On-Demand PrEP (2-1-1): How to Take It, Who It Suits, Who Should Not

Many people tell me, "I want to be protected against HIV, but I don't have sex often enough to take a pill every day." For them, on-demand PrEP, known as PrEP 2-1-1, may be the answer. You take it only around the times you are at risk, you use less medicine, and research shows it works extremely well when the timing is right. But this schedule has clear conditions about who can use it and who should not.

What is PrEP 2-1-1?

It means taking PrEP containing tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) or lamivudine (TDF/3TC) around specific events (event-driven PrEP) instead of every day. The World Health Organization endorsed this schedule in 2019, and Thailand's PrEP guidelines include it as an option. The IPERGAY study, published in the New England Journal of Medicine in 2015, found it reduced HIV infection by 86% compared with placebo, and in the open-label phase where everyone received the real medicine, as well as in the Prévenir study in France, almost no infections occurred in people who took it correctly.

How to take it

1. 2 tablets together 2–24 hours before sex. The closer to 24 hours, the more confident you can be, but never less than 2 hours.
2. 1 tablet 24 hours after the first two.
3. 1 tablet 48 hours after the first two.

That is 4 tablets in total for a single event. You can take them with or without food. You only have about 2 hours' leeway on timing, so set alarms.

If you have sex over several days in a row

Keep taking 1 tablet every 24 hours for as long as you are having sex, then take 2 more after the last time (one a day for 2 days).

If you stopped less than 7 days ago

If your last tablet from the previous round was taken within the past 7 days, the new round can start with 1 tablet instead of 2. If it has been more than 7 days, start with 2 tablets as usual. If you are unsure, starting with 2 tablets is the safer choice.

1. 2–24 h before
   2 pills together

   Before sex; never less than 2 hours ahead

2. +24 h
   1 pill

   Counted from when you took the first 2 pills

3. +48 h
   1 pill

   4 pills in total for a single event

4. Several days in a row
   1 pill every 24 h

   While you keep having sex, then 2 more days after the last time

Timing can be off by about 2 hours. Set an alarm. If you miss a dose and had a risk, contact a doctor within 72 h.

Who is it for?

• Men who have sex with men (MSM), including people assigned male at birth who are not taking estrogen
• People who have sex infrequently, for example fewer than 2 times a week, and usually know at least 2 hours in advance
• People who can take tablets accurately on time
• People who want to use less medicine or reduce costs

If you have sex often or unpredictably, daily PrEP is usually easier and less likely to go wrong. See the details in PrEP: HIV prevention before exposure.

Who should not use 2-1-1

• Anyone having vaginal or frontal sex, both women and men with female partners, because the medicine builds up more slowly in vaginal tissue. Daily PrEP is needed.
• Transgender women or anyone taking estrogen. There is not yet enough data for on-demand dosing, so daily PrEP is recommended. See also Feminizing hormone therapy.
• People with chronic hepatitis B. Starting and stopping repeatedly can cause hepatitis flares.
• People using F/TAF. There is no evidence yet to support 2-1-1 dosing with it.
• People who use drugs during sex to the point where they cannot keep track of dose times may be better suited to daily PrEP. Read Chemsex.

Suits 2-1-1

• MSM and people assigned male at birth not on estrogen
• Infrequent sex, known at least 2 h ahead
• Can time pills accurately

Take daily instead

• Vaginal sex
• Transgender women, or anyone on estrogen
• Chronic hepatitis B
• On F/TAF, or substance use makes timing unreliable

vs

Confirmed by IPERGAY (NEJM 2015) and endorsed by WHO since 2019.

Before starting and while using it

The same as daily PrEP: you need a negative HIV test before starting, tests for hepatitis B, kidney function and STIs, and follow-up every 3 months. If you had a risk within the 72 hours before starting PrEP, you need to be assessed for PEP first.

Common mistakes I see

• Taking the first 2 tablets but forgetting the 24-hour and 48-hour doses, so the protection is incomplete
• Taking only 1 tablet before sex instead of 2
• Taking it only after sex, which is not PrEP and does not protect as well as PEP
• Using this schedule for vaginal sex

Switching between 2-1-1 and daily PrEP

You can switch according to what is happening in your life. For example, during a holiday, with a new partner, or at times when you have sex more often, you might switch to daily PrEP, then go back to 2-1-1 when things settle down. When men who have sex with men stop daily PrEP, they should keep taking it for 2 days after the last risk. Compare all the options in PrEP vs PEP.

No form of PrEP protects against other sexually transmitted infections. Condoms, regular STI tests and, for some people, Doxy-PEP help fill that gap.

How the clinic can help

At Dr. Kris Clinic, I help you assess whether 2-1-1 suits your lifestyle, do blood tests before you start, explain how to take it with a reminder schedule, and follow you up every 3 months, both at the clinic and online anywhere in Thailand. English-speaking consultations are available.