Postexposure prophylaxis (PEP) is a medication-based treatment you follow if you think you might have been exposed to the human immunodeficiency virus (HIV). You usually take PEP medication every day for 28 days to help prevent infection. PEP is designed for emergency situations, and you must start taking it within 72 hours of possible exposure for it to be most effective at preventing HIV infection. While PEP can be a powerful tool for protecting your health, it’s normal to have questions about possible side effects and how to manage them. This article will walk you through what you might experience while taking PEP and offer practical tips to help you feel more comfortable during your treatment.

What Is PEP?

PEP is a group of HIV medicines that act fast to stop the virus from taking hold in your body. These medicines are called antiretroviral treatments because they block the virus from making more copies of itself.

To understand how antiretroviral treatments work, first you need to understand how HIV works. A lot of the terminology and concepts can be difficult to understand, but it’s worth learning the basics. Inside our cells, DNA gives instructions to make RNA in a process called transcription, and then RNA helps build proteins. But HIV is different — it carries its genetic code in RNA. To use that RNA, the virus must turn it into DNA through a process called reverse transcription. HIV uses an enzyme called reverse transcriptase to change its RNA into DNA. Viruses that start with RNA and make DNA are called retroviruses. That’s why the drugs used against HIV are called antiretrovirals.

PEP is a kind of treatment, not a specific medicine. There are two possible combinations of medication for PEP that adults usually take, as long as they’re generally healthy:

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

Emtricitabine plus tenofovir belongs to a class of medications called nucleoside reverse transcriptase inhibitors (NRTIs). NRTIs block the enzyme reverse transcriptase, and this prevents HIV from making more copies of itself.

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 making copies of itself and inserting its genetic code into cells.

Sometimes, if these medications aren’t a good fit for a specific person, doctors may choose different medicines for PEP. These other options are picked to make sure the person can still get the protection they need against HIV, based on their health and any other medicines they take.

Why Take PEP?

People use PEP if they think they may have been exposed to HIV, or if they don’t know the HIV status of a partner. You can have a potential exposure in several ways, including through:

• 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 healthcare setting)
• Shared syringes, needles, or other equipment for injecting drugs

PEP should only be used in emergency cases. If you’re regularly exposed to someone with HIV (such as a sexual partner), you can talk to your healthcare provider about preexposure prophylaxis (PrEP). Although their names look similar, PrEP and PEP are very different. PrEP medications are taken daily for HIV prevention, as opposed to PEP, which you should only take in emergencies (if you believe you have been exposed to HIV).

What Are the Side Effects of PEP?

In general, PEP medications are safe, but they may cause some side effects. Most PEP medication side effects are mild, but very rarely, the medication combinations 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 (bowel movements).

Side Effects of Emtricitabine Plus Tenofovir

In rare cases, 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 (extreme tiredness that doesn’t improve with rest)
• 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 the right side of your abdomen

If you begin to notice symptoms of lactic acidosis or liver problems, tell your healthcare provider 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’re taking these medications, contact your healthcare 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 you start a PEP treatment, it’s important to let your doctor know about all other medications that you take. That way, you and your healthcare provider can be aware of potential side effects, or you can figure out if you need a different PEP medication. There is little evidence that long-term side effects of PEP are common, since the treatment only lasts 28 days — but it’s still important to let your doctor know how you’re feeling.

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 healthcare provider immediately, or visit an emergency room or urgent care. A doctor will be able to evaluate your risk and prescribe PEP medications if you need them.

One course (full treatment) of PEP lasts 28 days. Some PEP medications are taken once a day, but others need to be taken twice a day. Your doctor will let you know how often to take your medicine. 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 increase your risk of developing HIV. Throughout your PEP course, your healthcare 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.

What Happens After PEP Treatment?

After finishing postexposure prophylaxis (PEP) treatment, you’ll need to follow up with your healthcare provider for additional HIV testing — usually at four to six weeks, three months, and sometimes six months after exposure. These follow-up visits help your doctor confirm whether the PEP was effective and monitor for side effects. If you’re still at risk of developing HIV, your doctor might discuss starting preexposure prophylaxis (PrEP) for ongoing prevention. Most people experience few or mild post-exposure prophylaxis side effects, and completing all follow-up appointments is important for your health.

Talk to Your Healthcare Provider About PEP

If you believe you or your partner has been accidentally exposed to HIV, contact your healthcare 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, members come together to ask questions, give advice, and share their stories with others who understand life with HIV.

Have you ever needed to take PEP? Share your experience in the comments below, or start a conversation by posting on your Activities page.