Is Cabotegravir (Cabotegravir) 1 mg injection medically necessary for a patient with suspected exposure to HIV and intolerance to oral Pre-Exposure Prophylaxis (PrEP), affecting adherence and increasing the risk of HIV infection?

Medical Necessity of Cabotegravir Injection for HIV PrEP in Patient with Oral PrEP Intolerance

Cabotegravir injection (J0739) is medically necessary for this patient with documented intolerance to oral PrEP affecting adherence, as long-acting injectable cabotegravir is FDA-approved specifically for this indication and demonstrates superior efficacy to oral PrEP in preventing HIV acquisition. 1

Regulatory Approval and Indication

• Cabotegravir extended-release injectable suspension received FDA approval for HIV pre-exposure prophylaxis in at-risk adults and adolescents weighing ≥35 kg who have a negative HIV-1 test prior to initiation 1
• The International Antiviral Society-USA Panel (2020) provides evidence rating AIb for intramuscular gluteal injections with 600 mg of cabotegravir every 8 weeks after an initial 4-week interval between the first 2 injections 2
• Long-acting cabotegravir received regulatory approval based on large randomized clinical trials demonstrating superior efficacy compared to oral TDF-FTC 3

Clinical Justification for This Patient

This patient meets the specific criteria for cabotegravir injection:

• Documented intolerance to oral PrEP: The patient reports intolerable side effects to oral PrEP that have affected adherence, which is the precise clinical scenario where injectable cabotegravir provides critical benefit 1
• High-risk status: The patient has suspected HIV exposure (Z20.6) and is currently attempting PrEP, indicating ongoing high-risk behavior 1
• Adherence concerns: Poor adherence to oral PrEP places the patient at substantially increased risk of HIV acquisition, and the FDA label specifically addresses this by noting that missing doses increases HIV infection risk 1

Efficacy Evidence Supporting Medical Necessity

• Meta-analysis demonstrates that long-acting cabotegravir is associated with significantly lower risk of HIV infection compared to oral TDF-FTC (HR = 0.22,95% CI: 0.08-0.59, p < 0.01) 4
• Clinical trials showed superior efficacy in preventing HIV-1 acquisition in at-risk transgender women, cisgender men who have sex with men, and cisgender women 5
• The every-8-week dosing schedule addresses the adherence barrier that has compromised this patient's protection with daily oral therapy 3

Required Pre-Initiation Testing and Monitoring

Before initiating cabotegravir, the following must be documented:

• HIV-1 negative status confirmed by combined antibody/antigen test (fourth generation) AND HIV RNA test 2, 1
• The patient's current HIV 1/2 AG AND AB, fourth generation screen showing non-reactive status satisfies this requirement 1
• Assessment for acute HIV symptoms (fever, fatigue, joint/muscle aches, sore throat, rash, enlarged lymph nodes) within the past month, as these could indicate recent HIV infection that standard testing might miss 1

Common pitfall to avoid: Inadequate HIV testing before initiation could miss early HIV infection, which would lead to functional monotherapy and development of integrase resistance 3

Dosing Protocol

• Initial injection followed by second injection 4 weeks later, then every 8 weeks thereafter 2, 3
• Rapid point-of-care HIV testing should be performed on the day of each injection prior to administration 2
• If an injection is 8 or more weeks late, restart with two injections separated by 4 weeks before returning to the 8-week interval 2, 3

Safety Profile and Tolerability

• The most common adverse event is injection site reactions, occurring in up to 81% of participants but typically diminishing in severity over time 3
• Injection site pain was the most frequently reported Grade ≥2 adverse event, but only 4% of participants withdrew due to injection intolerance in clinical trials 6
• Cabotegravir demonstrates less decreased creatinine clearance compared to oral TDF-FTC (RR = 0.96,95% CI: 0.93-0.99, p < 0.01), which is an additional safety advantage 4
• Liver enzyme tests should be administered every 6 months 2

Ongoing Monitoring Requirements

• HIV testing at each injection visit (every 8 weeks) 2
• Sexually transmitted infection testing every 4 months (every second injection) 2
• The patient must maintain HIV-negative status to continue cabotegravir for PrEP 1

Critical Safety Considerations

If HIV infection occurs while on cabotegravir:

• Cabotegravir alone is not a complete treatment for HIV-1 1
• Transition to a dolutegravir-, bictegravir-, or ritonavir-boosted darunavir-based regimen is recommended initially, with subsequent tailoring based on resistance testing 2
• Genotypic testing including for integrase resistance must be obtained 2

Resistance concerns: Five participants in HPTN 083 who acquired HIV while on cabotegravir with adequate drug levels developed integrase resistance-associated substitutions, including mutations conferring 6- to 13-fold reduced susceptibility to cabotegravir 1

Adherence Support and Patient Education

• The patient must understand that cabotegravir does not prevent other sexually transmitted infections and should use barrier protection 1
• A 1-month supply of oral tenofovir-based PrEP should be available for bridging if injection delays occur of 7 days or more 3
• If discontinuing injectable PrEP while still at risk, transition to another recommended PrEP regimen is essential 2

Conclusion on Medical Necessity

This case represents a textbook indication for cabotegravir injection: documented oral PrEP intolerance affecting adherence in a high-risk patient with confirmed HIV-negative status. The superior efficacy, improved adherence profile, and FDA approval for precisely this clinical scenario establish clear medical necessity. 2, 3, 1, 5, 4