Frailty, Nerve Injury and Falls in Middle-Aged and Older HIV-Positive People

September 13, 2017

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More HIV-positive people are living longer thanks to the use of potent combination anti-HIV therapy (ART). As HIV-positive people enter their middle age and senior years, they will have to grapple with one or more aging-related issues. One issue that can have a large impact on the health and quality of life of older people is falling. Older people who fall can injure themselves, and according to U.S. researchers, such injuries can make pre-existing problems, such as physical inactivity or weakness, worse.

Some studies with middle-aged and older HIV-positive people suggest that being frail and physically impaired are relatively common. One study found that HIV-positive adults whose average age was 52 years were at a similar risk of falling as HIV-negative adults 65 years or older.

The Present Study

In a U.S. study code-named ACTG A5322 researchers enrolled more than 900 middle-aged and older HIV-positive people to study their health. One report that emerged from this research concerns frailty and falling. The researchers found that frailty was uncommon, occurring in 6% of participants. However, nearly 40% of participants were becoming physically weaker and labelled as "pre-frail" by the researchers.

Statistical analysis found that people who were frail or pre-frail were at increased risk of falling. People who were frail and had injured nerves in their feet/legs (peripheral neuropathy) were also at elevated risk for falling.

The study underscores one aspect of aging and that some HIV-positive people, even in middle age, will need screening for factors linked to an increased risk for falls.

Study Details


Researchers enrolled participants from across the U.S. between November 2013 and July 2014. Participants visited study clinics every six months where they were interviewed, completed questionnaires, underwent a physical exam and had blood drawn for analysis. Participants were also assessed for the presence of co-existing health conditions and, in particular, neurocognitive problems.

On average, participants were in their mid-50s; 80% of participants were men and 20% were women.

Researchers defined falls as "an unexpected event in which the individual loses their balance and lands on the floor, ground or at a lower level and/or hits an object." The researchers did not count falls that occurred because of a stroke or because a person was pushed or shoved.

The researchers used a validated method of assessing frailty that included the following:

  • the strength of a person's grip (using a dynamometer)
  • how fast or slow they walked for a distance of four metres (this is called gait speed)
  • self-reported unintentional weight loss
  • self-reported exhaustion
  • self-reported limitations in various physical activities

Results -- Falls

Researchers analysed data collected from 967 people and found that 174 people (18%) had at least one fall in the past year. The distribution of falls was as follows:

  • 106 people (11%) -- one fall in the past year
  • 68 people (7%) -- more than one fall in the past year

Among the 174 people who fell, 21% sought medical help as a result of falling. About 5% were found to have at least one broken bone.


After assessing all study participants for frailty, here is what the researchers found:

  • 55% were non-frail
  • 39% were pre-frail
  • 6% were frail

The distribution of frailty and falls was as follows:

  • among non-frail people -- 12% fell at least once in the past year
  • among pre-frail people -- 22% fell at least once in the past year
  • among frail people -- 49% fell at least once in the past year

Researchers found that participants with weak grip strength were more likely to have recurring falls than people without weak grip strength.

Also, participants who walked slowly were more likely to have had recurrent falls than people who walked at a normal pace.

Peripheral Neuropathy (PN)

People with HIV can develop injured nerves in their feet, legs and hands. There are many reasons PN can occur, including the following:

  • HIV-related reasons: Experiments with monkeys infected with a virus closely related to HIV called SIV (simian immunodeficiency virus) have found that monkeys can develop nerve injury because of proteins produced by SIV-infected cells. So it is very likely that proteins produced by HIV-infected cells can cause inflammation and injury in susceptible nerve cells, leading to PN in people with HIV. Furthermore, some studies have found that high viral loads are associated with an increased risk for PN.
  • past use of one or more of a group of older anti-HIV drugs called "D-drugs" -- ddC (zalcitabine, Hivid), ddI (didanosine, Videx, Videx EC) and d4T (stavudine, Zerit). Although the use of D-drugs is no longer recommended by treatment guidelines in high-income countries, PN can be a lingering legacy of exposure to this group of medicines.
  • co-infection with a common member of the herpes virus family -- CMV (cytomegalovirus)
  • type 2 diabetes
  • deficiency of vitamin B12
  • excessive exposure to alcohol
  • shingles (herpes zoster)
  • impaired thyroid gland functioning
  • exposure to some antibiotics used for treating TB

After assessing participants, researchers found that 39% (373 people) had PN. Furthermore, the researchers stated that people who were frail and who had PN "were significantly more likely to experience falls than non-frail people."

In general, researchers did not find evidence that other co-existing conditions, including neurocognitive impairment, had any significant impact on frailty and falls.

A previous U.S. study with about 650 HIV-positive women also found a link between the presence of PN and an increased risk of falls.

CATIE's Practical Guide to HIV Drug Side Effects has a section on PN that has useful options to consider.

Points to Consider

This study confirms that HIV-positive people who have some degree of frailty (that is, they were frail or pre-frail) are at increased risk for falling.

Two standardized and measurable aspects of frailty -- strength and slow pace of walking (slow gait speed) -- were significantly linked to an increased risk for falling.

It is possible that the participants in this study may not be reflective of patients that doctors see in clinics. This possibility arises because the researchers stated that many of the people who entered the present study had a history of volunteering for HIV-related clinical trials. Nevertheless, it is possible that some HIV-positive people outside of this study are at increased risk for frailty and falls.

Advice From Researchers

Based on the results of their study, the researchers encourage doctors and nurses to incorporate simple evaluations of frailty, such as grip strength and gait speed, as possible ways of identifying their HIV-positive patients at heightened risk for falling. Patients with this risk can then be given education to help prevent falls. Also, the researchers noted that HIV-positive people with PN might also need screening for their risk for falls.

Bear in Mind

The present study has uncovered two aging-related issues affecting HIV-positive people: frailty and falls. These problems are traditionally seen in elderly HIV-negative people but in the present study they occurred in some middle-aged HIV-positive people.

An Aging Epidemic

Research suggests that by the early 1970s HIV had arrived in North America and its spread eventually led to the appearance of the first recognized cases of AIDS in 1981. HIV-positive people who survived that era are now well over the age of 50.

In several studies, despite the use of ART for many years with excellent adherence, researchers have found that HIV still persists in lymphatic tissues of participants and causes ongoing inflammation and activation of the immune system. This ongoing immune activation and inflammation may make some HIV-positive people more susceptible to aging-related complications. Therefore, researchers need to continue to engage in research with aging HIV-positive people to find ways to help them enter middle and old age with good quality of life.

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This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication CATIE News. Visit CATIE's Web site to find out more about their activities, publications and services.

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