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PrEP can cause side effects, and the risks differ by medication. Early nausea, headache or stomach upset often improve. Oral tenofovir-based PrEP needs kidney monitoring; injectable PrEP commonly causes local reactions. Lenacapavir lumps can last for months. Tell your prescriber about severe, persistent or troubling symptoms so you can get appropriate care and a plan to maintain HIV protection.[2][4][5][7]
The common picture
HIV.gov describes PrEP as safe and reports reassuring experience over years of use. That broad reassurance does not mean every product has five years of follow-up or that serious adverse effects never occur. The medication-specific warnings and monitoring below still apply.[1]
The side effects that do occur are described the same way by both HIV.gov and CDC: some people taking PrEP may have nausea, diarrhea, headache, fatigue, and stomach pain, these side effects are usually not serious and go away over time, and you should tell your provider about any side effect that is severe, bothers you, or does not go away.[1][2]
In the iPrEx trial reported in the Truvada label, headache occurred in 7% of Truvada recipients versus 6% with placebo, abdominal pain in 4% versus 2%, and decreased weight in 3% versus 2%. These are results from that particular trial, not rates for every PrEP product or population.[3]
Truvada: kidney and bone monitoring
This is the part worth taking seriously rather than being frightened by. The Truvada label lists serious potential side effects including new or worsening kidney problems, up to kidney failure, and bone problems — bone pain, or softening or thinning of bones, which may lead to fractures — along with worsening of hepatitis B, lactic acidosis, and severe liver problems.[3]
Before starting PrEP, testing must confirm that you do not have HIV, and follow-up HIV testing remains essential. Kidney tests are required before and during oral tenofovir-based PrEP; cabotegravir does not require routine kidney assessments. CDC recommends kidney monitoring at least annually for everyone continuing oral PrEP, and at least every six months for people aged 50 or older or with starting creatinine clearance below 90 mL/min; other kidney risks may warrant closer checks.[4] Lenacapavir has its own HIV-testing and follow-up schedule.[6][2]
Descovy (emtricitabine/tenofovir alafenamide) is another daily oral option, but it is not indicated for prevention through receptive vaginal sex, regardless of gender identity. Kidney and bone history, exposure route, and other medicines help determine which PrEP option fits. People taking oral tenofovir-based PrEP should be screened for hepatitis B: stopping it when hepatitis B is present can trigger a liver flare.[4]
Injectables: what the shots feel like
In HPTN 083, 82% of participants receiving Apretude injections reported injection-site reactions versus 35% receiving placebo injections plus oral Truvada. In HPTN 084, the corresponding figures were 38% and 11%. The comparison groups also received injections; these figures do not mean Truvada tablets themselves caused injection-site reactions.[5]
Among the 2,117 people receiving at least one Apretude injection in HPTN 083, 3% discontinued because of injection-site reactions. No participant stopped for that reason in HPTN 084. Other reported adverse reactions included headache, nausea, diarrhea, fatigue and sleep disorders. Rare serious allergic reactions and liver problems are additional reasons to report concerning symptoms promptly.[5]
Lenacapavir (Yeztugo) is given every six months after initiation doses. Its common adverse reactions include local injection reactions, headache and nausea. Its HIV-testing schedule and drug-interaction checks should be reviewed with the prescriber.[7][6]
In the FDA safety populations, 2,140 people received Yeztugo in PURPOSE 1 and 2,183 in PURPOSE 2. Injection-site reactions occurred in 69% and 83%, respectively; most were mild or moderate. Discontinuation because of these reactions occurred in 0.2% and 1.2%. These safety denominators differ from the HIV-prevention efficacy analysis, and the proportion remaining HIV-negative is not a measure of tolerability.[7]
Pain and a persistent lump are different experiences. With Yeztugo, nodules were reported in 64% of PURPOSE 1 and 63% of PURPOSE 2 recipients; median durations after the first injections were 350 and 297 days. Do not expect every lump to disappear within days. Contact your clinic about worsening pain, spreading redness, drainage, fever or other concerning changes.[7]
What to actually do about side effects
Mild early stomach upset may improve over time. Ask your pharmacist about ways to manage it and whether taking your oral PrEP with food may help. You do not need to wait a month to report symptoms that bother you.[2]
If you want to stop or switch PrEP, contact your prescriber for a plan that covers ongoing HIV exposure and any hepatitis B treatment needs. Alternatives depend on your health, exposure route and access; a generic version has the same active medicines as its brand counterpart.[4][1]
Seek urgent care for symptoms of a serious reaction, such as difficulty breathing or a severe rash with fever. Do not continue a medicine through a suspected serious allergic reaction while waiting for a routine visit. Contact your prescriber promptly about other severe or persistent symptoms.[5][1]
Keep your follow-up visits. They help identify adverse effects and HIV infection promptly. Small tenofovir-related kidney changes often improve after stopping, but recovery is not guaranteed for every injury. Bone-density testing is considered when fracture history or other risk factors justify it; it is not a routine test required for every PrEP user.[3][4]
Related questions
Will PrEP damage my kidneys?
Tenofovir-based oral PrEP can affect the kidneys. Changes are usually small, but acute kidney failure and Fanconi syndrome have occurred. Baseline and follow-up tests help your clinician decide whether to continue, investigate a change or switch medication; they do not guarantee that every problem will be prevented. Cabotegravir does not require routine kidney monitoring.[3][4]
How long do PrEP side effects last?
Are the shots worse than the pills?
Pills and shots have different adverse-effect profiles. Apretude and Yeztugo commonly cause local reactions; both can also cause symptoms such as headache or nausea. Most trial injection reactions were mild or moderate, but some people stopped treatment because of them. Compare the options with your clinician rather than assuming shots are always easier to tolerate.[5][7]
Does PrEP affect fertility, weight, or mood?
Effects vary by product. For example, decreased weight was reported in 3% versus 2% with placebo in the Truvada iPrEx trial, and sleep disorders have been reported with Apretude. Discuss unexpected changes and fertility or pregnancy plans with your clinician. These trial findings do not establish the cause of an individual symptom or guarantee reproductive safety for every product.[3][5]
Related from RiseUpToHIV
References & Sources
- HIV.gov — Pre-Exposure Prophylaxis: general safety and reporting side effects. Source. ↩↩↩↩
- CDC — Preventing HIV with PrEP. Lists diarrhea, nausea, headache, fatigue, and stomach pain as side effects that usually go away, and requires an HIV test before starting plus routine follow-up visits. ↩ ↩ ↩ ↩ ↩
- FDA — Truvada prescribing information, 2024: iPrEx adverse reactions, kidney and bone precautions, hepatitis B warning. Source. ↩↩ ↩ ↩ ↩
- CDC HIV Nexus — Clinical Guidance for PrEP: oral kidney monitoring, exposure-route eligibility and hepatitis B precautions. Source. ↩ ↩ ↩ ↩ ↩ ↩
- FDA — Apretude prescribing information, April 2025: HPTN 083/084 safety populations, placebo injections and serious reaction warnings. Source. ↩↩↩ ↩ ↩ ↩ ↩
- CDC MMWR — Injectable lenacapavir PrEP recommendation, September 2025: dosing, safety and monitoring. Source. ↩ ↩
- FDA — Yeztugo prescribing information, June 2025: PURPOSE 1/2 safety denominators, adverse reactions and nodule duration. Source. ↩ ↩ ↩ ↩ ↩ ↩
Community publications like POZ, Positively Aware, and TheBody inform framing and lived-experience context on RiseUpToHIV. Every clinical, epidemiological, or public-health claim above is anchored to a primary source.