Montreal researchers explore different factors affecting brain health and frailty among older people with HIV

HIV treatment (antiretroviral therapy, ART) is highly effective when used as directed. Increasingly, studies suggest that many ART users will have near-normal life expectancy. However, issues arising from other health conditions become more prominent as people age. These conditions can include diabetes, high levels of cholesterol in the blood, high blood pressure, kidney disease, thinning bones, anxiety, difficulty sleeping and depression. Doctors prescribe medicines (in addition to ART) that are needed by patients with HIV to help manage their non-HIV-related conditions.

Using multiple prescription drugs is called polypharmacy. In many cases, these additional medicines are medically necessary. However, researchers are concerned that some medicines prescribed for non-HIV-related conditions may have an untoward impact on the health of some people with HIV.

In Montreal

A team of researchers at McGill University in Montreal conducted complex statistical analyses based on health-related information from 824 older people with HIV, focusing particularly on the non-HIV-related medicines they were taking. The researchers found that two classes of drugs used by participants—sedatives and a group of drugs that affect acetylcholine (a chemical messenger, or neurotransmitter, used by brain cells and nerves)—could be problematic. Medicines that interfere with this neurotransmitter are called anticholinergic drugs.

The researchers suggest that sedatives and anticholinergic drugs could affect a person’s memory and/or their ability to think clearly, leading to the perception that they are cognitively impaired. This finding that treatments for comorbidities could affect the brain is important because of the history of HIV.

A bit of HIV history

The recognition of the first cases of AIDS occurred in 1981. Then, in 1983, Françoise Barré-Sinoussi, Luc Montagnier and other scientists at the Institut Pasteur in Paris were able to isolate the virus (HIV) that caused AIDS. Shortly after, doctors began to notice that some people with HIV developed cognitive impairment. At first this was puzzling. However, researchers subsequently discovered that untreated HIV infection could degrade the brain and lead to decreased cognitive functioning. In extreme cases, dementia would develop. Thus, it is normal for patients with HIV and their doctors to first suspect that HIV is behind any cognitive issues that develop.

Fortunately, now that effective HIV treatment is widely available in Canada and other high-income countries, HIV-related dementia is extremely rare in people who take ART as directed, maintain a suppressed viral load and continue to visit their healthcare providers regularly and stay on top of emerging health issues.

However, given the history of the virus, when doctors caring for patients with HIV notice decreases in cognition, there can be a concern that it may be related to HIV. The McGill research team suggests that reviewing the medication history of people who perceive their cognitive ability to be declining may be a useful first step in trying to uncover the potential effects of sedatives and drugs with anticholinergic effects. If people are taking such medicines, the researchers state that “reducing the use of anticholinergic and sedative medications could help prevent and manage cognitive impairment in older people living with HIV.”

Study details

Researchers collected health-related information from clinics in Vancouver, Montreal, Hamilton and Toronto. The analysis on polypharmacy relied on data collected from 824 people. Their average profile at their first visit to the study clinic was as follows:

• age – 53 years
• 85% men, 15% women
• years since HIV diagnosis – 17
• lowest-ever CD4+ count – 215 cells/mm³
• current CD4+ count – 610 cells/mm³
• having a detectable viral load – 8%
• having polypharmacy (defined by the researchers as taking five or more non-HIV-related medicines) – 20%
• 12% of participants used the HIV drug efavirenz (in Atripla and Sustiva); in some cases, this drug can affect the brain, causing drowsiness and other issues
• 17% of participants were obese
• 41% of participants took a drug with anticholinergic effects; researchers stated that the anticholinergic burden was high in 13%
• 38% of participants took a sedative; researchers stated that the sedative burden was high in 12%

The researchers also considered additional information to develop their statistical analysis.

Results

The researchers’ statistical analysis led them to conclude that “comorbidities lead to an increase in polypharmacy, which in turn amplifies the effects of anticholinergic and sedative burden. These factors collectively impair cognitive ability and perceived cognitive difficulty and exacerbate physical frailty.”

Furthermore, the researchers also stated that their findings “underscore the interconnected nature of these health factors in people living with HIV, highlighting the necessity for integrated healthcare strategies to address these multifaceted challenges effectively.”

About polypharmacy

The researchers stated that “polypharmacy, often necessary for managing multiple comorbid conditions, significantly affects cognitive ability and physical frailty.”

The researchers stated that the number of (non-HIV) medications is statistically connected to an increased risk for physical frailty. Therefore, they emphasize “the need to focus on personalized, appropriate polypharmacy specific drug classes and interactions, aiming to mitigate adverse impacts on frailty and cognitive decline.”

Impact of depression and anxiety

According to the researchers, participants who had depression and/or anxiety were more likely to perceive cognitive problems (note that sometimes these can be caused by depression and/or anxiety) and have a sense of frailty than people without depression and/or anxiety. The researchers stated that their findings about this connection underscore the need “to address mental health within [HIV] care strategies to improve specific outcomes related to frailty and cognitive function.”

Drug side effects

Sedatives are often used for short-term treatment of sleeping problems. However, some people with chronic sleeping difficulties may use them for longer periods. The drowsiness caused by these drugs may be enhanced by other medicines.

Some drugs used for certain conditions, such as bladder dysfunction, work by exerting their anticholinergic effects. Other drugs are used primarily for their effects on neurotransmitters other than acetylcholine but may cause anticholinergic side effects. This is why consultation with a pharmacist and doctor is important when trying to understand potential drug side effects.

Bear in mind

The McGill study was based on data collected at one point in time. Such studies are good at providing a snapshot of what people are experiencing at one specific point in time. However, some problems may take longer to develop and can wax and wane over time. Funding for a study that monitors participants over the long term would be useful. Such a study could also assess changes in quality of life that people with HIV who have comorbidities experience and how interventions to address comorbidities could improve quality of life.

By Sean R. Hosein

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