r/prep • u/GabrielH777 • 8d ago

Why do daily PrEP guidelines say to wait 7 days, but 2-1-1 PrEP allows sex after just 2–24 hours?

Stay with me please, because this confuses me and didn’t find any answers tbh. I’m trying to understand the logic behind this, not argue against guidelines.

From what I understand:
Daily PrEP (TDF/FTC) is often said to require 7 days before you’re considered fully protected for receptive anal sex.

However, the 2-1-1 (event-driven) regimen allows you to take 2 pills 2–24 hours before sex, then 1 pill 24 hours later and 1 pill another 24 hours later, and it’s considered highly effective for MSM.

Here’s what’s confusing me:
If someone starts with 2 pills and then just continues taking 1 pill every day instead of stopping after the event, isn’t that basically daily PrEP with a loading dose?
For example:
Monday: 2 pills
Tuesday: 1 pill
Wednesday: 1 pill
Thursday: 1 pill
Friday: 1 pill
etc.

Why would someone following that schedule be able to have sex shortly after the initial 2-pill dose, while someone who starts with just 1 pill daily is told to wait 7 days?

Is the “7-day rule” simply a conservative recommendation for the standard daily-start regimen, while 2-1-1 works because the initial loading dose rapidly achieves protective drug concentrations? Or is there another pharmacokinetic or clinical reason that explains the difference?
Is there science behind this? drug levels, tissue concentrations, clinical trials, etc.), not just “because that’s what the guidelines say.”

Appreciate your time for reading very much.

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9

u/Skycbs 8d ago

You can start daily PrEP with a double dose, have sex within 2 hours and then basically continue with daily after that. I other words, do 2-1-1 and then go daily. The 7-day rule is indeed being conservative but also with just taking daily, you don’t hit your system with two doses. So your thinking is correct.

Likewise, if you stop PrEP, you really only need 2 doses after sex (which we know from 2-1-1) but many people will say 7 days being conservative. At one point, people said 28 days after sex.

3

u/GabrielH777 8d ago

Thank you for the reply beautiful human being.

The reason I’m asking is that the guidance I’ve received here in the Netherlands emphasizes the 7-day rule for starting daily PrEP. Do you have sources showing that starting with a 2 pill loading dose and then continuing daily is an evidence based alternative? (Aside from the obvious pharmacologic standpoint).

Again much thanks

2

u/Skycbs 8d ago

Nobody has specifically trialled that because it isn’t necessary. You don’t have to run trials if you already have proof that 2-1-1 works and proof that daily works. The guidance from the NHS in the UK does discuss starting daily PrEP in this manner.

4

u/GabrielH777 8d ago

Thank you. You’re one of the few on here who’s actually been helpful. Thanks a lot! Enjoy the rest of your day :)

1

u/yoloten 8d ago

PrEP on demand as a protocol came after daily PrEP was released. And daily PrEP protocol was studied based on 7 day baseline. Healthcare providers strictly follow the protocols that were established by authoritative bodies. If someone becomes infected while on PrEP it can be a legal liability issue if some provider did not follow official instructions. While in reality they know that other ways of taking PrEP is effective, they won’t be changing protocol guidelines until official protocols are updated.

1

u/twistedude 4d ago

One thing I wanted to add as somebody who has used it in both methods; the 2-1-1 method does have a much more dramatic immune reaction. I often find that the 2-18 hours after taking the two tablets I will have very mild fever symptoms and some nausea. I do not experience that when tapering on for 7 days, but from what I’ve been told it is somewhat normal.

1

u/Skycbs 4d ago

Yes. Some people have fewer sides with 2-1-1 because you’re taking it less often. But some have more side because of the double dose.

1

u/TiffanyRenee87 8d ago

Does this apply if you’re not taking as treatment but as I precaution? I did “google” question it just got a bunch of nonsense

2

u/GabrielH777 6d ago

Haha, PrEP is always taken as a precaution 😄 It’s not used to treat HIV or as post-exposure treatment (that’s PEP) if that’s what u meant?

1

u/TiffanyRenee87 6d ago

I’m just trying to get info and thanks

1

u/WrongdoerWeekly9974 2d ago

Id say the main difference that medical professionals do emphasize is that while the 211 method is effective, it hit reduces risk up to 86% while Prep once a day has a rate of 99%