HIV PrEP has the potential to revolutionize HIV prevention in the U.S. and worldwide. For many, the daily pill can offer up to 99% protection from acquiring HIV. So why are so few people taking it? The Centers for Disease Control and Prevention (CDC) estimates that 1.2 million would benefit from PrEP in the US, but as of 2016 only 77,000 reported PrEP use. As an HIV prevention specialist, I’ve heard from many patients who think daily PrEP is not right for them. The reasons vary, but a core issue is the lack of choices when it comes to how someone takes PrEP. A common refrain I hear is that “I don’t have sex that often, so do I really need to take a daily pill? That just seems like a waste!” So, is PrEP worth it if you’re having sex less than once weekly? Ever heard of “on-demand” PrEP? Because it may be the solution you’ve been waiting for.
Since 2015 the option of on-demand PrEP has been rising as an alternative for HIV Prevention. The concept first came about after the landmark study called IPERGAY. In that study, a routine called “2-1-1” dosing was tried for PrEP among cisgender gay men. It went like this: take 2 pills 2-24 hrs before sex, 1 pill 24 hrs later, and 1 pill 24 hrs after the prior dose. For people who didn’t have at least 2 “sex free days” following the initial double dose, they continued taking a daily tablet until no further sexual activity had occurred.
2-1-1 PrEP, How Effective Is It?
The original IPERGAY trial showed that 2-1-1 PrEP reduced the risk of HIV acquisition by 86% compared to the placebo group. The level of protection was so great that the researchers were compelled to end the placebo group early because to continue withholding 2-1-1 PrEP from that group would be unethical. 2 people acquired HIV who were in the study compared to 16 in the placebo group and there is some controversy as to whether these two patients were taking PrEP correctly or may have already been exposed to HIV prior to starting 2-1-1 PrEP. An extension of IPERGAY following cisgender gay men over more time showed HIV risk reduction closer to 97%.
Why Is the Science So Confusing?
If the 2-1-1 procedure was the same for both studies, why the different estimates of HIV protection? Well, the next phase in the study no longer had a placebo group and in a sense it’s like comparing apples and oranges. A placebo-controlled trial is done when it’s not certain whether a certain medication will work or not. Once it’s known to work very well, that’s when placebo groups go away. When that happens, how the statistics are done will change. This happens in research all the time. You try researching the same medication in the same way but there’s always something different that you cannot control.
More 2-1-1 PrEP studies were done to see if these high levels of protection would be seen in more real-world settings where 2-1-1 PrEP was part of routine medical visits and not part of structured research. That brings us to the Prevenir Study in 2018 out of Paris, France. By this time, the European AIDS Clinical Society had already approved 2-1-1 PrEP for use among cisgender gay men. This study followed 1,435 cisgender men at high risk for acquiring HIV with about half doing daily PrEP and the other 2-1-1 PrEP. After a full year of follow up, there were zero HIV infections in both groups. Again, supporting the conclusion that 2-1-1 PrEP is an excellent alternative to daily dosing.
Who Should Use 2-1-1 PrEP?
People who have less frequent sex (less than weekly) and who can wait 2-24 hrs before having sex would be good candidates. They have to withhold sex long enough for the first dose to take effect. If sex tends to be very spontaneous to the point that the PrEP pills are nowhere to be found when needed, daily PrEP is probably the better choice. Taking fewer pills can also mean lowering the chances of experiencing bone or kidney side effects which can occur in a small group of people taking Truvada long term for PrEP. However, 2-1-1 would not be a good way to avoid “startup” side effects such as nausea, headache, or disrupted sleep. These uncommon side effects tend to go away with regular use of Truvada and come back anytime the medicine is stopped and then restarted.
2-1-1 for Transgender Patients?
Although not recommended yet, hopefully it will be soon. Remember, these HIV protection estimates came from studies that limited the focus to cisgender gay men where rectal exposure was the main risk of HIV exposure. This means that for transgender men and women (and even heterosexual men, women, and people who inject drugs) 2-1-1 has not been evaluated enough to know whether it could work just as well for other routes of HIV exposure.
Who Endorses 2-1-1 PrEP in the US?
Although the CDC has not yet endorsed 2-1-1 PrEP, many think they will do so soon because many other leading organizations in HIV prevention and public health have already endorsed it. The list of major endorsements includes the International Antiviral Society – USA Division, the Departments of Public Health for New York City and San Francisco, and the list continues to grow.
Ask Your PrEP Provider
It’s possible if your PrEP provider is less experienced in providing HIV prevention services, they may not know about 2-1-1 PrEP. In the internet era, physicians have gotten used to getting articles from savvy patients. Bring the NYC Public Health article on 2-1-1 PrEP for doctors to your visit and advocate for the services you need.
Don’t have a HIV PrEP provider? Visit Ochsner.org/PrEP. Rapid PrEP starts are available with Dr. Garnett Friday afternoons at the Tchoupitoulas Health Center. You can also visit our site or call our PrEP Hotline for an appointment 855-241-9347. I welcome questions, feedback, and requests for future topics at DrG.HIVWarrior@gmail.com.