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Q&A: PrEP 2-1-1 for anal sex

By Chris Hall, MD, Pierre-Cedric Crouch, PhD, ANP-BC, ACRN and Janessa Broussard, NP

In the U.S., PrEP is prescribed as a medication (Truvada) taken once per day (“daily PrEP”) for HIV prevention. Some European countries, Canada and Australia have endorsed another dosing option for people using Truvada PrEP called “PrEP 2-1-1,” “PrEP on-demand,” “event-based dosing,” in addition to other names. This strategy involves taking Truvada for PrEP around times of sex instead of once every day, and research has shown that this way of taking PrEP is effective in preventing HIV infection. 

Currently, some health organizations are recommending PrEP 2-1-1 to clients. If you’re curious about how PrEP 2-1-1 might work in your own life, here are answers to frequently-asked questions we get about PrEP 2-1-1.  

How do you take PrEP 2-1-1? 

PrEP 2-1-1 involves taking two Truvada tablets 2-24 hours before sex, one tablet 24 after the first dose and one final tablet 24 hours after the second dose. If you have sex more than 24 hours after taking your first dose, or over multiple days, you will need to continue taking one tablet every day until you have taken two doses, 24 hours apart, following the last time you have anal sex. Read the specifics about how to take PrEP 2-1-1 here (look at the section titled “On Demand PrEP or Event Based Dosing”).

PrEP 211 dosing

Is PrEP 2-1-1 right for me? 

PrEP 2-1-1 is effective for anal sex and may be a good option for people who have less frequent anal sex. Maybe you have sex a few times a month, and don’t want to worry about having to take a pill every single day. You may find that PrEP 2-1-1 is a good option that fits with your lifestyle and how often you have sex. 

Although PrEP 2-1-1 is effective for anal sex, it is not effective for vaginal or front hole sex. Truvada does not concentrate easily in vaginal tissue and needs a daily dose to be most effective. Taking PrEP daily works very well to prevent HIV during vaginal or front hole sex. 

PrEP 2-1-1 may also not work as well for people taking estradiol or testosterone. If you are taking estradiol or testosterone, we recommend that you take daily PrEP. PrEP 2-1-1 will be effective for trans and non-binary people not taking hormones if they have anal sex only. 

How do hormones affect PrEP 2-1-1? 

Testosterone and estradiol may affect the levels of PrEP in the body. We recommend that people taking estradiol or testosterone take daily PrEP instead of PrEP 2-1-1. 

Truvada does not affect how well hormones work, so you can take daily Truvada for PrEP at the same time as hormones including testosterone and estradiol.   

How old do I have to be to access PrEP 2-1-1? 

Truvada is approved for adolescents who weigh over 35 kg (77 lbs). Talk to your health care provider if you have questions about using daily PrEP or PrEP 2-1-1 and you are under age 18.   

Does PrEP 2-1-1 work for tops? 

Yes. PrEP 2-1-1 was studied in people who had insertive anal sex (who were the “top”). PrEP 2-1-1 is as effective for tops as it is for bottoms when having anal sex. 

What happens if I miss a dose? 

With PrEP 2-1-1, it is very important to not miss doses. Daily PrEP is more “forgiving” of missed doses than PrEP 2-1-1 because over time you build up levels of medication in your body by dosing every day. With PrEP 2-1-1 you do not have this “build up” of medication in your body so you need to take all of the doses for it to work well to prevent HIV. 

If you miss a dose, immediately take two of your Truvada pills and contact the clinic or medical provider where you get medical care or PrEP services. You may need to immediately begin post-exposure prophylaxis if there is a chance you were exposed to HIV. 

Can I switch between daily PrEP and PrEP 2-1-1?

You can switch between daily PrEP and PrEP 2-1-1. You may begin using PrEP 2-1-1 dosing and then start having sex more frequently. In that situation, you could simply continue taking one pill every day as long as your sexual activity continues or as long as you feel comfortable taking one pill daily.

If you are taking daily PrEP you may decide to begin taking PrEP 2-1-1 if you go through a period where you are having sex less often. In this case, you would stop taking a pill every day seven days after you have last had sex. When you start having sex, you would need to take the first dose of two Truvada tablets 2-24 hours before you have sex, and then continue with the 2-1-1 dosing strategy described above.

Thing to keep in mind:

  •   Start PrEP 2-1-1 by taking 2 pills 2-24 hours before your first sexual encounter
  •   Stop PrEP 2-1-1 by taking 2 final doses (24 hours apart) after you last have sex

Is there less risk of side effects with PrEP 2-1-1 compared to daily PrEP?

Generally, the side effects of daily Truvada for PrEP are mild and resolve after a few months of taking the medication. A small percentage of people experience gastrointestinal side effects. Small declines in kidney function also occur in some people. Bone mineral density has also been found to decline slightly in some people, although the effects seem to reverse once PrEP is stopped. 

The potential side effects of PrEP 2-1-1 are the same as those for daily PrEP based on data from a 2-1-1 study where people were taking an average of four pills per week. If you’re using PrEP 2-1-1 and you’re taking less than four pills per week, it’s possible that these side effects may be even less likely to happen.   

Is PrEP 2-1-1 a good way to conserve Truvada pills? 

PrEP 2-1-1 is not a good option for people who are running out of Truvada with daily PrEP or otherwise want to conserve their medication. If you’re worried about access to medications or not having enough pills, a better option might be for you to look for ways to increase your access. Many people buy generic PrEP. Check out iwantprepnow.co.uk for more information about buying generic PrEP online.

Is there risk of drug resistance with PrEP 2-1-1?

Drug resistance is only a concern in the context of HIV infection. If you stay HIV-negative, you will not develop drug resistance. To stay HIV-negative while you take PrEP 2-1-1, make sure you take all of the correct doses and use PrEP 2-1-1 every time you have sex. It is important that you NOT pick and choose the sexual encounters when you use PrEP 2-1-1. 

Use PrEP 2-1-1 every time you have sex to achieve the desired results! 

Do I still need to get labs and HIV and STI testing done every three months with PrEP 2-1-1? 

We recommend that you still get HIV testing, STI testing and labs done every three months while you are taking PrEP 2-1-1 (or as frequently as your healthcare provider recommends). 

Will I have problems with my insurance using PrEP 2-1-1? 

While you take PrEP 2-1-1, your health care provider will continue to prescribe Truvada PrEP to you with instructions for daily use. They will need to do this in order for the medication to be covered by patient assistance programs and other insurance. Fill your prescription as usual–every month–when you are taking PrEP 2-1-1.   

What follow-up appointments do I need if I take PrEP 2-1-1? 

It’s recommended that people using PrEP 2-1-1 go to all of the same clinic appointments as people taking daily PrEP. The follow-up for people taking daily PrEP and PrEP 2-1-1 is the same.

Is there risk of seroconverting with PrEP 2-1-1?

There has been news coverage of a person who seroconverted (became infected with HIV) while using PrEP 2-1-1. Although we don’t know the details of the case, we remain confident in the research supporting PrEP 2-1-1 as a highly effective way to prevent HIV infection for people having anal sex, when it is used as directed by a trained medical provider.

In the largest research study of PrEP 2-1-1, there have been zero “breakthrough” HIV infections among people using PrEP 2-1-1 dosing. Although there may be some people who seroconvert while taking PrEP 2-1-1, we are confident that this will be rare. It’s a challenge not to overreact to the cases as we encounter them. Keep in mind that they do not measurably change the overwhelming efficacy of PrEP 2-1-1 or daily PrEP. 


If you have questions about PrEP, email prep@sfaf.org.

San Francisco AIDS Foundation offers both daily PrEP and PrEP 2-1-1 dosing options. Find out more and schedule an appointment. 

Chris Hall, MD, MS, AAHIVS is the vice president of medical affairs at San Francisco AIDS Foundation and has more than 30 years of experience in the HIV moment as a leader, clinical provider, researcher and policy advocate.

Pierre-Cédric Crouch, PhD, ANP-BC is a PrEP provider and nursing director at Magnet for San Francisco AIDS Foundation.

Janessa Broussard, RN, MSN, AGNP-C, is a nurse practitioner and nurse manager at San Francisco AIDS Foundation.