Frailty in older HIV positive people: independent associations with serious morbidity and mortality

Simon Collins, HIV i-Base

Frailty is a critical age-related risk that over the last ten years has increasingly been highlighted as an important factor in older people living with HIV. [1, 2, 3] A new analysis from the US MACS by Sean Kelly and colleagues reports independent associations between frailty and cardiovascular disease (CVD), bone disease, diabetes and mortality. [4]

The study included 821 men and 195 women >40 years who were enrolled between 2013-14. Median age was 51 years (IQR: 46 to 56), median CD4 count 621 cells/mm3(IQR: 52 to 827) and 91% had undetectable viral load on ART). Other demographics included 48% white, 29% Black and 23% Hispanic/other, with 39% defined by BMI as overweight and 28% obese.

Frailty was defined as having three or more of the five frailty Fried criteria. [5]

At baseline 62 (6%) of the cohort were defined as frail and 390 (38%) as pre-frail (meeting 1-2 criteria). By week 48, a further 194 participants (19%) progressed to frailty due to changes in the following criteria: weight loss (n=22), low physical activity (n=53), exhaustion (n=72), grip weakness (n=80), and slow gait speed (n=26).

During a median follow-up time of 4.0 years, highest event rates were reported for diabetes and bone disease (see Table 1) both occurring after a median 23 months follow-up.

In adjusted multivariate analysis, baseline frailty was associated with both new onset diabetes and CVD with a trend towards bone events. An increase in frailty from baseline to week 48 was significantly associated with mortality, but was not associated with incident CVD, diabetes, or bone events.  See Table 1. Baseline pre-frailty was not significantly associated with any of the clinical outcomes.

Of the frailty criteria, gait speed, a strong predictor of mortality in older HIV negative adults was most associated with diabetes (p=0.03) and CVD (p=0.06).

Although prevalence of frailty was relatively low at baseline in this population with well-controlled HIV the results support frailty assessment in older HIV positive people.

Frailty can be stopped or reduced by management that includes physical training to increase strength, balance and physical activity. Structured exercise programmes can improve weight, strength, and cardiorespiratory fitness, and reduce the number of frailty criteria.

The study concludes that such interventions are low-risk and, at minimum, may improve health outcomes directly consequent to frailty.

Table 1: Event rates during follow-up

Condition No. events adj. IRR (95%CI) p Med time to event
Diabetes 84 2.29 (1.03 to 5.10) 0.04 23 months
Bone disease 61 2.31 (0.96 to 5.52) 0.06 23 months
CVD 43 3.83 (1.59 to 9.23) 0.003 21 months
Death 27 3.78 (1.52 to 9.39) 0.004 48-week analysis


  1. Desquilbet L 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.
  2. Akgun KMet 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 2014,67:397-404.
  3. Piggott DA et al. Frailty in HIV: epidemiology, biology, measurement, interventions, and research needs. Curr HIV/AIDS Rep. 2016 Dec; 13(6): 340–348. doi: 10.1007/s11904-016-0334-8.
  4. Kelly SG et al. Frailty is an independent risk factor for mortality, cardiovascular disease, bone disease and diabetes among aging adults with HIV.Clinical Infectious Diseases, ciy1101. DOI: 10.1093/cid/ciy1101 (24 December 2018).
  5. Fried LP et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001,56:M146–156.

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