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Understanding PEP Side Effects, Plus Tips for Taking PEP

Medically reviewed by Barry S. Zingman, M.D.
Written by Emily Wagner, M.S.
Posted on October 31, 2022

Post-exposure prophylaxis (PEP) refers to medication that’s taken after a potential exposure to human immunodeficiency virus (HIV). This treatment helps people who are HIV-negative make sure they stay negative. PEP is meant for emergency use only and needs to be started as soon as possible — within 72 hours of exposure — to prevent HIV infection effectively.

What Is PEP?

PEP is a set of HIV medications that work quickly to prevent the virus from taking hold in your body. Specifically, these medications are antiretroviral treatments, which stop the virus from replicating (making more copies of itself). In human cells, DNA provides instructions for making RNA in a process known as transcription. RNA is then used for making proteins.

However, HIV carries its genetic code in RNA, which needs to be converted into DNA through a process known as reverse transcription. The virus uses a special enzyme — reverse transcriptase — to change RNA into DNA. Viruses that use RNA to make DNA are known as retroviruses, so the drugs used against them are called antiretrovirals.

The Centers for Disease Control and Prevention (CDC) recommends using one of two medication combinations for PEP:

  • Emtricitabine plus tenofovir alafenamide fumarate (Truvada) and raltegravir (Isentress)
  • Emtricitabine plus tenofovir and dolutegravir (Tivicay)

Emtricitabine plus tenofovir belongs to a class of medications known as nucleoside reverse transcriptase inhibitors (NRTIs). NRTIs block the enzyme reverse transcriptase, which prevents HIV from replicating.

Raltegravir and dolutegravir are integrase strand transfer inhibitors (INSTIs). These medications block the function of the integrase enzyme, which HIV uses to integrate (insert) its DNA into the DNA of immune cells. Blocking this enzyme stops HIV from replicating and inserting its genetic code into cells.

Why Take PEP?

PEP is used by people who have had a potential HIV exposure or don’t know the HIV status of a partner. Potential exposures include:

  • Unprotected sex with an HIV-positive person
  • Failed protection during sex (for example, a broken condom)
  • Sexual assault
  • Accidental needlesticks (such as when working in a health care setting)
  • Shared syringes, needles, or other equipment for injecting drugs

PEP should be used only in emergency cases. If you’re regularly exposed to someone with HIV (such as a sexual partner), you can talk to your health care provider about preexposure prophylaxis (PrEP). PrEP medications are taken daily for HIV prevention, as opposed to PEP, which shouldn’t be used regularly.

What Are the Side Effects of PEP?

In general, PEP medications are safe, but they may cause some side effects. Most are mild, but very rarely, the medication combos can lead to more serious conditions.

Tips To Manage Common PEP Side Effects

Mild side effects that typically occur when first starting PEP include an upset stomach and nausea, gas and bloating, headaches, and fatigue.

These side effects can usually be managed with over-the-counter (OTC) medications or at-home remedies. You might try these tips:

  • Take your PEP medication with food or before bed to help avoid nausea.
  • Snack on crackers or sip peppermint tea to settle your stomach.
  • Use an OTC gas remedy to combat gas or bloating.
  • Try taking a fiber supplement if you have loose stools.

Side Effects of Emtricitabine Plus Tenofovir

Rarely, emtricitabine plus tenofovir may cause serious side effects, including lactic acidosis. This condition develops when too much lactic acid builds up in the body. Symptoms include:

  • Unexpected muscle pain
  • Shortness of breath
  • Fatigue
  • Dizziness
  • Stomach pain accompanied by nausea and vomiting
  • Cold hands and feet, which may turn blue
  • An unusually fast heartbeat

If you have liver problems, some PEP medications may make them worse. Signs of liver problems that can occur while taking emtricitabine plus tenofovir include:

  • Dark urine
  • Jaundice (yellow appearance of skin and whites of eyes)
  • Nausea or vomiting
  • Lack of appetite for several days or more
  • Itching
  • Light-colored stools
  • Pain or tenderness on your abdomen’s right side

If you begin to notice symptoms of lactic acidosis or liver problems, let your health care provider know right away.

Side Effects of Raltegravir and Dolutegravir

Raltegravir and dolutegravir are generally well-tolerated but occasionally cause side effects, including rashes and allergic reactions. If you are taking these medications, contact your health care provider if you notice a rash along with any of these symptoms:

  • Malaise (feeling generally ill)
  • Fever
  • Fatigue
  • Achy muscles or joints
  • Sores or blisters in your mouth
  • Peeling or blistering skin
  • Difficulty breathing or swallowing
  • Swollen lips, tongue, mouth, throat, or face
  • Swollen or red eyes

Side effects can also occur when PEP drugs interact with other medicines. Before beginning PEP, it’s important to let your doctor know about all other medications that you take. That way, you and your health care provider can be aware of potential side effects or if a different PEP medication is needed.

How Is PEP Taken?

To be as effective as possible, PEP needs to be started within 72 hours (three days) of an exposure. If you think you’ve been exposed to HIV, call your health care provider immediately, or visit an emergency room or urgent care. A doctor will be able to evaluate your risk and prescribe PEP medications if needed.

One course of PEP lasts 28 days. Most PEP medications are taken once a day. It’s important to take every dose at about the same time every day so that the medication is as effective as possible. Missing a dose may put you at risk of developing HIV. Throughout your PEP course, your health care provider may have you come in for additional testing. At the end of the course, you’ll have follow-up appointments for repeat HIV tests to see if the medications worked.

Tips for Taking PEP Effectively

If you forget to take a PEP dose, take it as soon as you remember — but don’t double a dose to replace one you missed. Following these tips can help you stay on track with your PEP schedule:

  • Set an alarm on your phone to remind you to take your medication.
  • Keep your pill bottles in a spot that will keep you aware of them. (Note that the medications should be stored at room temperature — between 68 and 77 degrees Fahrenheit — in their original containers.)
  • Get in the habit of taking your medication after daily tasks, such as brushing your teeth or eating a meal.
  • Carry a few doses with you when traveling or if there’s a chance you could be away from home when it’s time for a dose.

Talk to Your Health Care Provider About PEP

If you believe you or your partner has been accidentally exposed to HIV, contact your health care provider or visit an emergency department right away to get help. PEP needs to be started as soon as possible and always within the first 72 hours after a possible exposure.

If HIV testing shows that you or your partner is positive, you might also talk to your provider about getting a PrEP prescription to help prevent an HIV-negative partner from becoming positive. Getting tested regularly for HIV and other sexually transmitted infections can help you and your partner stay safe.

Talk With Others Who Understand

On myHIVteam, the social network for people with HIV and their loved ones, more than 36,000 members come together to ask questions, give advice, and share their stories with others who understand life with HIV.

Are you or a loved one taking PEP? Share your experience in the comments below, or start a conversation by posting on your Activities page.

Posted on October 31, 2022
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Barry S. Zingman, M.D. specializes in HIV/AIDS medicine and general infectious disease. Review provided by VeriMed Healthcare Network. Learn more about him here.
Emily Wagner, M.S. holds a Master of Science in biomedical sciences with a focus in pharmacology. She is passionate about immunology, cancer biology, and molecular biology. Learn more about her here.

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