PrEP can cause temporary effects such as nausea, diarrhea, headache, fatigue, stomach discomfort, or pain where an injection was given. Many effects improve over time, but the possible effects depend on the medicine. Contact your prescriber or another health care provider if symptoms are severe, worsening, concerning, or do not go away. Do not stop or change PrEP without a clinician’s guidance.
This is general U.S.-focused information; recommendations and product labels may differ elsewhere.
Which PrEP medicine are you taking?
PrEP is available as oral medication and as injections. Side effects differ by product, so a symptom list for one form should not be assumed to describe another. CDC’s patient overview lists diarrhea, nausea, headache, fatigue, stomach pain, and injection-site pain as possible effects, and says they usually improve over time. CDC does not give a frequency for each symptom on that page, and not everyone will experience them. CDC: Preventing HIV with PrEP
Oral tenofovir-based PrEP
Oral PrEP can cause gastrointestinal symptoms and other effects, but frequencies depend on the specific medicine and study. For example, current Descovy labeling identifies diarrhea as the most common adverse reaction meeting the label’s 5% threshold in an adult PrEP trial; that figure is specific to Descovy and that trial, not a rate for all oral PrEP. DailyMed: Descovy labeling
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Cabotegravir injections
With cabotegravir, pain, tenderness, or swelling at the injection site are frequently reported. CDC describes them as generally mild or moderate and short-lived. An older CDC patient handout says local pain, redness, and swelling usually fade within a few days. CDC: Injectable cabotegravir patient handout
Lenacapavir injections
Lenacapavir is a subcutaneous PrEP option given every six months for eligible people under CDC’s 2025 recommendation. In the trials CDC summarized, the most common adverse events were mild-to-moderate injection-site reactions. CDC recommendation for injectable lenacapavir
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The U.S. DailyMed label provides a more detailed picture from PURPOSE 1, one lenacapavir trial. In that trial, 69% of participants receiving lenacapavir had an injection-site reaction: 50% had grade 1 and 19% grade 2 reactions. Four participants (0.2%) had grade 3 reactions, including an ulcer or nodule, and four (0.2%) discontinued because of injection-site reactions. Nodules were reported in 64%; their median duration after initial injections was 350 days (interquartile range 182–470), and median maximum diameter was 3.0 cm (interquartile range 2.0–3.5). These trial figures describe PURPOSE 1, not what an individual should expect, and the label cautions that adverse-event rates from different trials cannot be directly compared. DailyMed: lenacapavir labeling
In the same label, headache and nausea were reported in at least 5% of participants in at least one trial, with different rates by study: PURPOSE 1 reported headache in 7% and nausea in 5%; PURPOSE 2 reported headache in 2% and nausea in 2%. Those are trial-specific results, not a general rate for all PrEP.
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When should you contact a clinician?
CDC’s practical advice is to talk with a health care provider about side effects that are severe or do not go away. You should also seek advice if a symptom is worsening or concerning; there is no single duration threshold in the CDC guidance that applies to every symptom or medication. Do not wait out a severe reaction.
- For cabotegravir, contact your provider if injection-site pain, redness, or swelling is severe or persistent. The older CDC handout suggests an over-the-counter pain medicine or a heating pad on the site for 15–20 minutes a couple of times a day as possible comfort measures; ask a clinician or pharmacist whether an over-the-counter medicine is suitable for you.
- For lenacapavir, a lump can last longer than routine injection soreness: PURPOSE 1 reported long-lasting nodules. Ask your prescriber for advice about a lump, particularly if it is severe, worsening, ulcerated, or otherwise concerning. A lump alone is not enough to determine what is happening.
- If you have symptoms that could indicate a new HIV infection, seek prompt clinical assessment. PrEP follow-up includes HIV testing, and use of PrEP during an undiagnosed infection can contribute to drug resistance.
CDC clinical guidance for PrEP
What monitoring and medication warnings matter?
Some important risks are not reliably identified by how you feel. Oral tenofovir-based PrEP requires kidney-function assessment: CDC recommends baseline and periodic monitoring. Descovy labeling calls for assessment of serum creatinine, estimated creatinine clearance, urine glucose, and urine protein on a clinically appropriate schedule. Routine aches or fatigue cannot establish whether kidney function is normal or impaired. CDC clinical guidance for PrEP
Descovy and Truvada labeling also contain warnings that matter when starting, monitoring, or stopping treatment. Both include warnings about hepatitis B worsening after discontinuation in people with hepatitis B and resistance risk if used for PrEP during undiagnosed early HIV. Truvada labeling also warns about lactic acidosis and severe hepatomegaly. These are medication-specific warnings, not a list of routine effects to expect. Ask your prescriber before stopping or changing medication; a change or interruption may require a replacement prevention plan. DailyMed: Descovy labeling FDA: Truvada label (2025)
Independent reader supportYour contribution helps us test, update, and keep practical guides available for everyone.How to discuss a possible side effect
When you contact your prescriber, say which PrEP product you use, when the symptom began, whether it is getting better or worse, and whether it followed an injection or a change in medication. Your clinician can consider the medicine, timing, and required testing together. Do not skip doses, stop treatment, or switch products on your own; ask for a plan that keeps HIV prevention and any needed monitoring in view.
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