What is the protocol for a patient with HIV (Human Immunodeficiency Virus) infection who has missed a dose of Cabenuva (cabotegravir and rilpivirine)?

Cabenuva Unplanned Missed Dose Protocol

Immediate Action Based on Dosing Schedule

For unplanned missed Cabenuva injections, initiate oral bridging therapy with cabotegravir 30mg plus rilpivirine 25mg daily (taken together with food) starting at the time the next injection would have been due, continuing until the day injection dosing is restarted. 1

For Monthly (Q4W) Dosing Schedule

• If the patient misses a monthly injection by more than 7 days, start oral therapy with VOCABRIA (cabotegravir) 30mg plus EDURANT (rilpivirine) 25mg daily 1
• The first oral dose should be taken 1 month (±7 days) after the last injection dose 1
• Continue daily oral therapy until the day injection dosing is restarted 1
• For oral therapy durations greater than 2 months, switch to an alternative oral antiretroviral regimen rather than continuing cabotegravir/rilpivirine orally 1

For Every-2-Month (Q8W) Dosing Schedule

• If the patient misses an every-2-month injection by more than 7 days, start oral therapy with cabotegravir 30mg plus rilpivirine 25mg daily 1
• The first oral dose should be taken approximately 2 months after the last injection dose 1
• Continue daily oral therapy until the day injection dosing is restarted 1
• For oral therapy durations greater than 2 months, switch to an alternative oral antiretroviral regimen 1

Alternative Bridging Strategy: Biktarvy

For patients with concerns about adherence to twice-daily oral dosing or those requiring extended bridging periods, Biktarvy represents a superior alternative to oral cabotegravir/rilpivirine due to its high barrier to resistance and once-daily dosing. 2

• Start Biktarvy at the time the next Cabenuva injection would have been due (either at the 4-week or 8-week mark, depending on the patient's dosing schedule) 2
• Continue Biktarvy for the entire duration of the missed injection period plus at least 1-2 weeks beyond when the patient returns for their next scheduled Cabenuva injection 2
• Bictegravir maintains efficacy even in patients with archived M184V/I mutations, making it robust for bridging scenarios 2
• The integrase inhibitor bictegravir has a high genetic barrier to resistance development, minimizing risk during the bridge period 2

Critical Monitoring During Bridge Period

• Emphasize the critical importance of daily adherence during the bridge period, as missed oral doses create greater risk for resistance than the long-acting formulation 2
• Check HIV RNA at 4-6 weeks after resuming Cabenuva injections to ensure successful transition back to long-acting therapy 2
• If the bridge period extends beyond 2-3 months or if there are adherence concerns, consider resistance testing before resuming Cabenuva to ensure no emergent resistance to rilpivirine or integrase inhibitors has developed 2

Resuming Injection Dosing

• Resume Cabenuva injections on the day oral dosing completes or within 3 days 1
• For monthly dosing: restart with the standard monthly continuation dose 1
• For every-2-month dosing: restart with the standard every-2-month continuation dose 1
• Monitor viral load at 4-6 weeks after resuming injections to confirm maintained suppression 2

Key Caveats and Pitfalls

• Cabenuva carries a 1-2% risk of virologic failure with emergence of both integrase inhibitor and NNRTI resistance even with perfect adherence to scheduled injections 3, 2, 4
• Poor adherence to injection schedules is a risk factor for virologic failure 3, 2
• Patients unable to attend scheduled injections require close attention and interventions to return to care 3, 2
• The long-acting nature of Cabenuva means that delayed or missed injections result in prolonged periods with subtherapeutic drug levels, increasing resistance risk 3
• Real-world data shows that 90% of continuation injections are administered on time (within ±7 days), with high virologic control maintained when adherence is good 5

When to Consider Alternative Regimens

• If oral bridging therapy is needed for more than 2 months, transition to a different oral antiretroviral regimen rather than continuing oral cabotegravir/rilpivirine 1
• If the patient demonstrates recurrent inability to attend scheduled injections, consider switching to a daily oral regimen with a high barrier to resistance (such as bictegravir or dolutegravir-based regimens) 3, 4
• If resistance testing reveals emergent rilpivirine or integrase inhibitor resistance during the bridge period, do not resume Cabenuva 4, 6