PrEP Side Effects: What to Actually Expect

The Big Picture

Across all clinical trials and real-world data, PrEP has an excellent safety profile. The vast majority of people who start PrEP experience no side effects at all. Those who do experience side effects typically report mild symptoms that resolve on their own within the first few weeks. Fewer than 1% of people in clinical trials stopped PrEP due to side effects.

Side Effects by Medication

Descovy (emtricitabine/tenofovir alafenamide)

Common (first few weeks): Diarrhea, nausea, headache, fatigue, and abdominal pain. These are generally mild and resolve quickly. Just 1% of clinical trial participants stopped Descovy due to side effects.

Rare but monitored: Descovy can affect kidney function in some patients, though less so than Truvada. Your provider will check kidney function through blood tests every 3 months. Descovy may also cause slight increases in LDL cholesterol and triglycerides.

Weight: Some studies initially suggested Descovy might be associated with weight gain. More recent research indicates that Descovy users gain weight at roughly the same rate as the general population — and that Truvada may have a mild weight-suppressing effect, making the comparison misleading.

Generic Truvada (emtricitabine/tenofovir disoproxil fumarate)

Common (first few weeks): Nausea, diarrhea, headache, fatigue, vomiting, and stomach pain. About 10% of people experience some of these in the first month. Taking the pill before bed with food helps significantly.

Rare but monitored: Truvada can decrease kidney filtration capacity and reduce bone mineral density. Both effects are uncommon (less than 1% of patients), generally mild, and reversible when the medication is stopped. Your provider monitors kidney function and may check bone density if you have risk factors.

Hepatitis B note: If you have hepatitis B and stop taking Truvada or Descovy, you may experience a “flare” (worsening of hepatitis symptoms). Your provider should monitor you for several months after stopping.

Apretude (cabotegravir injection — every 2 months)

Common: Injection site reactions — pain, swelling, or hardness at the injection site. This is the most frequently reported side effect and occurs in the majority of patients. The discomfort typically decreases with each subsequent injection.

Less common: Headache, fever, fatigue, back pain, and muscle pain. Generally mild.

Yeztugo (lenacapavir injection — every 6 months)

Common: Injection site reactions (pain, swelling, nodules). Similar to Apretude but administered less frequently. In clinical trials, injection reactions were generally mild to moderate and decreased over time.

Less common: Nausea and headache. The overall side effect profile in trials was favorable, with 99.9% of participants remaining HIV-negative.

Descovy vs Truvada: Which Has Fewer Side Effects?

Descovy was developed specifically to reduce two of Truvada’s rare side effects: kidney function changes and bone density loss. Descovy uses a newer form of tenofovir (TAF) that delivers the drug more efficiently, resulting in lower blood levels and less kidney/bone impact.

In practice, the difference matters mainly for people with pre-existing kidney concerns or osteoporosis risk factors. For most healthy adults, both medications are well-tolerated with similar day-to-day side effect profiles (nausea, headache, fatigue in the first few weeks).

For a deeper comparison, see our Descovy vs. Truvada guide.

Tips for Managing First-Month Side Effects

Frequently Asked Questions

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