Apretude (Cabotegravir): Long-Acting Injectable HIV Pre-Exposure Prophylaxis
Apretude (cabotegravir) is the first long-acting injectable medication approved for HIV pre-exposure prophylaxis (PrEP), administered as gluteal intramuscular injections every 2 months after an initial loading phase, providing superior protection against HIV acquisition compared to daily oral PrEP options. 1, 2
Mechanism of Action and Formulation
- Cabotegravir is an HIV-1 integrase strand transfer inhibitor (INSTI) that prevents DNA integration and inhibits HIV-1 replication 3, 2
- Formulated as an extended-release injectable suspension with a long elimination half-life (approximately 40 days) that allows for infrequent dosing 3, 4
- Highly protein-bound (>99.8%) with slow absorption and extended release properties that maintain protective drug levels for weeks 3
Approved Indication
- Indicated for PrEP to reduce the risk of sexually acquired HIV-1 infection in at-risk adults and adolescents weighing ≥35 kg who have a negative HIV-1 test prior to initiation 2, 5
- Demonstrated superior efficacy to daily oral tenofovir disoproxil fumarate/emtricitabine in clinical trials across multiple populations including:
Dosing Schedule
- Administered as gluteal intramuscular injections at a dose of 600 mg (3 mL) 1, 7
- Dosing schedule:
- An oral lead-in period to establish tolerability is optional but not required 1
- If injections are delayed by 8 or more weeks (≥12 weeks from previous for injection 2, or ≥16 weeks from previous for injections 3+), "reloading" with two injections 4 weeks apart is recommended before returning to the every-8-week schedule 1, 7
Clinical Efficacy
- Phase 3 clinical trials demonstrated superior efficacy compared to daily oral tenofovir disoproxil fumarate/emtricitabine PrEP 1, 6
- The trials were stopped early by independent data safety monitoring boards due to clear evidence of superior protection against HIV acquisition 1, 6
- Provides an important alternative for individuals who struggle with daily oral medication adherence 6
Safety Profile
- Generally well-tolerated in clinical trials 2, 6
- Most common adverse effect: injection site reactions (up to 81% of participants), which typically diminish in severity over time 7, 5
- No clinically significant QT interval prolongation at therapeutic doses 3
- No dosage adjustment necessary for mild to moderate renal or hepatic impairment 3
Pre-Administration Requirements
- Comprehensive HIV testing is essential before initiating Apretude:
Practical Considerations
- Patients should have a 1-month supply of an appropriate tenofovir-based oral PrEP agent available for oral bridging in case of injection delays of 7 days or more 1, 7
- Apretude should not be used with potent inducers of UGT1A1 1
- Use with caution in individuals with gluteal implants or fillers 1
Transitioning Between PrEP Methods
- When transitioning from Apretude to oral PrEP (such as Descovy):
- Begin oral PrEP within 12 weeks after the last cabotegravir injection to maintain continuous HIV protection during the cabotegravir pharmacokinetic tail period 8
- Perform comprehensive HIV testing (antigen/antibody AND RNA testing) before initiating oral PrEP 8
- Schedule follow-up HIV testing 4-6 weeks after starting oral PrEP 8
Common Pitfalls to Avoid
- Inadequate HIV testing before initiation could miss early HIV infection 8, 7
- Delayed or missed injections without appropriate oral PrEP bridging may leave patients vulnerable to HIV acquisition 8
- Premature discontinuation without transition to another effective prevention method 8
Apretude represents a significant advancement in HIV prevention, particularly for individuals who have difficulty with daily oral medication adherence or prefer a less frequent dosing schedule.