What is the protocol for administering Cabenuva (cabotegravir + rilpivirine) injections that are two weeks overdue?

Protocol for Administering Cabenuva Injections That Are 2 Weeks Overdue

For Cabenuva injections that are 2 weeks overdue, simply administer the delayed injection as soon as possible and continue with the regular dosing schedule thereafter—no reloading protocol is required at this delay interval. 1

Understanding the Delay Threshold

The critical distinction in managing delayed Cabenuva injections centers on whether the delay exceeds 8 weeks from the previous injection:

• For the second injection (normally due at week 4): Reloading is only required if ≥12 weeks have elapsed since the first injection 1
• For all subsequent injections (normally due every 8 weeks): Reloading is only required if ≥16 weeks have elapsed since the prior injection 1

A 2-week delay does not approach these thresholds, meaning your patient remains well within the therapeutic window for standard continuation dosing. 1

Immediate Management Steps

1. Administer the Overdue Injection Promptly

• Give the scheduled dose (cabotegravir 400 mg + rilpivirine 600 mg for monthly dosing, or cabotegravir 600 mg + rilpivirine 900 mg for every-2-month dosing) via gluteal intramuscular injection as soon as the patient presents 2
• Use the standard 3 mL volume administered into the gluteal muscle only—never use anterior thigh injection sites due to inadequate pharmacokinetics 1

2. Oral Bridging Considerations

Patients should have been using oral PrEP bridging if the delay was ≥7 days, as recommended by the International Antiviral Society-USA guidelines 1. If they did not:

• Assess HIV exposure risk during the delay period 1
• If significant exposure occurred within the past 72 hours, consider post-exposure prophylaxis (PEP) with a 3-drug regimen for 28 days before resuming Cabenuva 1
• Perform HIV testing before administering the delayed injection to rule out acute infection 3, 2

3. Resume Regular Dosing Schedule

• For monthly dosing: Schedule the next injection 4 weeks from the delayed injection you just administered 2
• For every-2-month dosing: Schedule the next injection 8 weeks from the delayed injection you just administered 2
• The dosing schedule essentially "resets" from the date of the delayed injection 4

HIV Testing Requirements

Mandatory HIV testing must be performed before every Cabenuva injection, including this delayed dose 3, 2:

• Use a fourth- or fifth-generation laboratory-based antigen-antibody assay 1, 3
• Ideally include HIV RNA testing with a lower limit of quantification ≤50 copies/mL 1, 3
• If HIV RNA testing is unavailable, proceed with rapid point-of-care antibody testing while awaiting laboratory confirmation 1, 3

When Reloading IS Required (Not Applicable Here)

For context, the reloading protocol applies only when delays are substantially longer 1:

• If the second injection is ≥8 weeks late (≥12 weeks total from first injection): Give two injections 4 weeks apart before returning to every-8-week dosing 1
• If any subsequent injection is ≥8 weeks late (≥16 weeks total from prior injection): Give two injections 4 weeks apart before returning to every-8-week dosing 1

This expert consensus guidance differs from the FDA package insert and represents the most current International Antiviral Society-USA recommendations. 1

Preventing Future Delays

Patient Education

• Provide patients with a 1-month supply of tenofovir-based oral PrEP for bridging if injections are delayed ≥7 days 1
• Emphasize the importance of maintaining injection visit adherence, which exceeds 89% in real-world cohorts 5

Injection Scheduling Flexibility

• Monthly dosing allows a ±7-day window before oral bridging becomes necessary 1
• Every-2-month dosing provides greater scheduling flexibility but requires the same vigilance for delays ≥7 days 1

Common Pitfalls to Avoid

• Do not unnecessarily restart the reloading protocol for delays <8 weeks—this wastes medication and creates unnecessary injection burden 1
• Do not skip HIV testing even for "minor" delays, as this is a mandatory safety requirement before every injection 3, 2
• Do not use anterior thigh injection sites as an alternative—these fail to achieve adequate drug levels and have poor tolerability 1
• Do not forget to assess for drug interactions with UGT1A1 inducers (rifampin, carbamazepine, phenytoin, phenobarbital) which are contraindicated with cabotegravir 3, 2

Monitoring After the Delayed Injection

• Assess for injection site reactions, which occur commonly but are typically mild-to-moderate (grade 1-2 in 99% of cases) with median duration of 3 days 6
• Monitor for depressive symptoms, as depressive disorders have been reported with Cabenuva 2
• Continue routine virologic monitoring every 24 weeks, with virologic suppression rates remaining >96% in real-world cohorts 7, 5, 8