An expert authority explains the treatment selection process for a patient, as well as the different ways to administer PrEP.
Frank J. Palella Jr, MD: There are different PrEP options. Until recently, the ones that we talked about were exclusively oral daily pill-taking, either the fixed-dose combination of tenofovir disoproxil fumarate with emtricitabine, the brand name of which is Truvada, or the generic version, the fixed-dose combination of tenofovir alafenamide and emtricitabine, which you are familiar with as Descovy. These require daily pill-taking in order for optimal protection to be provided to patients. More recently, we have the availability of an injectable every 2 months, integrase strand transfer inhibitor, which is long-acting, called cabotegravir, distributed under the commercial name Apretude, which allows for directly observed therapy, in that it is not self-administered by the patient. The medication is distributed by dispensing pharmacies to the clinic, and the injections are undertaken in the clinic every 2 months. We know whether patients have received such therapy. Daily PrEP is the standard of care. If we're talking about pill-taking, other approaches that have been evaluated are what we call on-demand or event-pace-based, meaning that the individual takes PrEP based upon their self-assessment of risk and meaning to say whether they feel they are engaging in usually sexual activity of sufficient risk to warrant taking the medication. In those scenarios, probably for event-based or on-demand PrEP, you are primarily looking at 2 doses of oral PrEP in the 24 hours before the sexual contact—one dose in the 24 hours after and another dose in 24 hours after that. That requires some vigilance on the patient's part regarding attention to such a schedule. It requires foreign knowledge and forethought regarding when they're going to be having sex. As I've mentioned before, that is really the Achilles heel of that approach because data from diverse studies have demonstrated that while that approach can be feasible in certain populations, it's less feasible for many populations, particularly in persons who might have more hectic precarious lives and for whom the ability to anticipate sexual activity is less clear.
In terms of determining what patients should or should not get individual therapies, some types of therapies have not been studied in populations at risk. For example, the populations studied for PrEP were centered primarily on men who have sex with men or transgendered women. Many of the biggest studies like iPrEx, HBTN 083, and others have really centered on those individuals. Hence, we don't have data, for example, for tenofovir alafenamide and FTC, Descovy. It's not FDA approved for vaginal receptive sex, for women who are sexually active. I think we feel less comfortable looking at using that therapy for cisgender women. Conversely, for example, with Apretude, with cabotegravir injectable, every other month, there are robust data from a very new study called HPTN 084, which compared prospectively cisgender women at very high risk. This was an African population, large numbers who received either every-other-month injectable cabotegravir or daily TDFFTC, essentially generic Truvada, and demonstrated a market advantage in terms of preventing new HIV infection for the women receiving the Apretude—a 90% lower likelihood of getting infected with HIV. In that study, we have to consider the fact that those women who received Apretude were getting directly observed therapy, injections every 2 months. The women who were not, we could not attest to their ability to adhere optimally to daily pill-taking. In those types of scenarios, we have to consider whether they had the wherewithal to take the pills in terms of social determinants or other determinants—meaning they would need to disclose that they were trying to protect themselves from HIV and that they were sexually active. This is a diverse set of considerations. We have the luxury now with our current menu of treatment to customize the approach.
This transcript has been edited for clarity.