HIV PrEP medication as in the blue pill
PrEP On-demand is one of the method of taking HIV PrEP (Pre-Exposure Prophylaxis) for HIV Prevention. The efficacy of On-demand PrEP is 86% or more in terms of protection. This method only works in certain individuals according to the research. Find out more about PrEP On-Demand 2-1-1 (Event-driven PrEP) in this article.
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PrEP On-Demand, also known as Event-driven PrEP or On-demand 2-1-1, is a flexible HIV prevention method for individuals who do not require daily medication. Unlike traditional PrEP daily, this PrEP method is taken before and after potential exposure to HIV, such as during sexual activities. This method is especially useful for those who have less frequent exposure to HIV risk factors.
On-demand PrEP (2-1-1) is implemented using TRUVADA, which is a combination of Tenofovir Disoproxil Fumarate (TDF; 300 mg) and Emtricitabine (FTC; 200 mg) in a single tablet, or any other generic of TRUVADA such as TENO-EM, TENOF-EM, RICOVIR-EM. It was shown to be highly effective for gay and bisexual men in the French IPERGAY study. 
However, a newer PrEP formula DESCOVY, which is a combination of tenofovir alafenamide (TAF; 25 mg) and emtricitabine (FTC; 200 mg) in a single tablet, is approved as daily PrEP in USA but it has not yet been evaluated for the Event driven PrEP.
This method works by providing a high concentration of the medication in the bloodstream during periods of potential HIV exposure. Clinical studies have shown that PrEP On-Demand can be highly effective when taken correctly.
how to take on demand PrEP 2-1-1
Ref: https://www.nyc.gov/assets/doh/downloads/pdf/ah/prep-on-demand-dosing-guidance.pdf
  • Initial Dose: Taking two pills 2-24 hours before potential HIV exposure.
  • Follow-Up Doses: Taking one pill 24 hours after the initial dose, and another pill 48 hours after the initial dose.
  • If you have sex again before the end of this 48-hour period, you should continue to take PrEP once every 24 hours until 48 hours after their last sexual episode
  • If you have sex after the last pill but within 7 days, loading with one tablet then continue 1 tablet once every 24 hours until 48 hours after their last sexual episode
  • Loading with 2 tablets if you are going to anticipate new sexual activity if your last dose was over 7 days. Continue taking PrEP once every 24 hours until 48 hours after their last sexual episode
  • If you haven’t taken PrEP at least 2 hours before the sexual risk activity and/or the PrEP hasn’t been continued for 2 another 2 days. What you need is HIV PEP (Post-Exposure prophylaxis for HIV).
PrEP on demand
PrEP On-Demand is suitable for individuals at intermittent risk of HIV exposure. This includes those who engage in occasional unprotected sex, have partners with unknown HIV status, or participate in sexual activities where condom use is inconsistent. It is essential to consult with a healthcare provider to determine if PrEP On-Demand is the right choice based on individual risk factors and lifestyle.
  • Individuals Not Frequently Sexually Active: Those who have infrequent sexual activity but want protection during those times.
  • People at Risk or with Impaired Kidney Function: Those who need an HIV prevention method without daily medication due to kidney health concerns.
  • Non-Commitment to Daily PrEP: Individuals who struggle with the commitment required for daily PrEP.
  • Inconsistent Condom Users: Individuals who do not always use condoms and need an additional layer of protection.
  • Cost Concerns: Those who find daily PrEP cost-prohibitive and prefer a more economical solution.
  • Heterosexual Cisgender Women and Men: This group has not been extensively studied for PrEP On-Demand, and other methods are recommended.
  • Transgender Individuals on Hormone Therapy: Hormone interactions need more research, making daily PrEP a safer option.
  • Individuals with Hepatitis B: Those who are hepatitis B carriers or have chronic hepatitis B infection should avoid PrEP On-Demand due to potential health complications and instead consider other HIV prevention strategies.
PrEP 2-1-1, or “On-Demand” PrEP, is a non-daily dosing strategy that has been evaluated in men who have sex with men (MSM) and was found to be 86% effective at preventing HIV transmission in clinical studies conducted in Canada and France. Although not FDA-approved, on-demand PrEP has been endorsed by the International AIDS Society USA.
  • IPERGAY Study: Published in the New England Journal of Medicine, the IPERGAY study was a randomized, placebo-controlled trial that began in February 2012. It was stopped in October 2014 due to high efficacy, enrolling 400 participants. The study evaluated a 2-1-1 regimen of tenofovir plus emtricitabine (Truvada) taken before and after sex. The regimen reduced HIV risk by an average of 86% among MSM.1 However, researchers caution that this regimen’s efficacy among MSM with less frequent sex or other high-risk populations remains uncertain.
  • Prevenir Study: Published in The Lancet, the “Prevenir” study aims to enroll 3,000 people in the Paris metropolitan region. Interim results from 1,600 participants over a three-year observational period (May 2017-May 2020) showed no new HIV infections in either arm of the trial. Specifically, there were zero HIV infections over 361 person-years of follow-up in the on-demand group.2
Pharmacological studies have shown that individuals achieve target levels of PrEP medications in colorectal tissue 98% of the time 24 hours after an initial two-pill dose, and 81% of the time two hours after taking a two-pill dose. The IPERGAY study demonstrated that intermittent dosing effectively protects against HIV during both receptive and insertive anal sex, suggesting robust protection with on-demand dosing schedules.
On-demand PrEP, using Truvada®, requires planning and timely dosing before sex, unlike daily PrEP recommended by the CDC. It needs a healthcare provider’s prescription and offers high but not 100% protection.
  • Anticipate Sexual Activity: On-demand PrEP works best when you can plan or delay sexual activity. The first dose should be taken at least 2 hours before sex, with a preference closer to 24 hours.
  • Dosage with Truvada®: The on-demand PrEP protocol with Truvada® is the only non-daily strategy with proven efficacy for HIV prevention. On-demand PrEP with Descovy® is not recommended outside of clinical trials.
  • Regular Testing: On-demand PrEP should be prescribed by a healthcare provider. The HIV Testing & STD Testing every 3 months are required at least every 3 months.
  • Additional Protection: While PrEP is highly effective, it is not 100% foolproof. Condoms provide additional protection against HIV and other STDs. Post-exposure prophylaxis is recommended if you forget to take PrEP as directed.
PrEP on demand
  1. On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection <https://www.nejm.org/doi/full/10.1056/NEJMoa1506273> ↩︎
  2. Daily and on-demand HIV pre-exposure prophylaxis with emtricitabine and tenofovir disoproxil (ANRS PREVENIR): a prospective observational cohort study <https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(22)00133-3/abstract> ↩︎