Effective antiretroviral therapy (ART) is enabling people with HIV infection to live longer. As a result, the HIV-related morbidity experienced by this aging population is shifting from illness caused by opportunistic infections to illness caused by chronic, non-communicable cardiovascular, kidney, and liver diseases. This population is also subject to frailty, an age-related cognitive and functional decline that can decrease a person's physiological reserve and increase vulnerability to external stressors.
Characteristics associated with frailty: In the HIV-related peer-reviewed literature, frailty is often defined as the presence of 3 or more of the following 5 characteristics: unintentional weight loss, exhaustion, weakness, low physical activity, and slowed walking speed. Frailty increases the risk of falls, hospitalizations, and death; thus, it is the subject of increasing research and clinical attention.
A recently published study by Erlandson and colleagues [
J Infect Dis, 2017 Mar 15;215(6)
] sought to identify modifiable risk factors for frailty in patients taking ART. The researchers analyzed the frailty assessments of 1,016 participants from the ACTG A5322 observational cohort study, which had recruited participants from prior ACTG studies. All participants were aged ≥40 years, and 85% were aged <60 years; 19% were females;
and 48% were White non-Hispanic, 30% were Black non-Hispanic, and 20% were Hispanic
. Upon study entry, participants' frailty was assessed as follows:
- Walking speed and grip strength: Observation
- Weight loss: Self-report
- Low physical activity and exhaustion: Quality of life scales
- Demographics, economic status, and medical characteristics: Historical study data
Of all study participants, 6% met criteria for frailty, and 38% were pre-frail (had 1 or 2 of the 5 frailty components). Risk factors associated with frailty included the following:
- Female sex
- Receiving Medicaid or Medicare benefits
- Older age
- Less education
- Lower physical activity
- HCV antibody positivity
- Neurocognitive impairment
ART associated with frailty? Efavirenz use appeared to increase risk of frailty in the overall analysis, but not in an analysis limited to participants whose initial regimen had been randomized to efavirenz or atazanavir in a prior study (ACTG 5202). Integrase strand transfer inhibitors (INSTIs) had a stronger association with a non-frail state. The authors argue, and I agree, that the findings regarding specific ART agents and frailty should be interpreted with caution because this is not a randomized clinical trial. It is an observational study, and multiple factors may have influenced ART selection. In addition, INSTIs are a newer class of antiretroviral drugs and may reflect changes in care or participant characteristics over time.
Risks: What was most striking in this study is that many of the factors associated with increased risk of frailty represented structural inequality, such as being a recipient of public health benefits or having less than a high school education. Moreover, factors that are often associated with structural inequality were also associated with increased frailty: female sex, race other than White, poverty, smoking, and obesity.
These results suggests that preventing frailty may require far more than choosing ART regimens carefully. That said, it's clear that more studies are needed to better understand how to address frailty and pre-frailty once those conditions are identified.