PrEP Side Effects: Oral Pills & Injectables Compared

Considering PrEP? Here's what to expect when it comes to side effects

Whether you're ready to start PrEP or just curious about how injectable and oral options stack up, you've probably wondered about side effects.

While most people using PrEP report mild or no side effects at all, some people do, so it’s helpful to know what might come up. This guide breaks down the most common and rare side effects of PrEP, especially Yeztugo side effects, the newest injectable option containing lenacapavir.

A quick heads-up: everyone reacts differently to medication. This article is a general guide, not a complete list of all possible side effects and reactions. If you have questions about how a medication could affect you, talk to a healthcare provider.

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The most common PrEP side effects, no matter the type 

Whether you’re considering oral PrEP such as Truvada or Descovy or the newer injectable options like Apretude and Yeztugo, some side effects show up more often than others. These are typical of antiretroviral medications.

Most common side effects of PrEP:

• Headache
• Nausea
• Fatigue
• Diarrhea

These reactions are typically mild and tend to resolve in a few days or weeks. Many people don’t notice them at all. 

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Oral PrEP: Side effects of Truvada and Descovy

Daily oral PrEP has been around longer than injectable options. If you’ve been on PrEP before, there’s a good chance you’ve used either Truvada or Descovy. Both are taken once daily and are highly effective at preventing HIV when used consistently.

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Truvada side effects

Truvada is the most commonly prescribed form of PrEP. It’s well-studied and has helped millions of people stay protected. Like other forms of PrEP, it can cause mild side effects like nausea or headaches.

In rare cases, Truvada has been linked to:

• Liver or kidney issues
• Bone density loss
• Lactic acidosis (a buildup of acid in the blood)
  

These side effects are uncommon and often reversible if you stop taking the medication. Your healthcare provider may do occasional lab work to monitor kidney or liver function while you’re on PrEP.

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Descovy side effects

Descovy is similar to Truvada in effectiveness but may have fewer long-term risks. It hasn’t been linked to bone density loss and is often considered a gentler option for your kidneys.

It can still cause the usual mild side effects (nausea, headache), and like Truvada, it requires occasional lab monitoring.

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Injectable PrEP: Side effects of Yeztugo and Apretude 

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Injectable PrEP is a newer type of PrEP that is effective at preventing HIV with just one dose every few months.

There are two types of injectable PrEP available today:

• Yeztugo (lenacapavir) — one dose every six months
• Apretude (cabotegravir) — one dose every two months

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Yeztugo (lenacapavir) side effects

Yeztugo is the newest long-acting injectable PrEP option, approved by the FDA in June 2025. It contains lenacapavir, a drug that’s also used in HIV treatment under the name Sunlenca.

Like many injectable medications, some people report experiencing discomfort at the injection site, including pain, irritation, or swelling after getting the shot. 

Lenacapavir side effects appear to be minimal based on clinical trials for Yeztugo, but research is ongoing.

One unique thing about the side effects of Yeztugo: after your injection, you might notice a small, firm, painless bump where the shot was given. Yeztugo is administered only twice per year, and that hard bump contains the medication that releases into your body over time.

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Apretude (cabotegravir) side effects

Apretude was the first injectable PrEP option approved and has been in use for several years.

It shares the usual injection site reactions like swelling, pain, or irritation. These typically lessen after your first few doses as your body adjusts.

In rare cases, Apretude has been linked to more serious side effects, including:

• Liver problems
• Mood changes or depression

These are uncommon but worth watching for. If you notice any major changes in your mood or discomfort that doesn’t go away, check in with your provider.

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Which PrEP option has the fewest side effects?

Based on current data, Yeztugo has the fewest documented side effects among all PrEP options. It’s discreet, long-acting, and hasn’t shown any serious complications so far.

But keep in mind: Yeztugo is new. That means we don’t have long-term data yet, and rare side effects may emerge over time.

Oral PrEP options like Truvada and Descovy are well-studied and reliable, and most people who take them don’t experience any ongoing or serious side effects.

The right option for you depends on your body, your lifestyle, and what feels easiest to stick with.

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What should I do if I experience side effects?

Most PrEP side effects are manageable and temporary. But if something feels wrong or doesn’t go away, don’t ignore it.

Here’s what to do:

• Keep track of your symptoms
• Reach out to your provider (or the Freddie team)
• Ask if switching meds could help
• Don’t stop taking PrEP without a backup plan
  

Sometimes switching to a different version of PrEP can make a big difference. And if you need to, it’s OK to pause or stop PrEP. You’ve got options.

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PrEP should work with your body, not against it

PrEP side effects are real, but they’re also typically mild and short-lived. What matters most is finding a version of PrEP that feels right for you: one that fits your life, protects your health, and gives you peace of mind.

Whether you’re curious about the new injectable meds or happy with your daily pill, you deserve care that meets you where you are.

You can book a free appointment with a Freddie clinician to discuss your options for PrEP.

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