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

Apretude (cabotegravir extended-release injectable suspension) is generally well tolerated, but like any medication, it has a side effect profile you should know about before starting. The most important thing to understand: most common side effects are manageable and temporary, but a few serious ones require prompt medical attention.

The Most Common Side Effect: Injection Site Reactions

The most common side effect of Apretude is injection site reactions — affecting up to approximately 82% of patients in clinical trials. These typically include:

Pain or discomfort at the injection site (in the gluteal/buttock muscle)

Redness or bruising

Hardening or induration under the skin

Swelling or warmth

These reactions are typically mild to moderate, peak within 1-3 days after the injection, and resolve on their own within 1-2 weeks. Most patients report that injection site reactions improve over successive injections as their body adjusts. Warm compresses and over-the-counter pain relievers can help with discomfort.

Other Common Side Effects (Seen in At Least 1% of Patients)

According to FDA clinical trial data from studies HPTN 083 and HPTN 084, the following side effects were reported in at least 1% of patients receiving Apretude:

Headache

Pyrexia (fever)

Fatigue

Sleep disorders (insomnia)

Nausea

Diarrhea

Dizziness

Flatulence and abdominal pain

Vomiting

Muscle aches (myalgia)

Rash

Decreased appetite

Somnolence (drowsiness)

Back pain

Upper respiratory tract infection

Serious Side Effects: When to Call Your Doctor Right Away

These side effects are less common but require prompt medical attention:

Severe hypersensitivity reactions (call 911 or go to ER): Serious hypersensitivity reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported. Seek immediate care for: severe rash, rash with fever, blisters, mucosal involvement (oral sores), facial swelling, difficulty breathing, or angioedema.

Liver problems (hepatotoxicity): Hepatotoxicity has been reported. Contact your provider for: yellowing of skin or eyes (jaundice), dark urine, nausea/vomiting that won't stop, right-side abdominal pain, or unusual fatigue.

Depression and mood changes: Depressive disorders including major depression, persistent depressive disorder, and suicidal ideation or attempts have been reported. Contact your provider or a mental health crisis line immediately if you experience new or worsening depression, thoughts of self-harm, or significant mood changes.

The Unique Risk of Drug-Resistant HIV

Apretude carries a Boxed Warning about drug-resistant HIV. This is not a side effect in the traditional sense, but it's the most clinically significant risk: if Apretude is used by someone with undiagnosed HIV-1 infection, the virus can develop resistance to cabotegravir and other INSTI-class drugs. This is why HIV testing before EVERY injection is medically required.

Additionally, because cabotegravir persists in the body for up to 12 months after the last injection, if you acquire HIV during this tail phase (after stopping Apretude), the residual drug can still create resistance pressure. Always inform your provider if you think you may have been exposed to HIV after stopping Apretude.

Apretude During Pregnancy and Breastfeeding

There are insufficient human data on Apretude use during pregnancy to assess risk. Cabotegravir use in pregnancy should only occur when the expected benefit justifies the potential risk. A pregnancy registry (Antiretroviral Pregnancy Registry, APR) monitors outcomes — your provider can register you at 1-800-258-4263 if you become pregnant while using Apretude. Because Apretude can remain in the body for up to 12 months after the last injection, pregnancy exposure may occur even after stopping.

For information about medications that interact with Apretude, see our guide on Apretude drug interactions. If you need help finding a provider who administers Apretude, visit medfinder.com.