Is Cabenuva (cabotegravir/rilpivirine) 600/900mg intramuscularly (IM) every 8 weeks medically indicated for a patient with Human Immunodeficiency Virus (HIV) and a history of Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) and Juluca (dolutegravir/rilpivirine) to maintain a suppressed, undetectable viral load?

Is Cabenuva 600/900mg IM Every 8 Weeks Medically Indicated for This Patient?

Yes, Cabenuva (cabotegravir/rilpivirine) 600/900mg IM every 8 weeks is medically indicated for this 49-year-old female patient with HIV who is virologically suppressed and has a history of successful treatment with Biktarvy and Juluca, provided she has no prior virological failure, no archived resistance to cabotegravir or rilpivirine, and no hepatitis B co-infection. 1, 2

Key Eligibility Criteria Met

This patient meets the essential criteria for Cabenuva therapy based on current guidelines:

• Virological suppression status: The patient must have maintained HIV-1 RNA <50 copies/mL for at least 6 months on her current regimen without any history of virological failure 1
• No archived resistance: She must have no known or suspected resistance to either cabotegravir (integrase inhibitor) or rilpivirine (NNRTI) based on historical genotypic testing 1, 2
• No hepatitis B co-infection: Cabenuva does not provide treatment or protection against HBV, making it contraindicated in co-infected patients 3
• Prior successful ART history: Her history of Biktarvy (integrase inhibitor-based) and Juluca (dolutegravir/rilpivirine dual therapy) demonstrates tolerance to both integrase inhibitors and rilpivirine 1

Evidence Supporting Every 8-Week Dosing

The International Antiviral Society-USA panel specifically recommends cabotegravir 600mg plus rilpivirine 900mg every 8 weeks as an appropriate maintenance therapy option (evidence rating: BIb). 1

The ATLAS-2M trial demonstrated non-inferiority of every 8-week dosing compared to every 4-week dosing at 48 weeks, with similar efficacy (HIV-1 RNA ≥50 copies/mL: 2% vs 1%) and safety profiles 4. The SOLAR study further confirmed that long-acting cabotegravir plus rilpivirine every 2 months maintained virological suppression comparable to daily oral bictegravir/emtricitabine/tenofovir alafenamide 5.

Critical Caveat: Resistance Risk with 8-Week Dosing

A significant concern exists with the every 8-week regimen: among the 1.5% who experienced confirmed virological failure in ATLAS-2M, 75% (6 of 8) developed rilpivirine resistance and 60% developed integrase inhibitor resistance. 1

Risk factors for virological failure include:

• Archived rilpivirine-associated resistance mutations at baseline 3, 4
• HIV-1 subtype A6 3
• BMI >30 kg/m² 3
• Poor adherence to injection schedule 1

Implementation Algorithm

Pre-Switch Requirements:

1. Confirm current virological suppression: HIV-1 RNA must be <50 copies/mL (ideally undetectable) 2
2. Obtain resistance testing: Review all historical genotypic resistance tests to exclude archived NNRTI or integrase resistance mutations 1, 2, 6
3. Screen for hepatitis B: Perform HBsAg, anti-HBc, and anti-HBs testing; if positive, Cabenuva is contraindicated 3
4. Assess adherence capacity: Patient must be able to attend scheduled injections every 8 weeks; those with poor adherence to care are not good candidates 1

Initiation Strategy:

Optional oral lead-in phase (evidence rating: BIb): 1, 3

• Cabotegravir 30mg + rilpivirine 25mg orally daily for 4-5 weeks
• This allows assessment of tolerability before committing to long-acting injections
• Check HIV-1 RNA at 4-6 weeks to confirm continued suppression 3

Direct injection initiation (if oral lead-in declined):

• First two injections: cabotegravir 600mg + rilpivirine 900mg IM separated by 4 weeks
• Subsequent injections: every 8 weeks thereafter 1, 4

Mandatory Monitoring Schedule:

HIV-1 RNA testing: 2, 3

• Every 3 months for the first year after switching
• If stable, can extend to every 4-6 months thereafter
• Perform testing prior to each injection visit

Additional monitoring: 2

• Liver enzyme tests every 6 months
• STI screening every 4 months (every second injection)
• If virological failure occurs (confirmed HIV-1 RNA ≥200 copies/mL on two sequential tests), perform genotypic resistance testing including integrase resistance mutations 2

Managing Missed Injections

If an injection is missed by more than 7 days: 2

• Oral bridging therapy with cabotegravir 30mg + rilpivirine 25mg daily is required
• Resume injections as soon as feasible
• This prevents subtherapeutic drug levels that could lead to resistance development

Advantages Over Her Previous Regimens

Switching from daily oral therapy (Biktarvy or Juluca) to Cabenuva offers:

• Reduced pill burden: From daily oral tablets to 6 injections per year 1, 7
• Improved adherence: Eliminates daily dosing requirements and associated stigma 7, 5
• Potential metabolic benefits: Reduction in NRTI-related bone, kidney, and cardiovascular complications 1
• Patient preference: Most participants in clinical trials preferred long-acting injectable over previous oral regimens 1

Absolute Contraindications

Do not prescribe Cabenuva if: 6

• Documented resistance to rilpivirine or cabotegravir exists
• Hepatitis B co-infection is present
• Patient has history of virological failure on any ART regimen
• Patient cannot reliably attend scheduled injection appointments
• Patient is pregnant or planning pregnancy (requires transition to alternative regimen) 2

Quality of Life and Morbidity Considerations

This regimen prioritizes quality of life through: 5

• Addressing psychosocial issues associated with daily oral treatment
• Reducing HIV-related stigma from daily pill-taking
• Maintaining durable virological suppression (95% suppression rates in clinical trials) 1
• Low discontinuation rates due to adverse events (excluding injection site reactions) 4, 5

Injection site reactions are common (70-92% of participants) but rarely lead to discontinuation: 1, 4, 5

• Most are Grade 1-2 (mild to moderate)
• Median duration is 3 days
• Frequency decreases over time
• Only 1-6% discontinue due to adverse events 5, 8