What 2-1-1 PrEP is
Daily PrEP keeps a steady level of medicine in your body all the time. On-demand PrEP, also called event-driven, intermittent or 2-1-1 PrEP, builds protection right before sex and keeps it up for two days afterward. The name describes the pill count: 2 pills before, then 1, then 1.
The schedule comes from the French IPERGAY trial, published in the New England Journal of Medicine in 2015. In that trial, men who have sex with men who used F/TDF around sex had an 86% lower rate of new HIV infections than men taking a placebo. That result is why several international guidelines now include event-driven dosing as an option.
In the United States, the FDA-approved schedule for Truvada is still one pill every day. 2-1-1 is an off-label use. CDC's clinical guidance says it isn't a CDC-recommended regimen, but clinicians may prescribe it to people who fit specific criteria (below).
How to dose 2-1-1, step by step
Every dose is one standard tablet of emtricitabine/tenofovir disoproxil fumarate (F/TDF), the drug in Truvada and its generics.
- Before sex: take 2 pills together, 2 to 24 hours before sex. Closer to 24 hours gives you more margin. Taking them less than 2 hours before doesn't give the drug enough time.
- 24 hours after the double dose: take 1 pill.
- 48 hours after the double dose: take 1 pill.
- If you keep having sex on the following days: keep taking 1 pill every 24 hours. Stop once you've taken two daily pills after the last time you had sex.
| Example | When you take pills |
|---|---|
| Sex Saturday at 10 p.m. | 2 pills Saturday at noon · 1 pill Sunday at noon · 1 pill Monday at noon |
| Sex Friday and Saturday nights | 2 pills Friday at noon · 1 pill Saturday at noon · 1 pill Sunday at noon · 1 pill Monday at noon |
Keep the timing tight. Set alarms for the follow-up doses at the moment you take the double dose. The doses after sex aren't optional. They're part of what makes the schedule protective.
Starting again later: if it has been a while since your last dose, start over with the two-pill dose before sex. Restart rules after a recent dose vary between guidelines, so ask your prescriber which rule they use and write it down. That way you're not guessing in the moment.
Who 2-1-1 is for
Guidance differs a little depending on who wrote it.
CDC (United States)
CDC's clinical guidance says event-driven F/TDF may be prescribed to adult gay and bisexual men who:
- ask for non-daily dosing,
- have sex infrequently, meaning less than about once a week, and
- can reliably take the first dose at least 2 hours before sex.
World Health Organization
WHO's 2022 implementation guidance says event-driven oral PrEP is appropriate for preventing sexual HIV acquisition among all cisgender men and trans and gender-diverse people assigned male at birth who are not taking estradiol-based hormones. Several other professional bodies, including European and British HIV groups and IAS-USA, also support event-driven PrEP for gay and bisexual men.
Who it tends to suit in practice
- People whose sex is occasional and can be planned a few hours ahead, like a weekend away or a planned date.
- People who'd rather not take a pill every day when they aren't having sex for weeks at a time.
Who should not use 2-1-1
2-1-1 is not the right choice if any of these apply to you:
- Receptive vaginal or front-hole sex. F/TDF takes longer to build up in vaginal and cervical tissue than in rectal tissue, and event-driven dosing hasn't been shown to protect against vaginal exposure. Use daily oral PrEP or an injectable instead.
- HIV risk from injecting drugs. Event-driven dosing was studied for sex, not injection exposure.
- Active hepatitis B. Tenofovir and emtricitabine also suppress hepatitis B. Starting and stopping them over and over can trigger hepatitis B flares, which can damage the liver. CDC says event-driven PrEP isn't appropriate for people with active hepatitis B.
- Taking estradiol-based gender-affirming hormones. WHO's event-driven guidance excludes people on estradiol. Daily PrEP works with hormone therapy.
- Adolescents, or anyone who may struggle with a complex schedule. CDC lists these, including people with active substance use disorder, as poor fits for event-driven dosing.
- Using Descovy. Descovy (F/TAF) hasn't been studied on a 2-1-1 schedule. Only F/TDF can be used this way.
If you're not sure whether you have hepatitis B, you'll find out before you start, because hepatitis B testing is part of the standard PrEP workup. Our PrEP for women guide and PrEP for transgender women guide cover the options that fit those situations.
2-1-1 vs daily PrEP vs injections
| On-demand (2-1-1) | Daily oral | Injectable | |
|---|---|---|---|
| Drug | F/TDF only | F/TDF or F/TAF (Descovy) | Apretude (every 2 months) or Yeztugo (every 6 months) |
| FDA-approved schedule? | No (off-label) | Yes | Yes |
| Vaginal / front-hole exposure | Not recommended | F/TDF yes; Descovy not indicated | Yes |
| Planning needed | At least 2 hours before every time | None once protection is built | Keep injection appointments |
| Hepatitis B | Not appropriate with active HBV | Needs monitoring; don't stop without a plan | Doesn't treat HBV; screening still matters |
For a fuller side-by-side, see oral vs injectable PrEP and our Descovy vs. Truvada page.
Testing and follow-up are the same as daily PrEP
Using fewer pills doesn't mean less follow-up. Truvada's prescribing information says PrEP should only go to people confirmed HIV-negative right before starting and at least every 3 months during use. That's because taking a two-drug regimen with undiagnosed HIV can lead to drug resistance. Expect:
- An HIV test before your first dose, then about every 3 months.
- Hepatitis B testing at the start, and vaccination if you're not immune.
- Kidney function checks, because the drug is tenofovir disoproxil fumarate.
- STI testing, since PrEP doesn't prevent syphilis, gonorrhea or chlamydia. Our sister site explains why PrEP visits include STI testing.
Many people switch between daily and on-demand dosing as their lives change, for example daily during a busy summer and 2-1-1 during quieter months. If you want to do that, set up the plan with your prescriber ahead of time. Our first-month guide covers what starting PrEP feels like.
If something goes wrong
If you had sex without the two-pill dose beforehand, or you missed the follow-up doses and aren't sure you were protected, don't wait. If the exposure was within the last 72 hours, PEP (post-exposure prophylaxis) may still prevent HIV. See how to get PEP fast. If you're on daily pills instead, the first-month guide explains what to do after a missed dose.
Frequently Asked Questions
Can I use Descovy for 2-1-1 dosing?
Is 2-1-1 PrEP FDA-approved?
Can women use on-demand PrEP?
What if I have sex several days in a row?
What if I forgot the doses before sex?
Do I still need regular HIV tests on 2-1-1?
Sources
- CDC HIV Nexus: Clinical Guidance for PrEP (event-driven F/TDF dosing section)
- World Health Organization: implementation guidance for simplified and differentiated PrEP delivery (July 2022)
- Molina et al. On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection (IPERGAY). N Engl J Med, 2015
- aidsmap: Should event-driven PrEP be an option for women? (March 2024)
- Truvada U.S. prescribing information (Gilead Sciences)
This guide is general health information, not medical advice, and it doesn't replace a conversation with a clinician who knows your history. Guidance and program rules change; we last reviewed this page on October 12, 2026. Spot something out of date? Tell us.