Is cabotegravir (Apretude) injection every 2 months medically necessary for a patient with high risk heterosexual behavior, currently stable on Truvada (emtricitabine/tenofovir disoproxil fumarate), to switch to Apretude due to its greater efficacy in preventing HIV infection?

Medical Necessity Assessment: Cabotegravir (Apretude) for HIV Pre-Exposure Prophylaxis

Critical Issue: Wrong Medication Being Requested

This request should NOT be approved as submitted because the patient is being prescribed the WRONG medication for their indication. The patient is HIV-negative and requires PrEP (pre-exposure prophylaxis), but the insurance criteria being applied are for Cabenuva (cabotegravir + rilpivirine), which is exclusively for HIV treatment, not prevention 1, 2. The correct medication is Apretude (cabotegravir alone) for PrEP 2, 3.

Correct Medical Necessity Determination

Cabotegravir injectable (Apretude) for HIV PrEP IS medically necessary for this patient based on the following:

Patient Meets All Criteria for Injectable PrEP

• HIV-negative status confirmed: Patient has documented negative HIV-1 viral load tests (no HIV-1 RNA detected) for at least 6 months, most recently 8/22/24 1, 2
• High-risk behavior documented: Diagnosis Z72.51 (high-risk heterosexual behavior) with history of primary syphilis requiring treatment in 6/2024, indicating ongoing substantial HIV acquisition risk 1
• Currently on effective oral PrEP: Patient is stable on Truvada (tenofovir/emtricitabine), demonstrating commitment to HIV prevention 1
• Appropriate candidate for switch: Patient and provider have identified desire to switch to more efficacious option 3, 4

Superior Efficacy Justifies Switch

Injectable cabotegravir demonstrates significantly superior efficacy compared to oral tenofovir-based PrEP, with 78% reduction in HIV acquisition risk (HR = 0.22,95% CI: 0.08-0.59, p < 0.01) 4. This superior efficacy, combined with elimination of daily adherence requirements, provides strong clinical justification for switching from Truvada 3, 4.

Correct Dosing Schedule

The appropriate dosing regimen is 600 mg intramuscular gluteal injections with the first 2 injections separated by 4 weeks, then every 8 weeks (approximately every 2 months) thereafter 1, 5. The request for "every 2 months x 1 year" aligns with guideline recommendations, which would provide:

• Initial injection (loading dose)
• Second injection at 4 weeks
• Subsequent injections every 8 weeks for remainder of year (approximately 5 additional injections)
• Total: 7 injections over 12 months 1, 5

Required Monitoring and Safety Protocols

Pre-Injection Requirements (Each Visit)

• HIV testing mandatory before EVERY injection: Rapid point-of-care HIV test on day of injection, plus combined antibody/antigen test sent to laboratory (do not delay injection for lab results) 1, 5
• HIV RNA testing: Should be performed in addition to antibody/antigen testing to detect acute infection 1, 5

Ongoing Monitoring Schedule

• STI testing every 4 months (every second injection): Includes syphilis, chlamydia, gonorrhea testing given patient's history of syphilis 1
• Liver enzyme monitoring every 6 months: Particularly important given patient's documented history of transaminitis and hyperbilirubinemia 1, 2
• Renal function monitoring: Baseline and periodic assessment, though cabotegravir has better renal safety profile than tenofovir-based regimens 4

Injection Delay Protocol

• If injection delayed 7+ days but <8 weeks: Resume injections after negative HIV testing 1
• If injection delayed ≥8 weeks: Must "reload" with two injections 4 weeks apart before returning to every-8-week schedule 1, 5
• Oral bridging therapy: Patient should have 1-month supply of oral PrEP (tenofovir-based) available for delays ≥7 days 5

Critical Safety Considerations

Hepatotoxicity Monitoring

Given this patient's documented transaminitis history, enhanced hepatic monitoring is essential 2. The FDA label specifically warns about hepatotoxicity with cabotegravir and recommends monitoring liver chemistries 2. Baseline LFTs should be obtained and monitored every 6 months, with discontinuation if hepatotoxicity develops 1, 2.

Injection Site Reactions

Up to 81% of patients experience injection site reactions, though these typically diminish over time 5, 3. Manage aggressively with topical/systemic analgesics and hot/cold packs 1.

Resistance Risk if Seroconversion Occurs

If HIV acquisition occurs while on cabotegravir PrEP, immediate genotypic resistance testing including integrase resistance is mandatory, and treatment should begin with protease inhibitor or NNRTI-based regimen (NOT integrase inhibitor-based) 1, 5.

Common Pitfalls to Avoid

• Wrong medication/criteria applied: Do not use Cabenuva (treatment) criteria for Apretude (PrEP) indication 1, 2
• Inadequate HIV testing: Must perform comprehensive testing (antibody/antigen PLUS RNA) before each injection to avoid missing acute infection 1, 5
• Missing scheduled injections: Delays ≥8 weeks require reloading protocol; provide oral bridging supply 1, 5
• Insufficient hepatic monitoring: Patient's transaminitis history requires vigilant LFT monitoring 2
• Failure to test/treat STIs: Patient's syphilis history indicates high-risk behavior requiring regular STI screening 1

Cost-Effectiveness Consideration

Injectable cabotegravir for PrEP is cost-effective versus generic oral tenofovir/emtricitabine, with incremental cost-effectiveness ratio of $46,843 per QALY gained, well below standard willingness-to-pay thresholds 6. The superior efficacy prevents 4.5 additional HIV infections per 100 PrEP users compared to oral PrEP 6.

Recommendation Summary

APPROVE cabotegravir (Apretude) 600 mg IM injections for HIV PrEP with the following specifications:

• 7 total injections over 12 months: Initial dose, second dose at 4 weeks, then every 8 weeks x 5 doses 1, 5
• Mandatory HIV testing before each injection 1, 5
• LFT monitoring every 6 months given transaminitis history 1, 2
• STI screening every 4 months 1
• Oral PrEP bridging supply for potential delays 5