Does taking too many medications affect the health of people with HIV?

— Some people take medicines to prevent or treat conditions such as diabetes and heart disease
— A study found that taking many medications (polypharmacy) is linked to an increased risk of falls
— Researchers call for a focus on identifying and managing polypharmacy in people with HIV

Modern HIV treatment (antiretroviral therapy, ART) is highly effective and generally safe. When used as directed, ART suppresses the amount of HIV in the blood (viral load) so that it gradually reaches very low levels (commonly called “undetectable”). This suppression of HIV allows the immune system to repair much of the injury caused by HIV. The power of ART is so tremendous that scientists increasingly project that many ART users will have a near-normal life expectancy. What’s more, well-designed studies in the past decade have found that people whose HIV is undetectable (thanks to consistent ART use) do not pass on the virus to their sexual partners.

However, despite these benefits, ART does not resolve every HIV-related issue. Residual amounts of HIV remain deep within parts of the body, such as the brain, spleen and lymph nodes. The residual HIV may be partially responsible for excess levels of inflammation and immune activation.

Research with HIV-negative people suggests that prolonged and excess inflammation contributes to an increased risk for the following issues:

• cancer
• cardiovascular disease
• depression
• degenerative brain conditions
• fat accumulation in and around the liver
• high levels of cholesterol
• thinning of bones
• kidney injury
• gradual loss of muscle tissue
• lung disease
• premature aging of the immune system

By taking ART and suppressing HIV, levels of inflammation and immune activation decrease significantly. However, they do not fall to levels seen in healthy people without HIV. It is possible that chronic excess inflammation in people who use ART can contribute to an increased risk for the above-mentioned issues.

Aging

Many of the conditions previously listed are also generally associated with aging. As people grow older, they are at higher risk for these conditions. To help people maintain or improve their health and quality of life, doctors prescribe medicines to help manage many chronic conditions, and the number of medicines that people take increases.

The simultaneous use of multiple medicines is called “polypharmacy.”

Aging, HIV and polypharmacy

When someone with HIV also has another medical condition, this is called a “comorbidity.” Studies have found that, in general, as people with HIV age, they tend to develop more aging-related comorbidities than people without HIV. As a result, older people with HIV tend to be taking more medicines (apart from HIV treatment) for chronic conditions than people without HIV of a similar age or than younger people with HIV.

Risks of polypharmacy

Among people with HIV, research has linked polypharmacy to an increased risk for side effects, falls, and problems thinking clearly and with memory. In at least one study, polypharmacy in this population has been linked to an increased risk of hospitalization. Some studies in people with HIV have found that polypharmacy is associated with reduced physical functioning, including slower walking speed.

A recent study

A large study with the U.S. AIDS Clinical Trials Group (ACTG) recently assessed the impact of polypharmacy (in this case, multiple simultaneous medicines other than ART) and what they called “hyper-polypharmacy” (in this case, simultaneous use of 10 or more prescription medicines other than ART). The researchers focused on the impact of different degrees of polypharmacy on walking speed and falls.

A major strength of the ACTG study was that all participants had a suppressed viral load. This is important because people with unsuppressed HIV can have high levels of inflammation and immune activation. These effects of untreated HIV can degrade the health of people with HIV, leading to an increased risk of problems, including frailty over the long-term.

Study details

Researchers enrolled 977 people with HIV. A brief average profile of participants upon study entry was as follows:

• age – most participants (84%) were between 40 and 59 years
• 81% were male and 19% were female at birth
• major ethno-racial groups: White – 65%; people of colour – 35%
• current CD4+ count – 630 cells/mm³
• lowest-ever CD4+ count – 197 cells/mm³
• major co-existing health conditions: peripheral neuropathy – 40%; diabetes – 12%; kidney disease – 10%; cardiovascular disease – 6%
• current tobacco use – 26%
• current substance use (excluding tobacco) – 21%

Participants underwent regular assessments every six months.

Results

Researchers found that the distribution of different degrees of polypharmacy was as follows:

• polypharmacy – 24% of participants were prescribed five or more non-ART medicines
• hyper-polypharmacy – 4% of participants were prescribed 10 or more non-ART medicines

Not surprisingly, researchers found that polypharmacy increased with age. For instance, among people aged 60 and older, 35% were prescribed five or more non-ART medicines. Among people younger than 60, 22% were prescribed five or more non-ART medicines.

Although the number of co-existing health conditions was similar between women and men, the researchers found that women were more likely to experience polypharmacy.

When researchers assessed specific classes of drugs, they stated that “women reported higher prescription opioid use (16%) compared to men (8%).” Proportionally, more women were prescribed hormones than men, presumably because of menopause.

Potentially inappropriate medicines

The researchers estimate that about 81% of participants aged 65 and older were taking at least one inappropriate non-ART medicine. This requires further investigation with the patients’ medical teams to be certain.

Polypharmacy and walking speed

According to the researchers, “40% of participants exhibited slow [walking] speed.” Participants with a slow walking speed were more likely to be:

• Hispanic
• on public health insurance
• women
• aged 55 and older

When researchers took many factors into account (such as age, sex, race/ethnicity, education level, CD4+ count and so on), they found that polypharmacy was significantly linked to an increased risk for slow walking speed.

When researchers further analyzed the data and considered the number of ART medicines, the presence of hyper-polypharmacy increased the likelihood of slow walking.

Falls

During the study, 12% of participants reported falling at least once and 5% reported falling twice or more.

About 4% of participants who fell broke their bones.

Falls were more likely in people who were:

• aged 55 and older
• women
• Hispanic
• on public insurance

Researchers found that polypharmacy doubled the risk of recurrent falls. Hyper-polypharmacy increased the risk of falls almost fivefold.

When researchers included ART in their analysis on falls, the effects of polypharmacy and hyper-polypharmacy remained the same (as above).

Bear in mind

As the researchers were able to take into account participants’ ages and different health conditions and so on, they were able to focus on the likely effect of the burden of non-HIV medicines on walking speed and falls.

The researchers encouraged clinicians to uncover and reduce the risk of polypharmacy.

The researchers noted that other studies have found a connection between socioeconomic status, low levels of education and polypharmacy. According to the researchers, this connection can arise because of “poor care coordination among populations of low socioeconomic status.” The researchers did not have data on income, but perhaps reliance on public health insurance could reflect lower socioeconomic status in the present study.

The researchers did not have data on the mental health of participants. A future study needs to explore why women (at least in this study) were prescribed more non-ART medicines than men. The research team suspects that mental health issues may have contributed to the need for polypharmacy in some women.

The researchers stated that, overall, their results “suggest that there may be a need for increased attention to medication management among people with HIV, particularly among women and older individuals. This could include efforts to reduce polypharmacy and inappropriate medication use and increased monitoring for drug-drug interactions.”

Additionally, the researchers stated that “the finding that polypharmacy was associated with higher odds of slow [walking speed] suggests that polypharmacy may have negative impacts on physical functioning among people with HIV.”

A note about why polypharmacy may have occurred

Note that some people with complex conditions—particularly those who have survived complications from a heart attack or stroke or who have a transplanted organ—may need to take many different medicines as doctors seek to keep them alive and healthy over the long term. In such cases, polypharmacy is medically necessary. However, it is always a good idea for people to periodically check with their medical team about the appropriateness of non-ART medicines and whether they need to make changes to their prescription.

Also, some people who have HIV that is wholly or partially resistant to treatment may need to take complex combinations of ART. This can involve many pills. Although simplified yet powerful HIV treatment regimens with a reduced number of drugs have been approved, these combinations may not always be suitable for everyone with multidrug-resistant HIV. Examples of simplified HIV treatment regimens include Dovato (an oral combination of dolutegravir + 3TC) and Cabenuva (an injectable combination of cabotegravir + rilpivirine).

An experimental combination of two other anti-HIV drugs – lenacapavir + bictegravir – is in clinical trials.

Thus, for people with multiple comorbidities and/or HIV with complex patterns of resistance, polypharmacy may be necessary. However, monitoring is required to ensure that polypharmacy does not add to the risk of further problems.

For the future

The researchers encouraged the development and testing of interventions that they said would be “aimed at reducing polypharmacy and inappropriate medication use.”

By Sean R. Hosein

Resources:

Canadian study explores the impact of aging on people with HIV – CATIE News

French researchers study frailty in older people with HIV – CATIE News

American researchers explore a link between comorbidities and frailty in HIV – CATIE News

Study uncovers health issues and concerns of some aging HIV-positive people – CATIE News

Large study confirms near-normal life expectancy for many people on HIV treatment – CATIE News

REFERENCES:

1. Kosana P, Wu K, Tassiopoulos K, et al. Polypharmacy is associated with slow gait speed and recurrent falls in older people with HIV. Clinical Infectious Diseases. 2024 Jun 14;78(6):1608-1616.
2. Dufour C, Ruiz MJ, Pagliuzza A, et al. Near full-length HIV sequencing in multiple tissues collected postmortem reveals shared clonal expansions across distinct reservoirs during ART. Cell Reports. 2023 Sep 26;42(9):113053.
3. Mohammadzadeh N, Roda W, Branton WG, et al. Lentiviral infections persist in brain despite effective antiretroviral therapy and neuroimmune activation. mBio. 2021 Dec 21;12(6):e0278421.
4. McMyn NF, Varriale J, Fray EJ, et al. The latent reservoir of inducible, infectious HIV-1 does not decrease despite decades of antiretroviral therapy. Journal of Clinical Investigation. 2023 Sep 1;133(17):e171554.
5. Cadena AM, Ventura JD, Abbink P, et al. Persistence of viral RNA in lymph nodes in ART-suppressed SIV/SHIV-infected Rhesus Macaques. Nature Communications. 2021 Mar 5;12(1):1474.
6. Obare LM, Temu T, Mallal SA, et al. Inflammation in HIV and its impact on atherosclerotic cardiovascular disease. Circulation Research. 2024 May 24;134(11):1515-1545.
7. Baechle JJ, Chen N, Makhijani P, et al. Chronic inflammation and the hallmarks of aging. Molecular Metabolism. 2023 Aug; 74:101755.
8. Lopez Angel CJ, Pham EA, Du H, et al. Signatures of immune dysfunction in HIV and HCV infection share features with chronic inflammation in aging and persist after viral reduction or elimination. Proceedings of the National Academy of Sciences USA. 2021 Apr 6;118(14):e2022928118.
9. Furman D, Campisi J, Verdin E, et al. Chronic inflammation in the etiology of disease across the life span. Nature Medicine. 2019 Dec;25(12):1822-1832.