- Long-acting injectable PrEP will hopefully be approved in the spring of 2024 in Canada
- Long-acting PrEP has been approved in the U.S. – learning from their experience may be useful
- Researchers in Philadelphia studied barriers to long-acting PrEP and ways to overcome them
Regulatory authorities in Canada are reviewing a dossier on long-acting (LA) injectable PrEP to prevent HIV. The dossier contains information on the drug cabotegravir, which has already been approved in Canada and the United States for injectable HIV treatment (Cabenuva) and oral HIV treatment (Vocabria). Cabotegravir for HIV treatment and for PrEP are both manufactured by ViiV Healthcare. Cabotegravir for PrEP is sold under the brand name “Apretude” in the U.S. and other countries.
Apretude has now been tested in clinical trials of several thousand people. In those trials, it was found to be highly effective and statistically superior to a daily pill containing tenofovir DF + FTC (this pill is sold as Truvada and is available in generic formulations). Ultimately, Apretude is given once every two months. This can make taking the medication much less burdensome. Hopefully it will be approved for use in Canada in late spring 2024.
Apretude has previously been approved in the United States. It will be instructive to learn from the rollout of injectable PrEP in that country so that Canadian clinics, doctors, nurses and pharmacists can prepare for the launch of the drug in this country.
A team of researchers in Philadelphia interviewed key stakeholders who were at a large clinic. These were doctors, nurses, pharmacists and other clinic staff, as well as patients who used oral and long-acting injectable PrEP. The interviews were designed to elicit information about how injectable PrEP was implemented and to understand issues that affected its deployment. Researchers interviewed 12 clinic staff and 13 patients (seven who used oral PrEP and six who used injectable PrEP).
On average, staff had worked in the clinic for slightly more than three years and most patients were cisgender men. There was one cisgender woman and two transgender men.
Barriers in the clinic
Clinic staff identified the following barriers to the deployment of injectable PrEP:
- lack of education and promotion about the drug
- lack of provider awareness of the drug
- discomfort among providers about the use of PrEP (because they lacked knowledge about using the injectable version)
- limited staff capacity to manage, track and perform outreach to eligible patients
The researchers stated that “providers that did not share similar social and gender identities as their patients who were more likely to request or need PrEP” were "probably less likely to consider PrEP as an option for their patients.”
They also stated that participants were frustrated by “provider bias that tended to target specific populations for their PrEP prescribing, such as [...] cisgender and White gay men, instead of offering and promoting the medicine without gender identity or sexual orientation bias.”
Barriers among patients
Stigma and the cost of injectable PrEP were major barriers identified by patients. For instance, the researchers stated that some patients “did not feel comfortable picking up the medication at the pharmacy as other people might overhear that they were picking up an HIV-related medication.”
The researchers found that some patients did not wish to be perceived at high risk for getting HIV. The patients who complained about this felt that such a label alienated straight-identified men who might find injectable PrEP useful. Patients also felt that being labelled “high risk” further stigmatized LGBTQ+ people.
Insurance issues
Unlike many other high-income countries, the U.S. does not have universal health care. Instead, access to medicines and services is provided through a complex system that is often costly. The researchers stated that injectable PrEP “was associated with burdensome insurance workarounds to ensure that the medication was covered.” What’s more, they stated that “insurance coverage for [Apretude] was generally unreliable, subject to change, caused delays in receipt of the medication, and was perceived by patients to be a barrier to getting [the drug].”
Help
The support of pharmacists and other clinic staff was essential in helping patients access the drug. According to the researchers, “pharmacists acted as the interface between the patient, providers, and clinic by sending reminders for [lab tests], letting patients and providers know when medication is ready, and reminding patients when they are due for injections.” The pharmacy team also provided support to patients by helping them find and overcome hurdles with insurance coverage. In addition, the researchers found that having a PrEP navigator at the clinic was a useful resource for patients.
Issues with Apretude
Note that Apretude is injected deep into the buttocks every two months. These injections are done by a healthcare provider. Some patients complained about injection site reactions—pain and swelling. In clinical trials, injection site reactions did occur and were generally mild-to-moderate and temporary. Over time, in clinical trials such reactions occurred less frequently.
Some patients have gluteal implants or a body mass index (BMI) greater than 30 kg/m2. The latter population requires longer needles to ensure that the drug is injected into muscle. People with gluteal implants must discuss this with their physician. The physician can examine them and determine where in the buttocks the injections can occur so that the drug is injected into muscle rather than the implant.
Some patients felt that pills were more trustworthy than a drug which needs to be injected. Other patients expressed fear of needles and therefore preferred an oral pill for HIV prevention.
As injectable PrEP represents a new technology for HIV prevention, some patients felt concern and apprehension about its efficacy and safety. The researchers stated that other patients perceived it as “more serious” because it was injectable instead of pills. This seriousness was a concern because the drug is injected and slowly released, and some patients worried that side effects could not be easily resolved.
The researchers stated that patients who were not cisgender men “often mentioned not knowing if they could take injectable PrEP, as they felt it was not advertised to them in media, by their providers, or within their communities.”
Attractiveness of injectable PrEP
Patients found injectable PrEP a compelling option for HIV prevention because there was no need for taking pills over the long term. The lack of a pill bottle that they would need to keep at home gave them relief from stigma. The researchers stated that “patients described feeling peace of mind and not having to remember [to take] a daily pill made them feel better protected.” What’s more, the researchers also stated that “patients who were already taking other oral medications appreciated not having to take more pills.”
Both patients and providers felt that shared decision-making concerning the use of injectable PrEP was a factor that they found attractive. The researchers stated that “patients often learned about [injectable PrEP] from social media and their social networks.”
Rolling out injectable PrEP
There were some issues with deploying Apretude at the clinic after it was approved. Most of these seemed to be issues around workflow and having laboratory tests done prior to injecting the drug.
Bear in mind
Although there are initially bound to be challenges with the rollout of injectable PrEP at clinics in Canada, these can be minimized with prior planning and discussion. Not all of the issues experienced in the Philadelphia study will apply to Canada, but many issues will.
The researchers called for programs to “train and inform providers about all PrEP modalities to increase comfort among providers and to normalize patient-provider discussion about PrEP and HIV risk. PrEP navigators, an important system-wide resource in this setting, were instrumental in supporting PrEP prescribing. PrEP navigators can bridge the communication gap between patients and providers and address issues of trust, especially among marginalized groups of patients.”
The researchers also found that pharmacists were one of the “critical facilitators” to the rollout and implementation of long-acting PrEP.
Apretude ultimately needs to be injected every two months and patients will need lab tests prior to injections and be prepared to visit clinics every two months. The researchers warned that some of these barriers “may be insurmountable for marginalized populations vulnerable to HIV.”
Finally, the researchers stated that “both patients and providers described a patient-centred approach to HIV prevention. Such an approach emphasizes the autonomy of the patient in an environment that fosters mutual trust and respect that centres around patients meeting their HIV prevention needs and social goals.” The researchers added that “all PrEP options should be presented to patients and discussed in the context of their own preferences”, which will “foster trust with patients and empower them to engage in PrEP care.”
—Sean R. Hosein
Resources
HIV pre-exposure prophylaxis (PrEP) resources – CATIE
HIV post-exposure prophylaxis (PEP) resources – CATIE
REFERENCE:
Keddem S, Thatipelli S, Caceres O, et al. Barriers and facilitators to long-acting injectable HIV PrEP implementation in primary care since its approval in the United States. JAIDS. 2024; in press.