What are the contraindications and cautions for using Cabotegravir (Apretude) for Pre-Exposure Prophylaxis (PrEP)?

Contraindications and Cautions for Cabotegravir (Apretude) PrEP

Absolute Contraindications

Cabotegravir is absolutely contraindicated in three specific situations that must be ruled out before initiating therapy. 1

• Positive HIV-1 status: Never initiate cabotegravir PrEP in anyone with confirmed HIV infection, as monotherapy will lead to rapid resistance development 1
• Previous hypersensitivity reaction to cabotegravir: Any prior allergic or hypersensitivity reaction to the drug precludes its use 1
• Concurrent use of potent enzyme inducers: Specifically carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, and rifapentine, which significantly reduce cabotegravir levels below protective thresholds 1

Critical Pre-Initiation Requirements

Before the first injection, comprehensive HIV testing including BOTH a fourth- or fifth-generation antigen/antibody test AND an HIV RNA test with lower limit of quantification ≤50 copies/mL is mandatory. 2, 3 This dual testing approach is essential because:

• Standard antibody tests alone can miss acute HIV infection 4
• Cabotegravir can delay HIV seroconversion and mask early infection, creating a phenomenon called LEVI (long-acting early viral inhibition) 2
• Starting cabotegravir in someone with undetected HIV leads to integrase inhibitor resistance 3

If clinical suspicion exists for acute HIV infection (fever, rash, lymphadenopathy, flu-like illness), do not initiate cabotegravir until HIV RNA results confirm negative status. 2

Important Cautions and Special Populations

Drug Interactions Requiring Dose Adjustment

• Rifabutin coadministration requires dose adjustment of rifabutin when used with cabotegravir 2
• All potent UGT1A1 inducers should be avoided as they reduce cabotegravir concentrations 2

Anatomical Considerations

• Use with caution in individuals with gluteal implants or fillers, as the intramuscular injection site may be compromised 2

Injection Site Reactions

• Injection site reactions occur in up to 81% of recipients but typically diminish over time 3, 5
• These are not contraindications but require patient counseling for adherence 6

Renal Considerations

• Baseline serum creatinine and estimated creatinine clearance are required before initiation 2
• Unlike tenofovir-based PrEP, cabotegravir actually causes less decrease in creatinine clearance, making it potentially advantageous in those with borderline renal function 6

Mandatory Baseline Testing Before First Injection

Beyond HIV testing, the following must be completed 2:

• Hepatitis B surface antigen (to identify those needing HBV treatment, not a contraindication to cabotegravir)
• Hepatitis C antibody
• Serum creatinine/estimated creatinine clearance
• Pregnancy test for individuals of childbearing potential
• STI screening (gonorrhea, chlamydia, syphilis)

Ongoing Monitoring Requirements

HIV testing must be repeated before EVERY subsequent injection using point-of-care rapid antibody test plus laboratory antigen/antibody test (RNA testing not routinely needed for follow-up unless breakthrough suspected). 2, 3

Common Pitfalls to Avoid

• Failing to perform HIV RNA testing at initiation: Antigen/antibody tests alone miss 10-15% of acute infections 2, 4
• Not having oral PrEP backup available: Patients need a 1-month supply of tenofovir-based oral PrEP for bridging if injections are delayed ≥7 days 3
• Missing drug interaction screening: Specifically asking about anticonvulsants, rifamycins, and herbal supplements that induce metabolism 1
• Inadequate counseling about injection site reactions: Setting expectations prevents discontinuation 5