tissue] area in adult men with HIV has not been previously reported,” comment the authors.



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. 


Bone disease characterised by a decrease in bone mineral density and bone mass, resulting in an increased risk of fracture (a broken bone).

adjusted odds ratio (AOR)

Comparing one group with another, expresses differences in the odds of something happening. An odds ratio above 1 means something is more likely to happen in the group of interest; an odds ratio below 1 means it is less likely to happen. Similar to ‘relative risk’. 


Pertaining to the internal organs. Visceral fat is fat tissue that is located deep in the abdomen and around internal organs.


bone mineral density (BMD)

The higher your bone mineral content, the denser your bones are. And the denser your bones, the stronger they are and the less likely they are to break. A bone density test uses X-rays to measure how many grams of calcium and other bone minerals are packed into a segment of bone. The bones that are most commonly tested are in the spine, hip and sometimes the forearm. 

“Underlying mechanisms that link central adiposity, sarcopenia, and frailty are likely due, in part, to chronic levels of underlying inflammation and immune activation.”

Frailty is associated with adverse outcomes, especially in the elderly. Many HIV-positive people are now living into older age and have multiple risk factors for frailty such as treatment side-effects and lifestyle factors such as smoking.

In practical terms, living with frailty means a reduced ability to carry out everyday tasks and care for oneself due to lower energy and strength. People who are living with frailty have reduced reserves to deal with the stresses of everyday life, as well as reduced resilience after a shock such as a fall, a comorbid condition or a medical intervention. Specialists in geriatric medicine think of a spectrum of frailty, along which people need differing levels of support.

In the general population, frailty is associated with low muscle mass, low bone mineral density and higher waist-to-hip ratio. The association between body composition and frailty in older HIV-positive men is poorly understood. In particular, it is unclear if central fat accumulation (visceral fat around the organs) – often associated with the lipodystrophy syndrome in HIV infection – plays a role in the development of frailty.

Investigators designed a study to establish the prevalence of frailty in men with and at risk of HIV and to identify whether body composition was associated with frailty.

The study population consisted of 399 men (199 with HIV) who were enrolled in the MACS bone sub-study. The men were aged between 50 and 69 years (median age 60 years). All the HIV-positive men were taking antiretroviral therapy (for a median of 12.5 years) and the median CD4 cell count was 641 cells/mm3.

Multiple characteristics of frailty were assessed, including unintentional weight loss, exhaustion, slow walking speed, low levels of physical activity and weak grip strength.

Assessments of body composition included BMI, waist circumference, visceral adipose tissue, subcutaneous adipose tissue, bone mineral density and sarcopenia.

In assessing the association between HIV and frailty, the investigators took into account possible confounders such as depression, co-infection with viral hepatitis, reduced kidney function and diabetes.

Overall, 16% of HIV-positive and 8% of HIV-negative men were frail. HIV-positive men had a higher prevalence than HIV-negative men of sarcopenia (41% vs 36%), visceral adipose tissue (56% vs 41%) and osteopenia/osteoporosis (16% vs 9%).

HIV infection was associated with a 2.43-fold (95% CI: 1.23-4.79) increase in the risk of frailty.

Frailty was associated with multiple assessments of body composition. Men in the top third of measurements for waist circumference (aOR = 4.18; 95% CI: 1.47-11.9) or increased visceral adipose tissue (aOR = 4.45; 95% CI: 1.41-14.04) were at least four times more likely to have frailty compared to men with lower measurements. Among men with HIV, those in the top third of measurements for waist circumference were seven times more likely to have frailty compared to those with lower measurements (aOR 7.28; 95% CI 1.6-33.21).

An association between these factors and frailty was detected in the entire cohort (p < 0.0001) and also when the analysis was restricted to men with HIV (p < 0.0001).

Sarcopenia (loss of skeletal muscle) had an association with frailty in the entire cohort (aOR = 2.68; 95% CI: 1.11-6.45) and also in HIV-positive men (aOR = 4.08; 95% CI: 1.01-16.41).

Osteoporosis was also identified as a risk factor for frailty (aOR = 13.6; 95% CI: 2.51-73.57) in the cohort overall. A specific association between reduced bone mineral density and frailty in men with HIV fell short of significance, probably because of the low numbers with osteoporosis.

“In this study of nearly 400 men with and without HIV, frailty was associated with HIV infection as well as with central adiposity, sarcopenia and femoral neck osteoporosis,” conclude the investigators. “The high degree of overlap in central adiposity, sarcopenia, and femoral osteoporosis supports the probable existence of a common mechanistic pathway for these conditions; interventions with beneficial effects on all three outcomes may have the greatest potential to prevent, delay, or improve frailty.”


Hawkins KL et al. Abdominal obesity, sarcopenia, and osteoporosis are strongly associated with frailty in MACS. AIDS, online edition, 2018.