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CATIE
  • Frailty is more common among people living with HIV than their HIV-negative peers
  • A Dutch study found abdominal obesity, co-morbidities and depression may play a role
  • Researchers noted that the factors driving frailty are preventable and reversible

Potent combination HIV treatment (ART) has had a tremendous impact on the HIV epidemic. Research suggests that many ART users will have a near-normal life expectancy. Not surprisingly, more and more HIV-positive people in North America and Western Europe are living longer and many are now over the age of 50.

As all people age, they can develop health conditions, called comorbidities, such as higher-than-normal blood pressure, abnormalities of blood sugar and cholesterol, kidney injury and thinning bones. Over the long-term, these comorbidities and perhaps other factors likely contribute to an increased risk for poor health, falls, hospitalization, disability and reduced life expectancy.

Research suggests that HIV infection can accelerate the aging process but that this acceleration can be significantly reduced by initiating and continuing to take ART. However, because many people are not immediately aware of the timing of their infection, there is a delay in initiating ART. This delay can last for months or years. During the time not spent on ART, the aging process is accelerated and this acceleration may increase the future risk for the development of comorbidities.

Aging in Amsterdam

Researchers in Amsterdam have recruited a group of HIV-positive and HIV-negative people of similar socio-demographic background. These participants are in a study on aging called AGEhIV.

The researchers have produced useful reports about aging and HIV in the past. In their latest analysis, the researchers found that HIV-positive people are at heightened risk for developing some degree of frailty. This risk was influenced by factors such as abdominal obesity, total number of comorbidities and symptoms of depression. Studies are needed to determine whether intervening against these factors can reduce the risk of frailty in HIV-positive people.

About frailty

Frailty was assessed during study visits and focused on the following issues:

  • unintentional weight loss
  • low levels of physical activity
  • exhaustion
  • decreased hand grip strength
  • slower-than-normal walking speed

Researchers used the data gathered from the assessments to grade each person. They then gave the participants a frailty score and divided them based on this score into the following groups:

  • robust
  • pre-frail
  • frail

Researchers analysed health-related information from 497 HIV-positive people and 479 HIV-negative people who were monitored between October 2010 and October 2016. The average profile of HIV-positive participants upon study entry was as follows:

  • age – 53 years
  • 89% men (75% of whom were gay or bisexual), 11% women
  • major ethno-racial groups: White – 90%; people of colour – 10%
  • current smoker – 32%
  • comorbidities: none – 48%; one – 31%; two or more – 21%
  • frailty distribution: robust – 37%; pre-frail – 52%; frail – 11%
  • CD4+ count – 565 cells/mm3
  • history of AIDS – 32%
  • proportion on ART – 95%
  • proportion with a suppressed viral load – 95%
  • duration of HIV infection – 12 years

Results

According to the researchers, the distribution of frailty status was as follows:

Robust
HIV-positive people – 37%
HIV-negative people – 61%

Pre-frail
HIV-positive people – 52%
HIV-negative people – 36%

Frail
HIV-positive people – 11%
HIV-negative people – 3%

Thus, overall, HIV-positive people were in generally weaker physical condition.

Frailty transitions

Over the course of the study, the researchers found that 37% of HIV-positive people remained in a robust state of health. However, the remaining HIV-positive people could be divided into the following two groups:

Moving toward frailty – 46%
People in this group moved from robust to pre-frail or from pre-frail to frail.

Moving towards robustness – 54%
People in this group moved from frail to pre-frail or from pre-frail to robust.

During the study, the researchers found that most transitions occurred in either direction between robust and pre-frail states. It was rare for people to move directly from robust to frail and vice versa.

In total, there were 38 deaths distributed as follows:

  • HIV-positive people – 5% died
  • HIV-negative people – 1% died

Causes of death (and hospitalizations) were not provided.

Factors influencing the transition to frailty

Among HIV-positive people, the following factors played a role in the transition toward frailty:

  • abdominal obesity
  • greater number of comorbidities
  • having symptoms of depression

Taking advantage of the dynamism of frailty transitions

The HIV-positive people in the Dutch study represent what researchers called “a highly treatment-experienced population…with a prolonged duration of HIV infection, lengthy exposure to ART and excellent levels of viral suppression.” They stated that several factors influence the risk for frailty and that “frailty is one end of the spectrum of what is a highly transitional phenotype.” In other words, the frailty transition is dynamic; it can move first in one direction and then another.

The researchers noted that the drivers of frailty in their study—abdominal obesity, the number of comorbidities, symptoms of depression—are “potentially preventable and reversible, and thus deserving of attention as part of routine HIV care.” The researchers encouraged doctors and nurses to pay “proper attention to symptoms of depression in the care of [HIV-positive people], not only to improve mental health but potentially also to help ensure current and future physical health.”

The researchers pointed out that a review of studies done with HIV-negative people suggests that “increasing the level of physical activity significantly reduced frailty.” It is at least plausible that a similar intervention with HIV-positive people could have beneficial results. However, clinical trials are needed to study and fine-tune interventions to enhance the health and well-being of HIV-positive people.

–Sean R. Hosein

Resources

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

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

Factors linked to falling in middle-aged womenTreatmentUpdate 218

Exercise as medicineTreatmentUpdate 234

Study finds fat goes up, muscle goes down over time – TreatmentUpdate 235

REFERENCES:

  1. Verheij E, Wit FW, Verboeket SO, et al. Frequency, risk factors and mediators of frailty transitions during long-term follow-up among people with HIV and HIV-negative AGEhIV cohort participants. JAIDS. 2020; in press.
  2. Sehl ME, Rickabaugh TM, Shih R, et al. The effects of anti-retroviral therapy on epigenetic age acceleration observed in HIV-1-infected adults. Pathogens and Immunity. 2020; in press.
  3. Guaraldi G, De Francesco D, Milic J, Franconi I, Mussini C, Falutz J, Cesari M. The interplay between age and frailty in people living with HIV: Results from an 11-year follow-up observational study. Open Forum Infectious Diseases. 2019 May 17;6(5):ofz199.