What is Apretude (cabotegravir)?

Apretude: Long-Acting Injectable Cabotegravir for HIV Prevention

Apretude (cabotegravir) is a long-acting injectable HIV-1 integrase strand transfer inhibitor administered every two months for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in at-risk adults and adolescents weighing at least 35 kg (77 lbs). 1, 2

Mechanism and Formulation

Apretude works by preventing HIV-1 DNA integration into host cell DNA, thereby inhibiting viral replication 3. Key characteristics include:

• First long-acting injectable PrEP option approved by the FDA 3
• Extended-release injectable suspension allowing for infrequent dosing 3
• Superior efficacy compared to daily oral PrEP regimens in clinical trials 2
• Highly protein-bound (>99.8%) with a mean elimination half-life of 41 hours 1

Dosing Schedule

The recommended dosing schedule for Apretude is:

• Initial dose: 600 mg (3 mL) administered via gluteal intramuscular injection
• Second dose: 4 weeks after the first injection
• Subsequent doses: Every 8 weeks thereafter 2, 4

Patient Selection and Initiation

Before starting Apretude:

1. HIV testing is mandatory:

   • Confirm HIV-negative status with both rapid point-of-care HIV antibody test AND laboratory-based HIV antigen/antibody test 2
   • Ideally include an HIV RNA (viral load) test with a lower limit of quantification of ≤50 copies/mL 4
   • Do not start Apretude if HIV status is unclear or if symptoms of acute HIV infection are present 1

2. Additional screening:

   • Assess renal function (creatinine clearance ≥60 mL/min)
   • Screen for hepatitis B infection
   • Perform complete STI screening (gonorrhea, chlamydia, syphilis) 2

3. Oral lead-in consideration:

   • Optional oral cabotegravir lead-in (30 mg daily for 4-5 weeks) may be considered for patients with severe atopic histories or those who specifically request it
   • Not recommended for patients who struggle with daily oral medication adherence 2

Monitoring

Regular monitoring while on Apretude includes:

• HIV testing at each injection visit (rapid test and laboratory-based antigen/antibody test) 2
• STI screening every 4 months (every second injection) 2
• Liver function tests every 6 months 2
• Management of injection site reactions with topical/systemic analgesics and hot/cold packs 2

Efficacy and Advantages

Apretude has demonstrated superior efficacy to daily oral emtricitabine/tenofovir disoproxil fumarate in preventing HIV-1 acquisition in:

• Transgender women
• Cisgender men who have sex with men
• Cisgender women 3

Key advantages include:

• Convenient bimonthly dosing after initial loading doses
• Eliminates daily adherence challenges associated with oral PrEP
• Long-acting formulation ensuring continuous protection 3, 5

Important Considerations and Precautions

1. Missed doses:

   • Provide a 1-month supply of tenofovir-based oral PrEP for use if injections are delayed by ≥7 days
   • If injections are resumed ≥8 weeks late, "reloading" is recommended with two injections 4 weeks apart before returning to every-8-week dosing 2, 4

2. Drug interactions:

   • Do not use with potent UGT1A1 inducers
   • Avoid use with rifampin, rifapentine, carbamazepine, oxcarbazepine, phenobarbital, and phenytoin 1
   • Dose adjustment of rifabutin is recommended if coadministered 4

3. Special populations:

   • Use caution in patients with gluteal implants or fillers 4, 2
   • No dosage adjustment necessary for mild to moderate hepatic or renal impairment 1
   • Effect of severe hepatic impairment (Child-Pugh C) is unknown 1

4. Persistence in body:

   • Cabotegravir may persist in the body for up to 12 months after the last injection 2
   • For individuals stopping injectable PrEP but still needing HIV protection, transition to another form of HIV prevention is recommended 4, 2

Common Side Effects

The most common side effect is injection site reactions, occurring in up to 81% of clinical trial participants 5. These reactions typically diminish in severity over time 4.

Apretude represents a significant advancement in HIV prevention, offering an effective alternative to daily oral PrEP with the convenience of bimonthly injections, potentially improving adherence and effectiveness in real-world settings.