What is the best approach to bridge a patient with a planned missed injection of Cabenuva (cabotegravir and rilpivirine) with Biktarvy (bictegravir, emtricitabine, and tenofovir alafenamide)?

Bridging Cabenuva with Biktarvy for Planned Missed Injections

Direct Answer

Yes, you can bridge a patient with Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) during a planned missed Cabenuva injection, and this represents a highly effective strategy given Biktarvy's high barrier to resistance and proven efficacy even in patients with archived NRTI resistance. 1

Clinical Approach Algorithm

Step 1: Timing of Oral Bridge Initiation

• 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). 1
• Do not wait beyond the scheduled injection date, as cabotegravir and rilpivirine levels decline over time, creating risk for subtherapeutic drug levels and potential resistance development. 1

Step 2: Duration of Oral Bridge

• 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. 1
• This overlap ensures adequate drug levels are maintained during the transition back to long-acting therapy. 1

Step 3: Resuming Cabenuva

• When resuming Cabenuva after the planned interruption, restart with the standard maintenance dose (cabotegravir 400mg/rilpivirine 600mg monthly or 600mg/900mg every 8 weeks) without requiring a new oral lead-in or loading doses. 2
• Administer the injection on the originally scheduled date or as soon as feasible after the planned interruption ends. 2

Why Biktarvy is an Excellent Bridge Option

High Barrier to Resistance

• Bictegravir combined with two NRTIs maintains efficacy even in patients with archived M184V/I mutations, making it robust for bridging scenarios where resistance concerns may exist. 1
• The integrase inhibitor bictegravir has a high genetic barrier to resistance development, with no treatment-emergent resistance observed in clinical trials through 5 years of follow-up. 3, 4, 5

Compatibility with Cabenuva Components

• Both Cabenuva and Biktarvy contain integrase inhibitors (cabotegravir and bictegravir, respectively), providing class continuity that minimizes risk of resistance development during the bridge period. 1, 3
• Biktarvy's NRTI backbone (emtricitabine/tenofovir alafenamide) provides additional coverage that Cabenuva lacks, offering robust viral suppression. 3, 4

Proven Efficacy in Treatment-Experienced Patients

• Biktarvy demonstrated non-inferiority to protease inhibitor-based regimens in treatment-experienced patients with viral suppression, with only 0.7% experiencing virologic failure at 48 weeks. 6
• In switching studies, 88-90% of patients maintained HIV-1 RNA <50 copies/mL at 96 weeks when switched to Biktarvy. 4, 5

Critical Monitoring During Bridge Period

Viral Load Assessment

• Check HIV RNA at 4-6 weeks after starting Biktarvy bridge to confirm maintained viral suppression during the oral therapy period. 2
• Recheck viral load 4-6 weeks after resuming Cabenuva injections to ensure successful transition back to long-acting therapy. 1, 2

Adherence Counseling

• Emphasize the critical importance of daily Biktarvy adherence during the bridge period, as missed oral doses create greater risk for resistance than the long-acting formulation. 1
• Patients who struggle with daily oral adherence may not be good candidates for planned interruptions of Cabenuva. 1

Important Caveats and Pitfalls

Resistance Screening Before Cabenuva Resumption

• 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. 1, 7
• Documented or suspected resistance to either cabotegravir or rilpivirine is a contraindication to resuming Cabenuva. 1, 7

Hepatitis B Considerations

• Biktarvy contains tenofovir alafenamide and emtricitabine, both active against HBV, making it particularly suitable for patients with HBV co-infection during the bridge period. 3
• When resuming Cabenuva (which lacks HBV activity), ensure HBV treatment is continued separately if the patient has chronic HBV infection. 1

Risk of Two-Class Resistance with Cabenuva

• Cabenuva carries a 1-2% risk of virologic failure with emergence of both integrase inhibitor and NNRTI resistance even with perfect adherence, a risk not seen with oral regimens like Biktarvy. 1, 2
• This risk is higher with the every-8-week dosing schedule (75% developed rilpivirine resistance and 60% developed integrase resistance among those with virologic failure). 1
• Discuss with patients whether resuming Cabenuva after a planned interruption is worth this inherent risk, particularly if multiple interruptions are anticipated. 1, 2

Alternative to Consider

• If multiple planned interruptions are expected, consider permanently switching to Biktarvy rather than repeatedly bridging, as Biktarvy has demonstrated durable viral suppression through 5 years with no treatment-emergent resistance. 5
• Biktarvy offers the advantage of patient-controlled dosing flexibility without the resource-intensive clinic visits required for Cabenuva administration. 1, 8