Pre-exposure prophylaxis (PrEP) is a biomedical HIV prevention approach that significantly reduces the likelihood of HIV acquisition. Currently, PrEP is approved in oral pill form (Truvada, emtricitabine/tenofovir disoproxil fumarate), which is designed to be taken daily to prevent HIV acquisition with optimal adherence. Gay, bisexual, and other men who have sex with men (MSM) are disproportionately impacted by HIV, and PrEP has the potential to significantly reduce the number of new HIV cases among this group as well as other highly impacted groups, including transgender women, injection drug users, serodiscordant couples, and individuals experiencing intimate partner violence.

The Centers for Disease Control and Prevention (CDC) has estimated that about 1.2 million people in the United States are at high risk for HIV infection and would greatly benefit from PrEP. However, only between 130,000 and 135,000 people in the U.S. are currently on PrEP, with barriers to PrEP uptake ranging from high cost to psychosocial issues, lack of knowledge, health care provider discrimination, and housing instability, among others.

But some things are changing that may make less than daily use of PrEP a real option for gay and bisexual men who do not or cannot take PrEP daily. In late July, the World Health Organization (WHO) updated its recommendation to include event-driven PrEP (ED-PrEP) as a PrEP usage modality for men who have sex with men (ED-PrEP is also called 2+1+1, intermittent PrEP, or PrEP on demand). ED-PrEP for gay, bisexual, and other MSM is defined as taking a double dose (two pills) of Truvada two to 24 hours before a sexual encounter, followed by another pill 24 hours after the double dose and another pill two days after the double dose.

The new WHO ED-PrEP guidelines state that event-driven dosing might be appropriate for those MSM who: 1) engage in infrequent sex (defined as less than two times a week on average), 2) are able to plan for sexual encounters two hours or more prior or can delay sex for that time period, and 3) express ED-PrEP to be convenient and effective for them. Currently, the WHO does not believe ED-PrEP is appropriate for cisgender or transgender women, transgender men engaging in vaginal sex, cisgender men engaging in vaginal or anal sex with women, or any individuals with chronic hepatitis B. As it does for daily oral PrEP users, the WHO recommends routine HIV and sexually transmitted infection testing for those on ED-PrEP.

While the event-driven nature of ED-PrEP may drive an increase of PrEP uptake among gay, bisexual, and other MSM, due to cost savings from fewer prescription refills and lower pill burden, there are several considerations to be made about the practicality of its use, especially related to anticipated sex events, which may not mirror real-life circumstances under which sex occurs.

"Event-driven PrEP is ideal for MSM who believe that they can anticipate when sexual risk will occur, and it should be included, along with daily PrEP, as another viable option in PrEP provision among MSM at high risk of HIV acquisition," said Matthew Mimiaga, Sc.D., M.P.H., a professor of behavioral and social sciences and epidemiology at the Brown University School of Public Health. "I think that most MSM will prefer daily PrEP over event-driven PrEP, because they may not always know when they will engage in sexual risk."

However, he offers words of caution: "Event-driven PrEP requires MSM to be more mindful and may limit 'sexual spontaneity,' which may be less appealing to some. If someone is taking very few doses each month, coupled with the short amount of time before sexual behavior, it is plausible that drug concentrations may not be at the level of full protection in rectal tissues, as it would be with taking daily PrEP."

The Research That Led to Event-Driven PrEP

Initially, the official recommendation from CDC and WHO for PrEP was daily oral use to ensure optimal protection from HIV. This addition to the WHO PrEP guidelines is informed by findings from the IPERGAY study, which found that using PrEP in the ED-PrEP modality reduced risk for HIV infection by 86% among gay, bisexual, and other MSM at high risk for HIV. In 2017, results from an extension of the IPERGAY study were released, and ED-PrEP was demonstrated to be highly effective in reducing HIV incidence (new cases of HIV) by 97%. Most recently, at the International AIDS Society Conference on HIV Science held in Mexico City in July, a study of 3,057 participants taking either daily PrEP or ED-PrEP found only two people in the study contracted HIV, providing further evidence of the effectiveness of ED-PrEP. The culmination of scientific evidence of the effectiveness of ED-PrEP resulted in this recommendation addition specifically for gay, bisexual, and other MSM, a group that accounted for two out of every three new cases of HIV in the United States in 2016.

Some jurisdictions in the U.S. are beginning to implement event-driven PrEP. In June 2019, New York City's Department of Health and Mental Hygiene announced a move in this direction. As more public health programs try to figure out how to implement ED-PrEP, it is important to consider how ED-PrEP may affect current daily PrEP users as well as individuals who are currently not on PrEP but considering it.

Will Event-Driven PrEP Increase Uptake Among Black Gay and Bisexual Men?

"This recommendation will not change how I take PrEP. There isn't enough data for me to fully believe its efficacy. I will stick to my one pill a day method," said Courtney Johnson, a black gay man who currently lives in New York City and uses PrEP daily.

Furthermore, Johnson provides insight about the feasibility of predicting a sexual encounter, the ultimate cornerstone of ED-PrEP: "This recommendation is sort of an invitation for people to push the limits of using PrEP. It opens the door for people to intentionally miss doses of PrEP, which then increases the risk of seroconversion. Asking people to predict when they are going to have sex in certain instances is not realistic."

For gay and bisexual men who are currently not on PrEP, there is a decision to be made about which PrEP modality will work best: ED-PrEP or daily PrEP.

"There is still a lot for me to consider, but I do like the availability this allows in the case I do decide to get on PrEP," said Ryan Breckenridge, a 26-year-old filmmaker based in Atlanta. "I recognize the benefits of being on PrEP; however, my main determining factor is whether it's truly beneficial for me, especially since I'm not currently sexually active, and my sole sexual partner is in another state and on PrEP himself."

It is important that health care providers who see gay and bisexual men engage in nuanced and honest conversation about their HIV prevention arsenal and how PrEP may fit into the equation.

"It will be interesting to see how much interest is generated by this new recommendation," said Raphael J. Landovitz, M.D., M.Sc., infectious disease physician and co-director of the UCLA Center for HIV Identification, Prevention, and Treatment Services. "I think more options for dosing increase the breadth of acceptability, but I don't think this will dramatically increase uptake -- that is, I don't think this is a game changer. For that, I think we'll need long-acting or extended-release type preparations."

More importantly, it is imperative that pharmaceutical companies ensure affordability and access to their medications, specifically in communities that stand to benefit the most from their products.