PrEP 2-1-1 (sometimes referred to as "on-demand" or "event-driven" PrEP) is a way of taking Truvada to protect against HIV when you need it, instead of every day. Essentially, you take it before and after sex — it is a bit more complicated than that, so please read below under "What is the dosing schedule?". This method is regularly prescribed in some European countries and is fully endorsed by the World Health Organization (WHO), The United States CDC has not officially approved PrEP 2-1-1, but many US healthcare providers are now recommending it. The evidence from research and clinical practice clearly demonstrates that PrEP 2-1-1 is highly effective.

IMPORTANT! PrEP 2-1-1 has been shown to be effective only with Truvada, not with Descovy. There are good reasons to believe that Descovy would also work, but this has not been proven.

Why consider it?

PrEP 2-1-1 can be a good option if sex is less frequent and/or more predictable. Some people want to save money by using fewer pills (if they have sex no more than once or twice a week). The research finds PrEP 2-1-1- is just as effective even if it is used relatively infrequently.

Others want to reduce the potential for side effects. However, some research suggests that intermittent PrEP users may be more likely to experience gastrointestinal and renal (kidney) side effects than daily PrEP users. Still others believe they are more likely to remember to take intermittent PrEP than a daily pill, but there’s some evidence that daily PrEP use results in better average adherence than on-demand use.

The main point, though, is that PrEP 2-1-1 works just as well as daily PrEP, and so people can choose the method that works best for them, subject to the limitation described under "Who can use it?" just below.

Who can use it?

PrEP 2-1-1 has been studied and shown to work in cisgender men who have sex with men. It has not been studied in cisgender women, transgender men or women, or injection drug users. For people who have vaginal/front hole sex, daily PrEP with good adherence (6 to 7 doses a week) is the only regimen that’s been proven to work. The most recent research shows that PrEP 2-1-1 may be significantly less effective in transgender women who take feminizing hormones.

What is the dosing schedule?

On-demand dosing involves the following steps. For a single sexual episode, it requires a total of 4 Truvada pills.

1. Take two pills between 2 and 24 hours before sex (or just one pill if you took your most recent dose within the last 6 days).
2. Take a single pill 24 hours after the first dose.
3. Take another single pill 24 hours after the second dose.
4. If additional sex events take place before the above regimen is completed, continue one pill daily until 48 hours after the last sex event.

What lab tests are recommended?

Certain lab tests are recommended before you start to use on-demand PrEP – just as for daily PrEP. If you order your Truvada or generic equivalent online, you may be able to obtain the necessary testing through a local healthcare provider or sexual health center.

Is there good evidence that this works?

PrEP 2-1-1 has been tested and proven highly effective in a trial called IPERGAY conducted in 2012-14, which enrolled 400 HIV-negative, cisgender men who have sex with men. Among the subjects given Truvada (including those who did not always take it), HIV infections were reduced by 86% compared to those given a placebo. No one who took the pills as directed acquired HIV. Even users who had relatively infrequent sex were protected, according to an analysis released in 2017. A follow-up “open-label” study (everyone was given the real medication), with 361 participants, showed a 97 percent reduction in HIV diagnoses, including those who did not take the medication.

Based on this strong research evidence, PrEP 2-1-1 has been fully endorsed by the World Health Organization (WHO).

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