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HIV post-exposure prophylaxis (PEP)

Summary

Post-exposure prophylaxis, or PEP, is a way to help prevent the transmission of HIV in an HIV-negative person who may have been recently exposed to the virus. It involves taking HIV medications as soon as possible after a potential exposure to HIV. Anyone who thinks they may have been exposed to HIV should contact their healthcare provider, a hospital emergency room or sexual health clinic immediately to ask about PEP. 

PEP is very effective but will not prevent 100% of HIV transmissions from occurring. It must be started within 72 hours of exposure to HIV. For PEP to be effective, a person must have high adherence to the full course of PEP drugs and should have no further exposures to HIV while taking PEP.

What is PEP?

PEP consists of a combination of three HIV medications that an HIV-negative person takes for four weeks to reduce their risk of getting HIV after a potential exposure to HIV. This is different from pre-exposure prophylaxis (PrEP), which involves taking HIV medication on an ongoing basis, starting before and continuing after an exposure to HIV. PEP should be started as soon as possible, but definitely within 72 hours of being exposed to HIV. The prescription drugs used for PEP need to be taken every day for four full weeks (28 days).

How does PEP work to help prevent HIV?

PEP interferes with the pathways that HIV uses to cause a permanent infection in the body. For HIV to cause infection the virus must enter the body, infect certain immune cells, make copies of itself (replicate) within these immune cells, then spread throughout the body.

When PEP is taken, the HIV drugs get into the bloodstream and the genital and rectal tissues. If there is HIV in the body, the drugs can prevent HIV from replicating within the body’s immune cells, and help to prevent a permanent infection from developing.

PEP drugs need to start working against HIV as soon as possible after the virus enters the body, meaning that PEP should be started as soon as possible after a potential exposure and not more than 72 hours afterwards. Drug levels must also remain high during the month of treatment to help prevent infection. If the pills are not taken consistently, as prescribed, there may not be enough medication in the body to prevent HIV infection. 

When is PEP used?

PEP can be used by people who are HIV negative to prevent getting HIV after a potential exposure to HIV. It is meant to help prevent HIV transmission from a single accidental exposure.

PEP can be used after a potential exposure to HIV through sex or injection drug use. This can include having sex without using any HIV prevention method (such as a condom or PrEP), having a condom break during sex or sharing equipment used to inject drugs. It can also include experiencing a sexual assault. 

PEP can also be used after a potential exposure to HIV at work, such as when a healthcare worker or emergency responder has an accidental needle-stick injury.

What is the evidence for the effectiveness of PEP?  

The effectiveness of PEP in reducing HIV transmission risk has not been evaluated in randomized controlled trials, which are generally considered to produce the highest quality evidence. However, observational research has been conducted and this suggests that PEP can reduce the risk of getting HIV by more than 80%. Effectiveness is likely much higher than 80% if PEP is used consistently and correctly, as prescribed. This includes:

  • Obtaining PEP from a healthcare provider.
  • Taking the medications every day for 28 days. High adherence to the full month-long course of PEP is important for maximizing effectiveness.
  • Starting PEP as soon as possible after a potential exposure to HIV, ideally within 24 hours, and not more than 72 hours afterwards. The sooner PEP is started after an exposure to HIV the more likely it is to work because the drugs need to start interrupting HIV replication as soon as possible.
  • Taking extra precautions (for example, using condoms) to reduce the risk of being exposed to HIV again while taking PEP. The use of PEP is meant to reduce the risk from a single exposure to HIV and should only be used for emergencies.

The timing of PEP initiation after an HIV exposure is a key determinant of its effectiveness. The Canadian guideline recommends starting PEP as soon as possible, and up to a maximum of 72 hours after exposure to HIV. The evidence supporting the early initiation of PEP is primarily from animal studies. One study in macaques demonstrated that PEP initiated 12 hours and 36 hours post-exposure to HIV was more effective compared to 72 hours after exposure.  Animal studies also suggest that PEP effectiveness diminishes if the full course is not taken as directed (i.e., every day for 28 days).

Who should consider taking PEP?

An HIV-negative person who thinks they may have been exposed to HIV within the last 72 hours should consider taking PEP. When a person presents for PEP at a clinic or emergency room, a risk assessment will determine whether PEP should be started based on their risk for HIV infection. Assessment of HIV risk is based on the type of exposure and the likelihood that the contact person was HIV positive.

PEP may not be recommended if a person’s chance of getting HIV is low, either because their exposure carries no risk or very low risk of transmission (for example, oral sex) or because it is unlikely that the contact person is HIV positive. 

PEP is not intended for people with ongoing exposures to HIV. People who engage in high-risk behaviours on a regular basis, or who find themselves using PEP frequently, should consider using PrEP to prevent HIV instead.

What is involved in taking PEP?

First, a healthcare provider will assess whether the risk of HIV transmission is high or low, using the risk assessment described above. If the risk is high enough, PEP will be prescribed.

PEP should only be used by people who are HIV negative. When a person starts PEP, an HIV test will be done to determine their HIV status. If the person tests positive they should be referred to HIV care and treatment.

If rapid HIV testing (which gives results within a matter of minutes) is not available, the test result may not be ready for one to two weeks; however, PEP will be started immediately. PEP will be discontinued if the PEP user tests HIV positive, or if the contact person is confirmed to be HIV negative.

PEP medications need to be taken consistently and correctly—every day for four weeks—or the risk of HIV infection will increase. A counsellor, doctor, nurse, pharmacist or staff member at a community-based  organization can suggest strategies to help a person adhere to the pill-taking schedule and/or manage any side effects of the drugs.

A person taking PEP needs monitoring for side effects and other complications such as drug toxicity, though this is rare. Blood tests may be needed to ensure that the medications are not causing harm to the body. If side effects and toxicity are a problem, a healthcare provider may decide to change one or more of the drugs being used for PEP.

A person taking PEP should take extra precautions to avoid exposure to HIV while taking PEP. The use of PEP is only intended to reduce the risk of infection associated with one exposure. If a person continues to engage in behaviours that can transmit HIV, such as sharing needles or having unprotected sex, while taking PEP, their risk of getting HIV increases.

What are some of the safety concerns associated with taking PEP?

Drug resistance

A person with low adherence to PEP, who acquires HIV while taking PEP, could develop resistance to the drugs in PEP. If a person’s HIV becomes resistant to the PEP drugs, those same HIV drugs may not work for treating their HIV.

Side effects

HIV drugs can cause side effects, such as nausea, fatigue and diarrhea. The nature and severity of the side effects depend on the type of drugs prescribed and the person who is taking them. The HIV drugs that are recommended for PEP in Canada are generally well tolerated and associated with minimal side effects.

How can people access PEP?

The Canadian PEP guidelines recommend that PEP should be readily available in places where it is likely to be needed urgently. These include emergency departments, sexual health clinics and other clinics serving populations at increased risk of HIV.

The decision to provide PEP lies with the healthcare provider and is made on a case-by-case basis. The Canadian guidelines outline practical advice for physicians providing PEP, including how to assess risk in people who present for PEP, how to provide monitoring and follow-up, and recommended drug regimens.

People starting PEP may be offered a “starter pack” of pills, so that PEP can be started right away, along with a prescription that needs to be filled to receive the full 28-day course of medications. Most (but not all) emergency departments will have PEP “starter packs” available.

PEP is meant to be used for emergencies and should not be used as an ongoing HIV prevention strategy. People who may be exposed to HIV on a regular basis, or who find themselves using PEP frequently, might consider using PrEP to prevent HIV instead. However, there is an approach called PEP-in-pocket (also called PIP) that is recommended for people who recognize that they are sometimes at risk for HIV but not enough for them to want to take PrEP on an ongoing basis. PIP involves providing a person with a PEP prescription, before any exposure has occurred, so that they can obtain PEP medications quickly if needed after a potential exposure to HIV. Anyone using PIP should be counselled to start the medications and seek medical care as soon as possible after an exposure.

Anti-HIV drugs are expensive: a month-long course of PEP can cost $900 or more, depending on the drugs used. 

 If the potential exposure happened while working, PEP is usually covered. PEP is covered by some public and private health insurance plans after a potential exposure through sexual and drug use activities. However, this varies by province or territory and can also vary depending on the type of exposure (e.g., sexual assault versus consensual sex). PEP is often covered if it is necessary after a sexual assault.

Client resources

PEP: Preventing HIV after a potential exposure – booklet

PEP: Preventing HIV after a potential exposure - video

Service provider resources

The efficacy of post-exposure prophylaxis (PEP) for HIV – Ontario HIV Treatment Network

Canadian guideline on HIV pre- and postexposure prophylaxis: 2025 update  HIV Post-Exposure Prophylaxis (PEP) Guidelines – British Columbia Centre for Excellence in HIV/AIDS

Alberta guidelines for post-exposure management and prophylaxis: HIV, Hepatitis B, Hepatitis C and sexually transmitted infections –  Alberta Health Services

Guide pour la prophylaxie et le suivi après une exposition au VIH, au VHB et au VHC – Ministry of Health and Social Services of Quebec

References

  1. Tan DHS, Hull MW, Onyegbule SO, et al. Canadian guideline on HIV pre-and postexposure prophylaxis: 2025 update. CMAJ. 2025; December 1;197(41):E1374-91. Available from: https://www.cmaj.ca/content/197/41/E1374
  2. Centers for Disease Control and Prevention, U.S. Department of Health and Human Services. Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV – United States, 2016. Available from: https://stacks.cdc.gov/view/cdc/38856
  3. Bryant J, Baxter L, Hird S. Non-occupational postexposure prophylaxis for HIV: a systematic review. Health Technology Assessment. 2009 Feb;13(14):1–60.
  4. Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. New England Journal of Medicine. 1997;337(21):1485–1490.
  5. Beymer MR, Kofron RM, Tseng CH, et al. Results from the post-exposure prophylaxis pilot program (P-QUAD) demonstration project in Los Angeles County. International Journal of STD & AIDS. 2018 May;29(6):557-562.
  6. O’Byrne P, MacPherson P, Orser L. Nurse-led HIV PEP program used by men at high risk for HIV seroconversion. Journal of the Association of Nurses in AIDS Care. 2018;29(4):550-559.
  7. McDougal SH, Alexander J, Dhanireddy S, et al. Non-occupational post-exposure prophylaxis for HIV: 10-year retrospective analysis in Seattle, Washington. PLoS ONE. 2014;9(8):e105030.
  8. Beymer MR, Bolan RK, Flynn RP, et al. Uptake and repeat use of postexposure prophylaxis in a community-based clinic in Los Angeles, California. AIDS Research & Human Retroviruses. 2014;30(9):848-55.
  9. Whitlock G, McCormack C, Fearnley J, et al. High incidence in men who have sex with men attending for postexposure prophylaxis: A service evaluation. Sexually Transmitted Infections. 2017;93(3):214-216.
  10. Jain S, Oldenburg CE, Mimiaga MJ, et al. Subsequent HIV infection among men who have sex with men who used non-occupational post-exposure prophylaxis at a Boston community health centre: 1997-2013. AIDS Patient Care and STDs. 2015;29(1):20-25.
  11. Heendeniya A, Bogoch II. HIV prevention with post-exposure prophylaxis-in-pocket. The Lancet Public Health. 2019 Oct 1;4(10):e494.
  12. Otten RA, Smith DK, Adams DR, et al. Efficacy of postexposure prophylaxis after intravaginal exposure of pig-tailed macaques to a human-derived retrovirus (human immunodeficiency virus type 2). Journal of Virology. 2000 Oct;74(20):9771-5. 
  13. Whitney JB, Hill AL, Sanisetty S, et al. Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys. Nature. 2014 Aug 7;512(7512):74-7. 

 

Author(s): Arkell C, Harrigan M.

Updated: 2026