Antiretroviral therapy not only helps people living with HIV maintain their health, it also can prevent acquisition of the virus.

Post-exposure prophylaxis (PEP) involves taking a short course of antiretroviral medications, usually for a month, after a high-risk exposure. To be most effective, PEP should be started as soon as possible. It must be started within 72 hours after exposure, but within 24 hours is best.

While pre-exposure prophylaxis (PrEP), which is taken in advance of potential exposure, requires just one or two drugs to prevent HIV from taking hold in the body, PEP—which is essentially very early treatment—requires a full three-drug regimen.

The latest guidelines from the Centers for Disease Control and Prevention, updated in May 2025, recommend two once-daily regimens taken for 28 days:

  • Biktarvy (bictegravir/tenofovir alafenamide/emtricitabine), a complete all-in-one regimen.
  • Dolutegravir plus either tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) plus either emtricitabine (FTC) or lamivudine (3TC). This is usually taken as Tivicay plus TDF/FTC (Truvada or generic equivalents) or Tivicay plus TAF/FTC (Descovy). 

Both regimens are generally safe and well tolerated. TDF can cause impaired kidney function and minor bone loss in susceptible people. TAF, a newer version of tenofovir that is easier on the kidneys and bones, is preferred for people with pre-existing kidney disease or poor kidney function. (Click here to learn more about the differences between TDF and TAF.)

The same two PEP options are recommended for adults, adolescents, pregnant women and children ages 2 to 12 years. The previous recommended regimen, raltegravir (Isentress) plus TDF/FTC, is still an acceptable option, but it has a higher pill burden. Alternative regimens may be considered in special situations.

PEP is recommended after a nonoccupational exposure that “presents a substantial risk for HIV transmission,” for example, condomless anal or vaginal sex or sharing needles with an HIV-positive person who does not have sustained viral suppression or whose status is unknown. If you suspect a high-risk exposure to HIV, contact your health care provider or local hospital emergency room as soon as possible.

Starting PEP within 72 hours can sometimes be difficult, as potential exposures may occur when it’s not easy to access the medications, such as over a weekend or while traveling. PEP is typically provided on an emergency basis after the fact, but giving people pills to keep on hand in case of accidental exposure—an approach know as PEP-in-pocket—can be a good option for some people.

Click here for the POZ HIV Prevention Drug Chart for info on the available options for PEP.

Last Reviewed: July 7, 2025