Truvada Side Effects: What to Expect and When to Call Your Doctor

Like all medications, Truvada (emtricitabine/tenofovir disoproxil fumarate) can cause side effects. Most people tolerate it well, especially when using it for PrEP (HIV prevention). However, there are some important things to know — including two FDA boxed warnings — before you start this medication. This guide gives you an honest, clear picture of what to expect.

FDA Boxed Warnings: What You Must Know First

Truvada carries two FDA boxed warnings — the most serious type of drug warning. These are not common side effects, but they are serious enough that the FDA requires them to be prominently highlighted.

Worsening of hepatitis B (HBV) upon stopping Truvada: Because Truvada has anti-HBV activity, patients with chronic hepatitis B can experience a severe flare of their hepatitis when they stop taking Truvada. This can cause serious liver damage. If you have hepatitis B, your doctor must monitor your liver function closely for at least several months after stopping. Do NOT stop Truvada abruptly without talking to your doctor first.

HIV drug resistance risk in PrEP use: If you already have HIV infection (even if you don't know it), taking Truvada alone for PrEP can cause the HIV virus to develop resistance to the medication. This is why you must test HIV-negative immediately before starting PrEP, and every 3 months while on it.

Common Side Effects (Usually Mild and Temporary)

Most people starting Truvada experience few or mild side effects. The most common ones, especially in the first few weeks, include:

Nausea: Often improves over time; taking Truvada with food can help reduce nausea

Headache: Common in the first few weeks of use; typically mild

Diarrhea: GI symptoms are the most frequently reported side effects in PrEP trials

Abdominal pain: More common in the first month of therapy

Fatigue: Tiredness or low energy, especially when starting the medication

Dizziness: Occasionally reported, usually mild

In HIV-uninfected PrEP trial participants, headache and abdominal pain were the side effects reported more than 2% more frequently than placebo. For most patients, these effects are tolerable and improve with time.

Serious Side Effects: Less Common but Important to Know

Serious side effects from Truvada are uncommon, especially in HIV-negative patients using it for PrEP. However, you should know the warning signs:

Kidney problems (renal impairment): The TDF component of Truvada can affect kidney function. Signs include decreased urination, swelling in legs or ankles, unusual tiredness, or increased thirst. Baseline and periodic kidney function tests are required. Truvada should not be used for PrEP if your creatinine clearance is below 60 mL/min.

Fanconi syndrome: A rare but serious kidney tubule disorder that can cause excessive excretion of glucose, phosphate, and other nutrients, leading to bone problems and muscle weakness

Bone mineral density loss: Long-term TDF use is associated with modest decreases in bone density. In HIV-negative PrEP users, bone density typically returns to pre-treatment levels after stopping Truvada. HIV-positive patients on TDF may have greater bone effects. Report persistent bone pain or fractures to your doctor.

Lactic acidosis: A rare but potentially life-threatening buildup of lactic acid in the blood. Symptoms include severe stomach pain, nausea and vomiting, unusual muscle pain, feeling cold, dizziness, fast or uneven heartbeat, or trouble breathing. Call 911 if you experience these symptoms.

Liver problems (hepatotoxicity): Signs include yellowing of skin or eyes (jaundice), dark urine, severe stomach pain, or unusual tiredness. Seek medical attention promptly.

Immune reconstitution syndrome (HIV treatment patients): When starting HIV treatment, a strengthened immune system can cause inflammation around previously dormant infections. Report any new symptoms of infection after starting treatment.

Skin Darkening (Hyperpigmentation)

Hyperpigmentation (skin darkening on the palms of hands and soles of feet) has been noted in pediatric patients receiving emtricitabine (a component of Truvada). It is generally cosmetic and not a sign of serious harm, but should be mentioned to your doctor.

When Should You Call Your Doctor?

Call your doctor if you experience any of the following while taking Truvada:

Yellowing of skin or eyes, dark urine, or severe stomach/abdominal pain (possible liver problem)

Decreased urination or leg/ankle swelling (possible kidney problem)

Persistent bone or joint pain (possible bone density issue or Fanconi syndrome)

Nausea or vomiting that doesn't improve after the first few weeks

New or worsening symptoms of infection (especially if you're HIV-positive starting treatment)

Call 911 immediately if you have symptoms of lactic acidosis: severe abdominal pain, fast or irregular heartbeat, unusual muscle weakness, cold/blue skin, or extreme difficulty breathing.

The Big Picture on Truvada Safety

Truvada has been used by millions of people since 2004. For HIV-negative PrEP users, the risk profile is well-documented and generally favorable — mild GI side effects are the most common issue, and the serious risks (particularly kidney and bone effects) are significantly lower than in HIV-positive patients. The benefits of preventing HIV infection consistently outweigh these risks for eligible patients. Talk to your prescriber about your individual risk factors, and see our guide on Truvada Drug Interactions to know what medications to avoid.