“On-Demand” Pre-Exposure Prophylaxis (PrEP) for Sexual Intercourse - PrEP 2-1-1 dosing overview

Sep 27, 2026

“On-Demand” Pre-Exposure Prophylaxis (PrEP) using the 2-1-1 dosing strategy is presented as a non-daily option studied in men who have sex with men (MSM). The text explains how it differs from daily FDA-approved PrEP, outlines the timing of taking two pills before sex and one pill at 24 and 48 hours afterward, and notes adjustments when sex occurs within seven days of the last dose. It highlights effectiveness, eligibility limits, testing needs at least every three months, and key trial references such as IPERGAY.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages1

Reading Time3 min

AccessFree to download

What is the Difference Between PrEP and PrEP 2-1-1?

How Does PrEP 2-1-1 Work?

Dosing schedule (2–24 hours before, then 24 and 48 hours after)

Important note for sex within seven days of the last dose

Recommendations, limitations, and clinical trial references

“On-Demand” Pre-Exposure Prophylaxis (PrEP) for Sexual Intercourse | PrEP 2-1-1 or “On-Demand”PrEP is a non-daily PrEP dosing strategy that has been evaluated in men who have sex with men (MSM) and was 86% effective at preventing HIV transmission in a clinical study in Canada and France. The PrEP 2-1-1 protocol shown below is not FDA-approved; however, PrEP 2-1-1 has been endorsed by the International AIDS Society USA. | | --- | | What is the Difference Between PrEP and PrEP 2-1-1? | | Daily PrEP is the FDA-approved use of a daily pill (Truvada® or Descovy®) that combines two drugs to prevent HIV transmission. Many studies have shown that it can reduce the risk of HIV transmission by up to 99% . Studies have been done proving PrEP is effective for men, women, and transgender people, as well as preventing transmission through injection drug use. The United States Prevention Task Force has given PrEP Grade A status.
The PrEP 2-1-1 dosing strategy has not been FDA approved but has been studied with Truvada® and shown to be an effective HIV prevention choice for MSM. PrEP 2-1-1 can prevent HIV transmission during anal sex. PrEP medication absorbs slower into vaginal tissue than anal tissue, so PrEP 2-1-1 is not an effective option for vaginal sex. PrEP 2-1-1 can be an option for people who have less frequent anal sex or for people who are unable or prefer not to take daily PrEP. | | How Does PrEP 2-1-1 Work? | PrEP 2-1-1 starts by taking TWO pills between 2 and 24 hours before sex. Taking the pills closer to 24 hours before sex is better but you can use PrEP 2-1-1 up to 2 hours before sex. After sex, you take ONE pill 24 hours after the first pills, and ONE pill again 24 hours after that. That’s PrEP 2-1-1, get it? |
Take TWO pills 2 – 24 hours before sex. If you know when you’ll have sex, take the pills
closer to 24 hours before sex. | |
Take ONE pill 24 hours after the first dose. | |
Take ONE pill 48 hours after the first dose. | | --- | --- | --- | --- | --- | Important Note: The PrEP 2-1-1 dosing schedule changes if you are going to have sex within seven days of your last PrEP dose. Start by taking just ONE pill between 2 and 24 hours before sex. You still take ONE pill 24 hours after the first pill, and ONE pill again 24 hours after that. Daily PrEP has extensive clinical trial data on safety and efficacy and is the only dosing strategy recommended by the CDC. The State Office of AIDS recommends PrEP and financial assistance may be available through California’s PrEP-Assistance Program (PrEP-AP) for uninsured and insured individuals who meet the eligibility criteria. PrEP 2-1-1 has only been studied in MSM. There is no data and it is not recommended for use in cis-women, cis-men who have sex with women, transgender women and men, people who inject drugs, or people with active hepatitis B coinfection. The PrEP 2-1-1 protocol with Truvada® is the only non-daily strategy with evidence for HIV prevention. PrEP 2-1-1 with Descovy® is not recommended outside of a clinical trial. PrEP 2-1-1 should be prescribed by a healthcare provider and should include HIV and STI testing at least every 3 months. People considering PrEP 2-1-1 should be able to plan or delay their sexual activity so that their first dose is at least 2 hours (and preferably closer to 24 hours) before sex. Select Clinical Trials and References: IPERGAY (Molina et al. NEJM 2015): 400 MSM (France, Canada) randomized toPrEP 2-1-1-vs. placebo. 86% efficacy. Participants took median 15 pills per month. IPERGAY open label extension (Molina et al. Lancet HIV 2017): only one HIV infection detected in 361 MSMover 18 months follow-up. San Francisco Department of Public Health Dear Colleague Letter with recommendations for PrEP 2-1-1: [http://www.gettingtozerosf.org/wp-content/uploads/2018/11/HIVUpdate_02122019_v2.pdf](http://www.gettingtozerosf.org/wp-content/uploads/2018/11/HIVUpdate_02122019_v2.pdf)

FAQs

How does PrEP 2-1-1 differ from daily PrEP?

Daily PrEP is FDA-approved for HIV prevention as a daily pill regimen. PrEP 2-1-1 is non-daily, has been studied in MSM, and is not FDA-approved, though it has endorsements and evidence from clinical studies.

What is the PrEP 2-1-1 dosing schedule for sexual intercourse?

Take two pills between 2 and 24 hours before sex (closer to 24 hours is better). After sex, take one pill 24 hours after the first dose, then one pill again 24 hours later (48 hours after the first dose).

Who should not use PrEP 2-1-1 and what monitoring is recommended?

The text states PrEP 2-1-1 has only been studied in MSM and is not recommended for several groups, including cis-women, cis-men who have sex with women, transgender women and men, people who inject drugs, and those with active hepatitis B coinfection. A healthcare provider should prescribe it with HIV and STI testing at least every three months.

Sep 27, 2026

Uploaded by Blue Pony