Post-Exposure Prophylaxis (PEP) is a time-sensitive, short-term medication regimen used to prevent Human Immunodeficiency Virus (HIV) infection after a recent, potential exposure. This treatment is an emergency measure, not a substitute for ongoing prevention methods, and must be initiated as quickly as possible following a risk event. The drugs work by interrupting the initial stages of viral replication, stopping the virus from establishing a permanent infection in the body.
The Standard Treatment Course
The duration of the PEP treatment is a fixed 28-day course of antiretroviral medications. This regimen must be taken every day to maximize the chance of preventing HIV infection. Treatment must start within 72 hours (three days) of the potential exposure, as effectiveness decreases significantly with every passing hour. Starting the medication as soon as possible, ideally within 24 hours, is crucial because the virus begins to replicate rapidly after entering the body.
Taking every dose exactly as prescribed is paramount for maintaining a consistently high therapeutic drug level in the bloodstream. If doses are missed, the concentration of the medication can drop below the level needed to inhibit viral activity. This lapse could allow any replicating virus to multiply unchecked. Completing the full 28 days ensures the drug is present long enough to clear any initial traces of the virus before it can integrate into the body’s cells.
Drug Elimination and Half-Life
The literal answer to “how long does PEP stay in your system” relates to the pharmacological concept of half-life—the time it takes for half of the drug’s concentration to be eliminated from the bloodstream. PEP regimens typically include a combination of drugs, such as Tenofovir/Emtricitabine (TDF/FTC or TAF/FTC) plus a third agent like Dolutegravir or Raltegravir.
Most of these antiviral medications clear relatively quickly from the blood plasma, generally within days, not months. For example, the half-life of Tenofovir in plasma is approximately 17 hours. Dolutegravir also has a long half-life, but the predicted time for it to fall below therapeutic levels after stopping the drug is just a few days. While the drugs themselves are quickly eliminated from the plasma, the active components, such as the metabolite of Tenofovir inside the cells, may persist for several weeks.
The rapid clearance of the primary drug concentration means that the protective effect ceases shortly after the 28-day course is completed. Once the 28 days are finished, the body begins the process of rapid elimination, but medical observation must continue for a longer period.
Monitoring and Follow-Up Testing
Even after the medications have been cleared from the body, a prolonged monitoring period is necessary to confirm that the treatment was successful. This extended observation is required because the powerful antiretroviral drugs used in PEP can temporarily suppress the virus, delaying the body’s immune response. This delay can lengthen the “window period,” which is the time between infection and when a standard HIV test can accurately detect it.
The testing timeline begins with a baseline HIV test taken before starting PEP to ensure you were not already positive. The first critical follow-up test is usually scheduled four to six weeks after the initial exposure. The confirmatory test is typically conducted three months (12 weeks) after the exposure. This 12-week mark is widely regarded as providing a definitive result using modern fourth-generation antigen/antibody tests. Though some older or specific high-risk guidelines may suggest an additional test at six months, a negative result at three months is generally considered conclusive.