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Future of PrEP
The Future of PrEP: Shifting from a Therapeutic to a Preventive Paradigm

Released: November 28, 2023

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Key Takeaways
  • PrEP empowers individuals by providing them with a discreet, user-controlled HIV prevention method.
  • Barriers to PrEP include the requirement for adherence to a daily pill, difficulty accessing healthcare facilities that provide PrEP, and healthcare professional prejudice against prescribing PrEP.

We have had an amazing 40 years of research and discovery in HIV. A landmark for all of this has been the development of antiretroviral agents—first to treat HIV and now as pre-exposure prophylaxis (PrEP).

PrEP is a Revolutionary Tool for HIV Prevention
Initially, our options for prevention were quite limited. We called them the ABCs: Abstain from sex, be faithful to a single partner whose status is known, or use condoms. This messaging excluded a large proportion of the population at risk of HIV acquisition because it is not always possible, for young women for example, to request that a male condom be used to ensure safer sex. 

The wonderful thing about PrEP is how it puts prevention in the hands of the individual. Unlike suppressing viral load with antiretroviral therapy in people living with HIV, which is an indirect way of preventing HIV, PrEP provides a discreet, user-controlled prevention method. I have heard people describe PrEP as taking back their own sexual destiny. For many, PrEP has allowed them to reclaim the pleasure of their sexual lives by taking away the risk and fear of HIV acquisition. By taking a pill a day, anyone can prevent HIV for themself. It is powerful, and it is empowering.

Barriers to Realizing the Full Potential of PrEP 
So why is PrEP adoption still so limited? I find that one of the biggest barriers to oral PrEP is the notion of a daily pill. For a portion of the population, taking a pill every day is challenging if they are not regularly at risk of HIV exposure. From their perspective, they do not want to be taking a pill if they are not having sex. They may find it difficult to remember to take medication when there is not an immediate need. For others, pill aversion can be a barrier.

Other barriers I see are more systemic. For example, where we prescribe PrEP can be a barrier because our delivery models often are not suited to healthy individuals with busy schedules. Having to show up at a health facility may deter people from obtaining PrEP because of potential exposure to illnesses and the time commitment it takes to go through that system.

Furthermore, there has not been great awareness that these PrEP interventions are available. Demand has not been as good as it should be. I think part of the reason is that, as healthcare professionals, we have not always embraced the concept of PrEP because of negative associations with using an antibiotic or an antiviral to prevent disease. These misconceptions can limit our opportunities to educate and offer PrEP to individuals. We must overcome prejudice in this regard and recognize that these are antiretrovirals, but they are being used for prevention. I think it is profoundly important for us to shift from a therapeutic paradigm to a preventive paradigm.

The field is working to reduce these barriers as much as possible, with simplification, demedicalization, and improving service delivery. I think the next revolution in PrEP will be the widespread adoption of different delivery methods and long-acting (LA) PrEP. 

Beyond the Paradigm of Daily Oral PrEP
I think of the next generation of PrEP modalities as superheroines in that they move us beyond the paradigm of daily pills. The first variation to that model is the 2:1:1 regimen, also known as event-driven PrEP, coitally dependent PrEP, or on-demand PrEP. This regimen enables people to take pills only around the time they are sexually exposed. The 2:1:1 regimen entails 2 tablets 2-24 hours before sex, 1 tablet 24 hours later, and another tablet 48 hours after the first dose.

If people are having sex infrequently and are certain of the times they will be engaging in sex, this regimen can greatly reduce the number of pills they need to take. However, the 2:1:1 regimen is currently recommended only for men because of a lack of clinical evidence in women.

Next on the horizon are LA modalities. One example is the dapivirine vaginal ring, a nonnucleoside reverse-transcriptase inhibitor‒infused vaginal ring that lasts for 28 days. A terrific thing about the dapivirine ring is that there is no lasting activity after removal, resulting in less risk of resistance mutations arising if an individual were exposed to HIV soon after stopping PrEP. There is also very little systemic absorption when using the ring, resulting in low risk of systemic adverse events. It is available in some low- and middle-income countries but has not been approved by the FDA or made available in the United States.

Another example is the exciting notion of LA injectables, such as LA cabotegravir (CAB). LA CAB is an integrase inhibitor that has to be dosed only once every 8 weeks. It is a large-volume injection administered into the muscles of the buttock, which unfortunately can be quite painful. However, for many, the benefits of 2 months of protection outweigh the pain.

Even longer‒acting injectable PrEP also is being investigated, such as LA lenacapavir, a capsid inhibitor being studied as twice-yearly PrEP in the phase III trials PURPOSE-1 and PURPOSE-2.

Service Delivery
Another element of next-generation PrEP is innovation in service delivery. For example, at my clinic, we now offer both oral PrEP and the vaginal rings as couriered PrEP. This means that after people initiate PrEP, they can get maintenance PrEP via a postal order or delivery service.

Unfortunately, couriered PrEP is not feasible with LA CAB PrEP because we need a trained individual to administer the injection. However, I think there are ways we can make implementation of LA CAB more scalable by having clinics whose sole purpose is to provide maintenance injectable doses. 

In all, I think it is an exciting time for HIV prevention. Similar to how LA reversible contraception changed the face of reproductive choice for women globally, these options for HIV prevention empower people to choose a modality that suits their individual preferences and needs for their personal life stage. I believe working toward more widespread PrEP implementation will further reduce new infections and bring us closer to epidemic control. 

The Path Forward
Of course, prevention can work only if it is used, and it can be used only if it is available. We must do our utmost to ensure that prevention is available and affordable to all. This is where I think the most work needs to be done in the near future to ensure that new PrEP modalities are globally and equitably available for all.

Your Thoughts?
What barriers have you encountered in your practice with implementing LA PrEP, and what are you most looking forward to in the future with PrEP? Leave a comment to join the discussion.