- Long-acting injectable HIV treatments are rolling out in Canada and other high-income countries
- A U.S. study with 383 people who wanted long-acting treatment found that 47% didn’t start it
- The main reasons for not starting were missed appointments and difficulty contacting patients
Cabenuva is the name of an injectable HIV treatment that consists of two drugs: cabotegravir + rilpivirine. Cabotegravir is also available in pill form under the name Vocabria, and is taken with Edurant (rilpivirine) also in pill form. The injectable formulation has long-acting activity.
When Cabenuva was initially approved, patients were meant to transition from their current oral regimen to oral formulations of cabotegravir + rilpivirine. These pills are taken once daily. Patients were meant to take these medications orally for several weeks to ensure that they were tolerated before taking the injectable formulation. This is called the oral lead-in period.
If all was well after several weeks on oral lead-in therapy, patients could then begin monthly intramuscular injections for two consecutive months—one injection per buttock (for a total of two injections) per month. After this time, they would only need injections every two months.
The oral lead-in becomes optional
Since the initial approval of Cabenuva, additional data from clinical trials have been released and reviewed by regulatory authorities in Canada and other high-income countries. Based on that data, regulatory authorities have made the oral lead-in therapy optional. Now, patients for whom Cabenuva is suitable can transition from their current oral regimen directly to the long-acting injectable formulation (injections) of Cabenuva, if their doctor agrees.
Cabenuva is a complete treatment and is meant for people whose HIV is suppressed (less than 50 copies/mL or “undetectable”) on their pre-Cabenuva regimen.
Unlike many other HIV regimens, Cabenuva does not suppress hepatitis B virus (HBV). People on Cabenuva who are co-infected with HBV will also need to take medicine to suppress HBV.
Note that Cabenuva is not meant to be used by people who have HIV that is resistant to cabotegravir or rilpivirine.
As Cabenuva ultimately removes the need to take a daily dose of HIV treatment, it is viewed as an attractive option by many people.
In Southern California
A team of researchers at an HIV clinic in San Diego conducted a study to explore issues associated with initiating or not initiating Cabenuva. They scoured the medical records of 383 participants with HIV who had expressed interest in switching from their current oral regimen to long-acting treatment. Data were collected between April 2021 and June 2022.
Among 383 people, 201 (53%) initiated Cabenuva. The researchers found that people who switched treatment to Cabenuva (compared to people who did not) were likely to fit the following profile:
- they were younger
- their pre-Cabenuva regimen consisted of two drugs
Main reasons for not initiating long-acting treatment
The researchers found that the main reasons that people did not initiate Cabenuva were as follows:
- a history of missing clinic/lab appointments
- the clinic staff had difficulty contacting them
Once Cabenuva has been initiated, each series of future appointments has a window of plus or minus seven days within which injections must be given. Maintaining regular appointments once Cabenuva has been initiated is therefore necessary. If these injection appointments are missed, patients may have to switch to oral formulations of Cabenuva for several weeks to minimize the risk of developing HIV that is resistant to cabotegravir and rilpivirine.
A team of researchers from the U.S and Denmark has reviewed studies on missed appointments for HIV care. Commenting on the San Diego study in an editorial in the journal AIDS, they found that, in general, a history of missed clinic appointments is linked to an increased risk for missing future appointments.
The manufacturer of Cabenuva, ViiV Healthcare, states in the treatment’s prescribing information: “Prior to starting Cabenuva, healthcare professionals should carefully select patients who agree to the required injection dosing schedule and counsel patients about the importance of adherence to scheduled dosing visits to help maintain viral suppression, reduce the risk of viral rebound and potential development of resistance with missed doses.”
It is possible, likely even, that with the right comprehensive support and services, patients who have difficulty keeping clinic appointments and lab visits or taking pills daily may welcome the opportunity of starting a long-acting regimen. This has been found in one study in northern California, albeit with a relatively small number of people who were offered a wide array of supportive services. However, such comprehensive support is not common in HIV clinics in Canada and other countries.
Other personal reasons
According to the researchers, other reasons for not initiating Cabenuva involved the following issues:
- not wanting to visit the clinic for injections
- unsure if Cabenuva would work outside of the setting of a clinical trial
- concerns about the pain associated with deep intramuscular injections
The researchers stated that these findings underscore the need to “address the concerns of individuals who may still benefit from [Cabenuva]” so that barriers to its initiation can be removed.
Resistance
As mentioned earlier, Cabenuva is not suitable for people who have HIV that is resistant to either cabotegravir or rilpivirine. In this study, researchers reviewed participants’ HIV resistance testing reports from several years prior. The clinic found that 19% of 135 people who had HIV proviral resistance training, had HIV that was likely resistant to the drugs in Cabenuva. Even though this resistance testing was done several years ago, low-level drug-resistant HIV likely remains within infected cells in lymph nodes or other tissues such as the brain and spleen. Scientists say that such resistance is “archived” (or stored) in HIV-infected cells in the body. In the cases of resistance found by researchers in potential users of Cabenuva in the present study, this was mainly caused by resistance to rilpivirine (as opposed to cabotegravir).
Complex regimens, resistance and age
The researchers found that people who did not initiate long-acting treatment were “more likely” to be taking complex HIV regimens that included a protease inhibitor. Such regimens, they stated, “are more commonly chosen in those with a history of documented or suspected [HIV] drug resistance.”
The researchers speculated that older people were more likely to have HIV that was partially or wholly resistant to the drugs in Cabenuva and were less likely than younger people to initiate it. However, the researchers stated that this possible link between age and HIV resistance is something that needs to be formally evaluated in a future clinical trial.
Other reasons
Researchers analysed data from 182 people who did not initiate Cabenuva. The researchers found that a small proportion of people (8%) who expressed interest in long-acting treatment did not initiate it because when their blood samples were screened by the lab their viral load was found to be detectable.
Another group of people did not give blood samples to the lab for assessing whether their HIV was resistant to the drugs in Cabenuva. As a result, they could not advance in the process of getting long-acting treatment.
Only a small proportion of people had concerns that they would not have insurance coverage for Cabenuva (4%) or could not pay for pharmacy dispensing fees or other costs (3%).
Bear in mind
The present study used data collected in the past for one purpose and subsequently analysed it for another purpose; this is called a retrospective study. Such studies may cause researchers to inadvertently draw biased conclusions when analysing the data. However, retrospective studies are relatively cheap and simple to implement. They can serve as a starting point in a research process to enable collection of data to explore an idea. Once retrospective data has been analysed, it can be used to develop a funding proposal for a larger prospective study. The implementation of Cabenuva is relatively new and, for now, the study from San Diego should be viewed as a good first step on the path to understanding why some people initiate or do not initiate a regimen of long-acting ART.
In Canada, Cabenuva is subsidized by most provincial formularies.
—Sean R. Hosein
Resources
Summary: HIV antiretroviral medication coverage in Canada – Public Health Agency of Canada
Southern Alberta study assesses who is at risk for HIV viral breakthrough episodes – CATIE News
Long-acting HIV treatment in people with multiple challenges – CATIE News
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- ViiV Healthcare. Cabenuva. Product monograph. 7 December 2022.
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