PrEP can cause temporary effects such as nausea, diarrhea, headache, fatigue, stomach discomfort, or soreness where an injection was given. Many effects improve over time, but the symptoms depend on the specific medicine. Contact your prescriber or another health care provider about side effects that are severe or do not go away; do not stop or change PrEP without a clinician’s plan.
This is general U.S.-focused information. CDC guidance and U.S. product labeling may differ from recommendations where you live.
Which PrEP side effects are possible?
PrEP is available as oral medication and injections, and their side-effect profiles are not interchangeable. The CDC’s patient overview lists diarrhea, nausea, headache, fatigue, stomach pain, and injection-site pain as examples, and says these effects usually improve over time. It does not give a frequency for each symptom, and the list does not mean everyone taking PrEP will experience them. See the CDC overview of preventing HIV with PrEP.
Oral tenofovir-based PrEP
Oral products can cause gastrointestinal symptoms and other effects, but rates depend on the product and the study. For example, the current Descovy label identifies diarrhea as the most common adverse reaction meeting the 5% threshold in an adult PrEP trial; that is a product- and trial-specific result, not a rate for all oral PrEP. The Descovy U.S. prescribing information also calls for kidney-related assessments during use.
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Cabotegravir injections
With cabotegravir, pain, tenderness, or swelling near the injection site are frequently reported. CDC clinical guidance characterizes these reactions as generally mild or moderate and not long-lasting. An older CDC patient handout says mild or moderate pain, redness, and swelling often fade within a few days; it mentions an over-the-counter pain medicine or a heating pad applied 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, and contact your provider if the reaction is severe or persists. See CDC’s cabotegravir patient handout and CDC clinical guidance for PrEP.
Lenacapavir injections
Lenacapavir is a subcutaneous PrEP injection given every six months to eligible people under CDC’s 2025 recommendation. The trials summarized by CDC found that the most common adverse events were mild-to-moderate injection-site reactions. Its injection-site profile merits separate consideration: nodules may last substantially longer than ordinary short-lived soreness.
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In PURPOSE 1, 69% of participants receiving lenacapavir had an injection-site reaction: 50% had grade 1 reactions and 19% grade 2. Four participants (0.2%) had grade 3 reactions, including an ulcer or nodule, and four (0.2%) stopped treatment because of injection-site reactions. Nodules were reported in 64%; their median duration after initial injections was 350 days (interquartile range 182–470), and the median maximum diameter was 3.0 cm (interquartile range 2.0–3.5). These are results from that trial, not a forecast for an individual. The label cautions that adverse-event rates from different trials cannot be compared directly. The DailyMed lenacapavir label also reports headache and nausea in at least 5% of participants for some trial outcomes: in PURPOSE 1, headache was 7% and nausea 5%; in PURPOSE 2, each was 2%.
When should you contact a clinician?
CDC’s practical guidance is to talk with a health care provider about side effects that are severe or do not go away. Seek advice as well if symptoms are getting worse or concern you; CDC does not set a universal number of days that defines “persistent.” Do not wait out a severe reaction.
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- For cabotegravir, ask your provider about injection-site pain, redness, or swelling that is severe or does not settle as expected.
- For lenacapavir, contact the prescriber about a lump or other injection-site change that is severe, worsening, ulcerated, or otherwise concerning. Because trial nodules sometimes lasted a long time, a lump alone does not establish an emergency; your prescriber can advise based on the injection and your symptoms.
- If you have symptoms that could be related to a new HIV infection, contact a clinician promptly for assessment. PrEP requires HIV testing and follow-up, and using PrEP with undiagnosed HIV can contribute to drug resistance.
Why follow-up matters even when you feel well
Some important PrEP risks are not something you can reliably identify from how you feel. CDC recommends baseline and periodic kidney monitoring for oral tenofovir-based PrEP. Descovy labeling calls for assessment of serum creatinine, estimated creatinine clearance, urine glucose, and urine protein on a clinically appropriate schedule. Ordinary aches or fatigue alone do not show whether kidney function is normal or impaired.
Medication labels also contain specific warnings that should not be mistaken for routine side effects. Descovy and Truvada warn about severe worsening of hepatitis B after stopping in people with hepatitis B, and about drug resistance if taken as PrEP during undiagnosed early HIV. Truvada labeling also warns about lactic acidosis and severe hepatomegaly. Discuss symptoms, test results, and any concern about side effects with the prescriber before stopping or changing medication; stopping may require a prevention plan and, for some people, hepatitis B follow-up. See the Descovy label and Truvada U.S. label.
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, share the name of your PrEP medicine, when the symptom began, whether it is improving or worsening, and—if it followed an injection—where and when the injection was given. Mention other medicines or supplements and any missed doses. This information can help the clinician decide whether you need an examination, testing, symptom relief, or a change in your prevention plan.
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