Long-acting injectables represent a transformative advancement in HIV prevention. However, for that transformation to be realized, we must first address emerging and longstanding barriers to HIV prevention that limit access to these new modalities. POSITIVELY AWARE convened three national experts—Rupa R. Patel, Kirk Grisham and June Gipson—with varied expertise and experience to explore the importance of long-acting injectable cabotegravir for PrEP, the policies needed to increase access, lessons learned from oral PrEP programs and other critical considerations for scale-up. Patel has over 15 years’ experience in clinical medicine, research and public health program development in HIV prevention and is affiliated with Washington University in St. Louis. Grisham is a social science researcher and policy analyst with over 10 years’ experience in academic- and community-based public health settings. Gipson is the president and CEO of My Brother’s Keeper, Inc. and has worked in public health for over 20 years, guiding the establishment of Mississippi’s first LGBTQ+ primary healthcare clinic.
What is important about long-acting injectable cabotegravir PrEP?
Kirk Grisham: What strikes me as important about long-acting PrEP is that this new modality offers users a real choice, between daily pill taking and an injection every couple of months. For some, such as those who find adherence to ongoing pill taking challenging and folks who are unstably housed, this is a PrEP option that may be especially helpful.
June Gipson: As Kirk mentioned, the primary game-changing attribute of these injectables is their extended dosing intervals. Patients no longer need to remember a daily pill, significantly reducing pill burden. This not only enhances convenience but can also improve adherence, making it a pivotal development in the ongoing effort to prevent HIV. Just as the evolution of HIV treatment to a single pill and the introduction of PrEP in 2012 revolutionized access and utilization, long-acting injectables further elevate this progress, aligning with the fast-paced and technologically advanced world we inhabit.
Rupa Patel: Long-acting injectable PrEP represents a shift in how we, as a healthcare ecosystem, can better support retention and adherence by engaging in directly observed therapy (DOT). It holds promise for those who face pill stigma or forget their pills. When a PrEP client reports they desire taking a pill every day but cannot, this may help. Cabotegravir (name brand Apretude) is highly efficacious, has minimal side effects, is taken every two months and may evolve into an even better product. For instance, at some point we may be able to inject fewer doses over a year, we could evolve to smaller dose volumes and we may be able to administer the injections in multiple sites on the body so it can be given by partners or oneself.
Describe the current barriers to implementing long-acting cabotegravir for PrEP.
Gipson: There are multiple challenges despite its promising potential. First and foremost, the cost is a significant hurdle. Cabotegravir is prohibitively expensive. If insurance companies don’t provide coverage or only offer limited coverage, many people may find it unaffordable. Furthermore, the healthcare landscape in the South and other areas of the U.S., with vast rural areas, poses another challenge. Due to a shortage of primary care providers in numerous regions, many people already grapple with accessing basic healthcare, let alone injectable PrEP.
Patel: For this product to have so many advantages, national rollout has been rather slow. This is due to several intersecting things, including complex workflows related to insurance-related coverage and paperwork, insurance reimbursement, organizational financial risk for medication purchases, logistics related to medication shipment and documentation and appointment scheduling. The need for a properly trained workforce to deliver the injections, overall staff shortages and prescriber awareness and comfort also come into play. Community awareness and comfort with the intervention remain challenging.
Grisham: As June and Rupa mention, one of the biggest barriers to implementation, and future long-acting PrEP, is capacity. Administering this is a heavy lift. For many sites already doing this work, there is a single “champion” making sure all moving parts are working to ensure people get their shots. What happens if this single champion leaves? It’s not sustainable. We really need to develop policy solutions that reduce provider burden, among other things!
From left: June Gipson, PhD, is the CEO of My Brother’s Keeper, Inc. Kirk Grisham, MPH, is an associate with the O’Neill Institute for National and Global Health Law, Georgetown University Law Center. Rupa R. Patel, MD, MPH, is a research associate professor of medicine (Voluntary), Division of Infectious Diseases, at Washington University in St. Louis.
What policies are needed to accelerate implementation of cabotegravir and future long-acting options for PrEP?
Patel: We need to empower trained professionals to deliver it in locations outside of traditional clinic settings. Policies need to focus on task shifting so an array of professionals who are not doctors or nurses can perform intramuscular injections. We need to be able to deliver this product, nationally, as a billable service in community settings, mobile vans, pharmacies and street locations by trained peers to reach those who are largely left out of PrEP services. Insurance and other kinds of coverage must include laboratory tests and staff time as well as the medication.
Grisham: Rupa is spot on. Long-acting injectable PrEP should be a billable service in a variety of settings. A lot of us are talking about the de-medicalization of PrEP, which is critical, but we also need to talk about de-stigmatization and undoing the siloing of HIV-related services. In terms of policy, we need the PrEP shot to be as accessible as a flu or COVID shot. I live in Washington D.C. and when I wanted my flu shot and my COVID booster, I was able to walk 10 minutes down the street and get both without delay. Granted, cabotegravir cannot be as easily administered as these vaccines, but people are working on adapting its administration, and we could soon have a long-acting injectable version of PrEP that will be administered subcutaneously (lenacapavir). The communities most impacted by COVID are often also impacted by HIV. It makes sense to integrate these services.
Gipson: To effectively reduce barriers across the U.S., several policy interventions are imperative. Firstly, a key concern is limited healthcare access in many states. Addressing this requires the expansion of Medicaid. Without Medicaid expansion, a significant portion of a state’s population has no healthcare coverage, leading to reduced access to essential services, including HIV prevention and care. However, even if Medicaid were to be expanded, many folks face a dearth of healthcare professionals, particularly those specialized in HIV. As a remedy, more policies should be crafted to incentivize healthcare professionals to provide HIV services in underserved regions. Such incentives might include loan forgiveness programs, tax breaks or competitive compensation packages.
Equally vital is the need to bolster public awareness about HIV. Comprehensive campaigns that educate residents about HIV prevention, testing and treatment options, including injectable PrEP, should be launched. Collaborating with community leaders, religious figures and influential personalities in the state can help in shaping public opinion and reducing HIV stigma.
‘We must offer choices at each visit. People may want to switch between oral, injectable and other future options. We must build PrEP services around the ability to offer PrEP choices.’
What do we need to consider from the PrEP user perspective?
Gipson: From the user’s perspective, several factors play a pivotal role in the acceptance and sustained use of injectable PrEP. Foremost is accessibility. If the medication is marketed as a breakthrough but remains out of reach, due to insurance constraints or a provider shortage, it can breed distrust. This can dampen enthusiasm, hindering the adoption of this new intervention. Equally significant is the method of administration: injections. It’s crucial to gauge the community’s comfort level with receiving regular injections. While the idea of forgoing a daily pill may seem appealing to some, it introduces a different kind of inconvenience. Users would need to make regular visits to a clinic for their injections. In states like Mississippi, where transportation can be a significant challenge, this could be a deterrent and especially burdensome in rural areas, where clinics may be few and far between. The logistical challenges of frequent clinic visits need to be weighed against the benefits. Taking these considerations into account helps ensure injectable PrEP programming resonates with users’ needs and concerns.
Patel: PrEP users also have different needs and desires over time. We must offer choices at each visit. People may want to switch between oral, injectable and other future options. We must build PrEP services around the ability to offer PrEP choices.
Grisham: Exactly! Similarly, not everyone is going to want to receive PrEP in a de-medicalized context. For some, traditional forms of engagement with a doctor in a clinic is preferred. For others, there may be more interest in hybrid models, perhaps doing a telehealth visit and then receiving their injection in a secondary space by a traditional provider. What is most important is that we increase user agency and autonomy so there is choice when it comes to engaging their provider on how their PrEP is administered. We want to provide multiple points of entry for the diversity of prevention users.
How to apply the lessons learned from current oral PrEP programs to long-acting options?
Grisham: Some of the most promising oral PrEP programs involve telehealth and/or pharmacies to deliver PrEP. Telehealth has a role in the rollout of injectable PrEP, but there is still the matter of administering the injection. One of telehealth’s greatest strengths is the ability to engage with PrEP users who may not have access to a brick-and-mortar provider. There is a critical need to build up networks of sites connected to telehealth that can administer injectable PrEP, including pharmacies.
Patel: We must build PrEP injection programs inspired by the community-facing oral PrEP programs that encompass one-stop, same-day, hybrid/telehealth, self-collection lab kits, delivery in diverse settings (e.g., homes, vans, pharmacies or other community locations) and provision by a varied workforce (e.g., pharmacists, medical assistants, trained peer workers and nurses). We must develop user-focused programs that combat stigma, medical mistrust, discomfort, cultural insensitivity and product misinformation. Today, we still have some provider discomfort with oral PrEP and we need to continue to address this barrier and incorporate injectable PrEP in skills-based education for providers. PrEP has been an important gateway to care and other services that foster overall well-being. Therefore, all types of PrEP provision must be developed in tandem with provision or referrals to an array of services including mental health, substance use, food and housing, employment, insurance, legal, vaccination and primary care.
Gipson: Successfully including injectable PrEP into PrEP programming involves not only logistical changes but a deep understanding of the needs and concerns of healthcare providers and clients. Healthcare providers need thorough training regarding injectable administration, its distinct advantages, potential side effects and monitoring protocols.
On the client front, clear communication about the distinctions between the kinds of PrEP are crucial. This includes discussing the convenience of fewer doses with injectable PrEP against the commitment to periodic injections, which can be a decisive factor. Healthcare providers should have a system in place that not only monitors the well-being of patients on injectable PrEP, but also collects their feedback. This allows for real-time adjustments based on client experiences. The role of case management is central. Case managers can assist with adherence to injection visits by tracking clients’ injection schedules, offering reminders and addressing concerns. Lastly, while injectable PrEP is an innovative addition to HIV prevention services, and it might be a game-changer for many, it’s not a one-size-fits-all solution. Some might find oral PrEP more suitable or may prefer it in certain life stages or circumstances. Recognizing and respecting client choice must remain at the heart of successful and sustained prevention strategies.
Are we re-medicalizing PrEP by incorporating an injection? How do we de-medicalize prevention?
Grisham: I think this is an important question. PrEP advocates have been making great strides to decrease barriers and increase access to HIV prevention for oral PrEP. Provider administered prevention, on the other hand, relies heavily on medical systems. Yet if we see de-medicalization as a continuum, we can push for models in and outside of the clinic that decrease barriers and de-medicalize injectables. These may be hybrid models where telehealth is used to prescribe and a brick-and-mortar location is used for administration, or even at-home delivery/administration. Pop-up testing and vaccination as well as mobile clinics were crucial to the COVID response and will be critical to de-medicalized models for injectable prevention.
Patel: Introducing injections, and other future forms of injections and implants, have the potential to “medicalize” PrEP. We need to be hyperaware of building programs that involve peer community staff, safe spaces and welcoming environments. We also must move injection delivery out of the conventional clinic setting and closer to where PrEP users are—e.g., homes, shelters, bars, meet-up venues, stores, HIV/STD testing locations and other community areas. We can learn a lot from global medicine programs in Africa and South Asia, and look at family planning injections, voluntary male medical circumcision and various maternal and child health programming which have successfully de-medicalized complex care to better serve communities.
Gipson: De-medicalizing access to injectable PrEP, while a promising approach in certain contexts, faces significant obstacles across the U.S., particularly in southern states. Primarily, the challenges lie not just in the administration of the medication but in the broader healthcare infrastructure. Many states grapple with pervasive insurance issues; many residents lack adequate coverage, and even if access to injectable PrEP were simplified, the cost barrier remains insurmountable for many. Moreover, the shortage of physicians, particularly those specialized in HIV, exacerbates this challenge. Simplifying who can administer the injection, while logical, doesn’t address the root problem. If patients can’t afford the treatment or don’t have easy access to healthcare due to various constraints, the change in administration doesn’t fundamentally shift the accessibility paradigm. Without addressing the core issues of insurance coverage and the lack of healthcare providers, the move to de-medicalize PrEP administration in Mississippi might be akin to putting a band-aid on a deeper wound.