Pre-Exposure Prophylaxis (PrEP) is a medication taken by individuals who are HIV-negative to prevent acquiring the human immunodeficiency virus (HIV). PrEP combines tenofovir and emtricitabine, which work by blocking the virus from replicating. Understanding how long PrEP “lasts” involves two distinct phases: the time needed for the drug to build up to protective concentrations and the time it takes for the drug to clear the body after the medication is stopped. The duration of effectiveness depends on achieving and maintaining sufficient drug levels in the tissues where the virus might enter the body.
Achieving and Maintaining Protective Drug Levels
For PrEP to be fully protective, the medication must reach a concentration known as “steady state” within the target tissues. Steady state is the point where the amount of drug entering the body from a daily dose equals the amount naturally eliminated by the body. This buildup phase is necessary because the drug components must be converted into their active forms inside the cells of the immune system.
The time it takes to reach protective levels varies depending on the specific tissue. For receptive anal sex, the drug concentration in the rectal tissue reaches a high, protective level after approximately seven days of consistent daily dosing. Achieving maximum protective concentrations in cervicovaginal tissue, relevant for receptive vaginal sex, takes longer, requiring about 20 to 21 days of daily dosing. This difference in tissue saturation highlights why medical guidance on PrEP initiation can differ based on the specific type of exposure risk.
The Half-Life and Washout Period: How Long PrEP Remains Detectable
The duration PrEP lasts after the last dose is explained by the pharmacological half-life of its components. The half-life is the time it takes for the concentration of a drug in the bloodstream to be reduced by half. The half-life of the active drug forms inside the immune cells is much longer than in the bloodstream.
The prolonged presence of the active drug within the cells provides a buffer of protection, but it also dictates the “washout period.” The washout period refers to the time required for the drug to be completely cleared from the system. The half-life of the active tenofovir component inside peripheral blood mononuclear cells, a type of immune cell, can be around 6.25 days. It generally takes about 5.5 half-lives for a drug to be almost entirely eliminated from the body.
For most people, the washout period is approximately 28 days after the last potential HIV exposure. This extended timeframe ensures that all traces of the drug are gone from the body’s tissues. A complete washout is necessary because if a person acquired HIV while stopping PrEP, the remaining low drug levels could promote the development of drug-resistant HIV strains. Therefore, the 28-day period is often recommended before comprehensive HIV tests, such as resistance testing, can be performed accurately.
Individual Factors Influencing PrEP Clearance
The rate at which PrEP clears the body can vary between individuals due to several biological and behavioral factors.
The most immediate influence is adherence, as missed doses prevent the drug from maintaining the necessary steady-state concentrations in the tissues. Even a lapse in consistent dosing can dramatically lower the drug’s protective efficacy, particularly in tissues that require higher concentrations for protection.
Individual metabolism also plays a role in how the body processes and eliminates the medication. Both tenofovir and emtricitabine are primarily cleared through the kidneys, meaning a person’s kidney function directly affects the drug’s clearance rate. Individuals with declines in estimated glomerular filtration rate (eGFR), a measure of kidney function, typically clear the drug more slowly. This slower clearance can prolong the time the drug remains in the system.
Additionally, the specific drug formulation can influence clearance rates. The two common oral PrEP options contain either tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF), both combined with emtricitabine. TAF requires a lower dose because it is metabolized more efficiently into the active form within the cells. This difference can lead to varying clearance dynamics and potentially less impact on kidney function for some users.