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Post-Exposure Prophylaxis (PEP): How It Works and When to Start

6 days ago
5 min read

Updated: 2 days ago

Written and medically reviewed by Dr. Baraa Alnahhal, MD · Last reviewed: November 2026 · How we review

Quick Answer

Post-exposure prophylaxis (PEP) is a short course of HIV medicines taken after a possible exposure to HIV to keep the virus from taking hold. You must start within 72 hours, the sooner the better, and take the pills every day for 28 days. Treat any possible HIV exposure as an emergency and get care right away.

What the research says

  • Early treatment after a needlestick lowered HIV risk: in a study of health workers exposed to HIV through needlesticks, the average infection risk per exposure was 0.3%, and taking an HIV medicine afterward was linked to about 81% lower odds of infection (Cardo DM et al., N Engl J Med, 1997) [2]

  • Many people don't finish PEP: across 97 studies of 21,462 PEP courses, only about 57% of people finished all 28 days, and completion was lowest after sexual assault (40%) and in teens (37%) (Ford N et al., AIDS, 2014) [3]

Key takeaways

  • PEP is emergency HIV prevention after a possible exposure.

  • Start within 72 hours; sooner is better.

  • Take it every day for 28 days.

  • It lowers HIV risk by more than 80%.

  • PEP isn't for ongoing protection; ask about PrEP for that.

What is PEP?

PEP uses antiretroviral medicines, the same kinds used to treat HIV, to stop the virus from copying itself before an infection becomes permanent. Once HIV takes hold, it's a lifelong condition, so starting PEP quickly matters. PEP is different from PrEP (pre-exposure prophylaxis), which people at ongoing risk take before any exposure. Sources: [1]

When PEP is used

When to get PEP: sex without a condom or a broken condom, sexual assault, sharing needles or drug equipment, a needlestick or other exposure at work

Start PEP within 72 hours; sooner is better.

  • Vaginal or anal sex without a condom, or a condom that broke, with someone who has or may have HIV.

  • Sexual assault.

  • Sharing needles or other drug equipment.

  • A needlestick or other exposure to blood at work. Sources: [1]

PEP usually isn't recommended if more than 72 hours have passed, if you already take PrEP consistently, or if the risk is very low, such as oral sex or contact with saliva, sweat or tears. Sources: [1]

PEP medicines

Part of regimen

Options

Backbone (two drugs in one pill)

Emtricitabine with tenofovir (Truvada or Descovy)

Third drug

Dolutegravir (Tivicay). A preferred all-in-one option is bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy), one pill a day

Depending on the drugs, you take them once or twice a day. Your provider may adjust them for other health conditions. Sources: [1]

How to take PEP

How PEP works: get care within 72 hours, have baseline blood tests, take the pills every day for 28 days, use condoms during treatment, get follow-up HIV tests at 4 to 6 weeks, 12 weeks and 24 weeks

PEP lowers HIV risk by more than 80%.

  1. Go to an emergency room, urgent care, sexual health clinic or a provider who prescribes PEP as soon as possible.

  2. Get blood and urine tests for HIV, hepatitis B and C, pregnancy, and kidney and liver function; you may be tested or treated for other STIs.

  3. Start PEP within 72 hours of exposure.

  4. Take every dose, every day, for 28 days.

  5. Use condoms during sex until you know your HIV status. Sources: [1]

Missing doses or stopping early raises your risk of infection. Set reminders and ask your provider what to do if you miss a dose. Sources: [1, 3]

Side effects

Side effect

What helps

Nausea, vomiting or diarrhea

Ask which over-the-counter medicines are safe

Tiredness

Rest; usually mild

Headache

Over-the-counter pain relievers if your provider approves

Side effects are usually mild and manageable. Don't stop PEP because of side effects without talking to your provider. Sources: [1]

Follow-up testing

PEP follow-up timeline: start within 72 hours, take pills for 28 days, HIV test at 4 to 6 weeks, HIV test at 12 weeks, final HIV test at 24 weeks

Retest for other STIs at 4 to 6 weeks after sexual exposure.

When

Test

4 to 6 weeks after exposure

HIV test; STI tests after sexual exposure

12 weeks

Final HIV test (lab antigen/antibody test plus HIV RNA test)

Work-related exposure

Your provider may advise a different schedule

Sources: [1]

How well PEP works

Studies suggest PEP lowers the risk of HIV by more than 80%. It works less well if you start late, miss doses, don't finish all 28 days, are exposed again during treatment or the virus is resistant to the drugs. If you're often at risk, ask your provider about PrEP and regular STD testing. Sources: [1, 2]

Where to get help

  • Treat a possible HIV exposure as a medical emergency.

  • Go to an emergency room, urgent care, sexual health clinic or a provider who prescribes PEP.

  • After sexual assault, ask for a sexual assault nurse examiner; most emergency departments have one.

  • Seek care even if more than 72 hours have passed, since you may still need testing and support. Sources: [1]

Conclusion

PEP is a safe, effective way to prevent HIV after a possible exposure, but timing is everything. Get care within 72 hours, take every dose for 28 days and complete your follow-up tests.

Keep learning: read about HIV and AIDS and sexually transmitted infections.

Frequently asked questions

What is PEP?

A 28-day course of HIV medicines taken after a possible exposure.

How soon do I need to start PEP?

Within 72 hours; the sooner, the better.

How long do I take PEP?

Every day for 28 days.

How effective is PEP?

Studies suggest it lowers HIV risk by more than 80%.

What's the difference between PEP and PrEP?

PEP is taken after an exposure; PrEP is taken before, for ongoing protection.

What are the side effects?

Usually mild nausea, tiredness, diarrhea or headache.

Where can I get PEP?

An emergency room, urgent care, sexual health clinic or a provider who prescribes it.

What if I miss a dose?

Take it as soon as you can and ask your provider; missed doses lower protection.

Do I need HIV tests afterward?

Yes, usually at 4 to 6 weeks and a final test at 12 weeks. Work-related exposures may follow a different schedule.

Can I take PEP after more than 72 hours?

It usually isn't recommended, but still get care and testing.

Related Reading

Protease Inhibitors: Types, How They Work and Side Effects explains protease inhibitor medicines.

References

  1. Cleveland Clinic. Post-Exposure Prophylaxis (PEP): Benefits & Side Effects. Cleveland Clinic. Last updated September 28, 2023. https://my.clevelandclinic.org/health/treatments/post-exposure-prophylaxis

  2. Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. N Engl J Med. 1997;337(21):1485-1490. PMID 9366579. https://doi.org/10.1056/NEJM199711203372101

  3. Ford N, Irvine C, Shubber Z, et al. Adherence to HIV postexposure prophylaxis: a systematic review and meta-analysis. AIDS. 2014;28(18):2721-2727. PMID 25493598. https://doi.org/10.1097/QAD.0000000000000505

Medical disclaimer

This article is for general education only and does not replace advice from a qualified healthcare professional. Talk to your doctor about your own diagnosis and treatment, and seek emergency care right away for severe or sudden symptoms.

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