- A large Canadian study reviewed pharmacy prescription data from 19,000 people with HIV
- Analysis of data between 2010 and 2020 found that nearly half had less-than-ideal adherence
- The researchers call for studies to better understand the factors driving non-adherence
When used as directed, HIV treatment (ART) can reduce levels of HIV in the blood. Over time, with continued medication-taking, HIV levels become suppressed in the vast majority of ART users. This low level of HIV is commonly called “undetectable.”
By keeping HIV suppressed with good adherence, the immune system is able to repair itself. As a result, the risk of AIDS-related infections becomes extremely low. The power of ART is so tremendous that researchers expect many ART users to have near-normal life expectancy.
However, some people with HIV struggle with periods of anxiety and depression, addiction, insufficient food, violence and homelessness. These and other factors can affect a person’s ability to adhere to their treatment regimen (take their medicine as directed) and maintain a suppressed viral load.
A team of researchers in Canada reviewed information collected from databases about the timeliness of filling—and refilling—prescriptions for ART in more than 19,000 people with HIV. Analysing prescription-filling data can provide a crude estimate of adherence and has been validated by researchers in British Columbia over the past two decades.
In the Canadian study, the researchers found that 45% of ART users did not fill their prescriptions on time (causing gaps in their supply of medicine) and therefore underwent periods when they were not on treatment.
Statistical analysis found that people who had reduced adherence were more likely to be younger and were more likely to be on regimens that required them to take multiple tablets each day.
The analysis of pharmacy refill data may be imperfect. However, its key findings that subgroups of people had reduced adherence is likely true and aligns with data from other studies. For instance, previous studies in different countries have found that younger people are more likely to have difficulty with adherence than older people. Other studies in the United States have found that people taking an entire regimen in one pill once daily have better adherence than people taking regimens that consist of multiple pills.
Non-adherence can have many consequences, from treatment failure to the development of HIV that is resistant to one or more therapies to declining health and, in some cases, reduced chances of survival. While the Canadian study did not delve into these consequences, it raises the issue that the drivers of non-adherence need to be studied and that interventions are needed to help people get back on regular medication-taking. If patients do not receive adherence support, the life-prolonging benefits of ART cannot be equitably realized.
The data from Canada on non-adherence are in broad alignment with a study of more than 200,000 people with HIV from the U.S. In that study, researchers found higher-than-expected rates of non-adherence. Details on the U.S. study appear later in this CATIE News bulletin.
Study details
The Canadian researchers focused on several databases, including the following:
- National Prescription Drug Utilization Information System (NPDUIS); in several provinces)
- Régie de l’assurance maladie du Quebec (RAMQ); in Quebec)
- Pharmaceutical Information Network (PIN); in Alberta)
Researchers were able to get information on ART use and prescription refills from the following provinces:
- Alberta
- Saskatchewan
- Manitoba
- Ontario
- Quebec
- New Brunswick
- Newfoundland and Labrador
The researchers were able to estimate the days that participants did not have ART (on such days, participants were classed as non-adherent) based on the information from pharmacy databases. The greater the number of days without ART, the greater the degree of non-adherence that the researchers attributed to participants.
All participants were adults, and most were male (74%). Most were 35 to 64 years old; 25% were younger than 35 years old.
In addition to ART, some participants took medicines prescribed for the following conditions:
- depression
- sleeping problems
- high blood pressure
- abnormal lipid levels in the blood
The researchers reviewed data collected between 2010 and 2020.
Results
Researchers found that 55% of participants refilled their prescriptions in a timely manner. These participants were described as having 95% adherence or greater.
Researchers divided the remaining participants based on their estimated adherence, as follows:
- 90%-94% adherence – 20% of participants
- 85%-89% adherence – 10% of participants
- 80%-84% adherence – 6% of participants
- 60%-79% adherence – 8% of participants
- 40%-59% adherence – 1% of participants
Factors linked to non-adherence
Statistical analysis revealed that, overall, people who did not refill their prescriptions on time were more likely to be younger and/or taking multi-tablet regimens.
In an analysis restricted to three provinces (Alberta, Saskatchewan and Manitoba) whose databases had extensive information available on non-HIV-related medication usage, researchers found that participants who were also prescribed medicines for the following conditions were likely to have less-than-ideal adherence to HIV medicines:
- substance use disorder
- high cholesterol
- diabetes
Other analyses of the data from these three provinces suggested that the following factors were also linked to reduced adherence to HIV medicines:
- being female
- being younger
- having co-existing health conditions (comorbidities)
Bear in mind
This Canadian study should be seen as a good first step toward exploring ART adherence across a large population. Adherence is a complex, dynamic behaviour that is difficult to study. Filling a prescription does not necessarily mean that people took all or some of their pills.
Furthermore, researchers were not able to access information on medical history, laboratory test results (such as viral load) and clinical outcomes (such as infections and deaths).
However, previous studies done in British Columbia over the past 20 years have linked poor adherence with a greater likelihood of unsuppressed viral load, subsequent poor health and, in some cases, reduced life expectancy.
In the present study, participants were not interviewed, so their reasons for apparent non-adherence cannot be certain.
However, what is clear from the study is that regimens that require multiple pills are associated with reduced adherence in some people. Many studies of people with HIV in the United States have confirmed that adherence is easier with single-tablet regimens.
A previous study in Alberta asked participants with HIV about reasons for non-adherence. Researchers involved with that study stated: “The primary cause given for poor adherence was difficulty remembering followed by inconvenient dosing schedule and difficulty scheduling [medication-taking] times around meals.”
Today in Canada (and other high-income countries), leading regimens of powerful and generally well-tolerated combinations of drugs are available in one pill, including the following:
- Biktarvy – bictegravir + TAF + FTC
- Dovato – dolutegravir + 3TC
- Delstrigo – doravirine + 3TC + TDF
- Triumeq – dolutegravir + 3TC + abacavir
Furthermore, a long-acting regimen called Cabenuva, which consists of injectable formulations of the drugs cabotegravir + rilpivirine, has been approved for several years. Ultimately, Cabenuva can be injected every month or every two months.
Keep in mind that the one-pill regimens and injectable drugs listed above were not available at the start of the period studied (2010). Also, many of the regimens available now are likely better tolerated than the regimens that were in widespread use in 2010 and for a few years after. It is plausible that some patients back then took unsupervised breaks from their treatment because of the toxicity of earlier regimens. However, this issue was not explored in the present study.
It is possible that a subset of patients today who are still taking multi-tablet regimens or older regimens could benefit from switching to a single-tablet regimen consisting of newer drugs or to injectable ART.
More research on non-adherence is needed in Canada so that healthcare providers can support the needs of patients and help them achieve and maintain better health.
In the United States
In a U.S. study with more than 200,000 people with HIV, researchers focused on the period of July 2017 to September 2018. Participants were from every state. The researchers also reviewed pharmacy refill records and found that more than 60% of participants had less than 90% adherence. These participants did not appear to be filling their prescriptions on time and went for periods without HIV treatment. As the study was simply based on pharmacy records, the researchers are not certain why non-adherence occurred. Also, the study looked back on data that was collected for one purpose and then reanalysed for another. Such a retrospective analysis may have over-estimated adherence, particularly as data about the taking of pills was not able to be collected.
As mentioned earlier, non-adherence can have consequences for patients, including the development of HIV that is partially or wholly resistant to some treatments. Another team of researchers in the U.S. explored the issue of non-adherence and found that rates of resistance to treatment varied between 20% and 54%, depending on the state. What’s more, the same team found that states with the highest levels of HIV drug resistance tended to have people with HIV who as a group had poor rates of adherence to treatment.
The data from Canada and the U.S. are in broad alignment. Together the data strongly suggest that more work is needed to understand the drivers of non-adherence. Such work should include interviews with patients, so that effective interventions can be developed to help people take their pills (or injections) on a regular basis.
—Sean R. Hosein
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