Pre-Exposure Prophylaxis (PrEP) is a medication regimen used by HIV-negative individuals to prevent HIV infection. It involves taking a combination of two antiretroviral drugs that stop the virus from establishing a permanent infection following exposure. While the most common method requires taking a pill every day, an alternative strategy exists for specific populations called PrEP On Demand (PoD), or event-driven PrEP. This non-daily approach offers flexibility by allowing medication to be taken only around the time of sexual activity.
Understanding the 2-1-1 Dosing Protocol
PrEP On Demand is defined by a specific and rigid schedule often referred to as the “2-1-1” protocol. This sequence describes the number of pills taken across three distinct time points surrounding a planned sexual encounter. The regimen uses the drug combination Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC).
The process begins with a loading dose of two pills taken between two and 24 hours before anticipated sexual activity. This initial double dose rapidly builds protective drug concentrations in the rectal tissue. Following the first dose, the individual takes one pill 24 hours later, and a final single pill 48 hours after the initial two-pill dose.
This structured dosing ensures that protective drug levels are maintained during and immediately after potential exposure. If sexual activity continues for several days, a single pill is taken every 24 hours until two days after the last sexual encounter. Strict adherence to this precise timing is paramount for the regimen to be effective.
Clinical Evidence on Protection Levels
The effectiveness of PrEP On Demand was primarily established by the landmark IPERGAY clinical trial, which studied men who have sex with men (MSM) in France and Canada. The trial demonstrated a significant reduction in HIV acquisition risk for participants who followed the 2-1-1 dosing schedule. The original findings showed an 86% reduction in HIV incidence compared to the placebo group.
This high level of protection is achieved because the two active drugs prevent the HIV virus from replicating if it enters the bloodstream. When the protocol is followed precisely, the drug concentration in the body’s tissues, particularly the rectal mucosa, is sufficient to block the virus. Subsequent analyses suggest that for individuals with perfect adherence, the effectiveness approaches the nearly 99% efficacy seen with daily PrEP.
Who Should Use PrEP On Demand
PrEP On Demand is currently recommended only for a specific subset of the population, primarily cisgender men who have sex with men (MSM). This limitation exists because the clinical trials establishing the 2-1-1 protocol’s efficacy focused on this demographic. PoD is generally only recommended for HIV prevention related to anal sex, as the medication absorbs more slowly into vaginal tissue.
A precondition for using this event-driven method is the ability to reliably predict a sexual encounter at least two hours in advance. Individuals whose sexual activity is highly unpredictable or frequent may find the daily regimen more suitable. PoD is not a recommended or studied option for individuals who engage in receptive vaginal sex, for transgender women on feminizing hormone therapy, or for people whose risk comes from injection drug use.
Choosing Between Daily and On-Demand PrEP
The choice between a daily PrEP regimen and the On-Demand protocol depends on a person’s individual lifestyle, sexual frequency, and type of sexual activity. Daily PrEP, which involves taking one pill every day, offers the broadest and most consistent protection, including for receptive vaginal sex. It is the only option currently recommended for people with unpredictable or frequent sexual activity.
On-Demand PrEP is a viable alternative for individuals who have less frequent sexual encounters and can reliably plan their activity. A benefit of PoD is the reduced overall pill burden, which may be preferable for those who struggle with a daily medication routine.
However, the 2-1-1 schedule requires a higher level of planning and adherence precision around the time of sex. Ultimately, the decision should be made in consultation with a healthcare provider, who can assess the individual’s risk profile and lifestyle factors to determine the most effective strategy.