Long-Acting Injectable Cabotegravir for HIV Prevention
Long-acting injectable cabotegravir (CAB-LA) is the most effective injectable PrEP option currently available, demonstrating superior efficacy compared to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in preventing HIV acquisition in high-risk populations. 1
Efficacy Data on Injectable Cabotegravir PrEP
- CAB-LA demonstrated superior efficacy to daily oral TDF/FTC in large randomized clinical trials, showing a 66% reduction in HIV incidence (hazard ratio 0.34) in cisgender men who have sex with men and transgender women 1
- The injectable regimen is administered at a dose of 600 mg (3 mL) by gluteal intramuscular injection, with the first two injections separated by 4 weeks and subsequent injections every 8 weeks 2
- CAB-LA has received regulatory approval for prevention of sexual acquisition of HIV across populations based on strong clinical trial evidence (evidence rating: AIa) 2
Administration Protocol
- An oral cabotegravir lead-in period of 4-5 weeks is optional but recommended for those with severe atopic histories or those who request it (evidence rating: BIII) 2
- For maximum protection after the first injection, an oral PrEP regimen should overlap with the first injection by 7 days (evidence rating: BIII) 2
- Persons receiving CAB-LA should have a 1-month supply of appropriate tenofovir-based oral PrEP on hand in case of injection delays of 7 days or more (evidence rating: BIII) 2
Safety Profile
- CAB-LA is generally well tolerated, with injection site reactions being the most common adverse event, reported in 81.4% of participants in clinical trials 1
- Unlike oral TDF-based PrEP, CAB-LA does not have renal toxicity concerns and can be used in patients with creatinine clearance as low as 30 mL/min 3
- No dosage adjustment is necessary for patients with mild to moderate renal impairment (creatinine clearance 30-90 mL/min) or severe renal impairment (creatinine clearance 15-30 mL/min) 3
Special Considerations and Limitations
- CAB-LA is not recommended for postexposure prophylaxis (PEP) due to lack of data on safety, tolerability, and efficacy in this setting 2
- A recent animal study indicated that PEP with long-acting cabotegravir was only partially effective and demonstrated late breakthrough infections 2
- Resistance concerns exist: in breakthrough infections, INSTI resistance-associated substitutions were detected in some cases, including R263K, E138A+Q148R, E138K+Q148K, and G140A+Q148R mutations 3
Cost-Effectiveness
- Despite higher upfront costs compared to generic oral FTC/TDF, CAB-LA has been found to be cost-effective with an incremental cost-effectiveness ratio of $46,843 per QALY gained 4
- CAB-LA prevented 4.5 more primary and secondary HIV infections per 100 PrEP users compared to oral PrEP in cost-effectiveness modeling 4
Future Developments
- A newer injectable PrEP agent, lenacapavir (LEN), was approved in June 2025 with a more favorable dosing schedule of every 6 months (compared to every 2 months for CAB-LA) 5
- Lenacapavir demonstrated 96-100% efficacy in clinical trials with a favorable safety profile, primarily showing mild to moderate injection site reactions 5
Clinical Recommendations
- CAB-LA is recommended for people likely to be exposed to HIV sexually (evidence rating: AIa) 2
- While specific data for injection drug exposures are limited, CAB-LA is recommended for people who inject drugs who are also at risk for acquiring HIV through sexual exposures (evidence rating: AIII) 2
- Regular HIV testing is essential before each injection to prevent development of resistance, as delayed detection of HIV infection has been noted in some cases 1
CAB-LA represents a significant advancement in HIV prevention, offering an alternative to daily oral PrEP that may improve adherence and effectiveness in populations at high risk for HIV acquisition.