Can a patient with HIV who is resistant to rilpivirine (Edurant) take Cabenuva (cabotegravir/rilpivirine)?

Cabenuva is Not Recommended for Patients with Rilpivirine Resistance

Patients with documented or suspected resistance to rilpivirine should not receive Cabenuva (cabotegravir/rilpivirine) due to increased risk of treatment failure. 1

Rationale for Contraindication

• Long-acting cabotegravir plus long-acting rilpivirine is specifically not recommended in individuals with documented or suspected resistance to either agent (evidence rating: AIIa) 1
• Rilpivirine resistance would compromise one of the two active components of Cabenuva, potentially leading to virologic failure and development of resistance to both drug classes 1
• Clinical trials identified rilpivirine-associated resistance at baseline (detected by proviral DNA genotyping) as a risk factor for virologic failure with Cabenuva 1

Clinical Implications of Using Cabenuva in Rilpivirine-Resistant Patients

• An important limitation of injectable cabotegravir and rilpivirine is a 1-2% incidence of virologic failure with emergence of 2-class resistance even with adherence to scheduled injections in patients without pre-existing resistance 1
• Using Cabenuva in patients with rilpivirine resistance would significantly increase this risk 1
• Virologic failure with Cabenuva can lead to:
  • Viral transmission if virologic rebound occurs 1
  • Future limitations of treatment options due to development of resistance to both integrase inhibitors and NNRTIs 1

Alternative Treatment Options for Rilpivirine-Resistant Patients

• For patients with rilpivirine resistance, regimens with a high barrier to resistance are recommended, such as: 1
  • Dolutegravir or bictegravir-based regimens with appropriate NRTIs 1
  • Boosted darunavir-based regimens 1
• For patients with extensive multiclass resistance (including InSTIs), agents with novel mechanisms of action should be considered: 1
  • Ibalizumab 1
  • Fostemsavir 1
  • Lenacapavir 1, 2
• These agents should ideally be used in combination to allow for 2 fully active drugs 1

Special Considerations for Treatment Selection

• A thorough review of the patient's ART history, prior resistance testing, and comorbidities is mandatory before making any treatment changes 3, 4
• For patients who prefer injectable treatment but have rilpivirine resistance, alternative long-acting options may be available in the future, but currently oral therapy with a high barrier to resistance is recommended 1, 2
• Continued treatment with NRTIs such as tenofovir/emtricitabine is recommended even in the presence of extensive resistance mutations, as they retain partial activity 1

Monitoring Recommendations

• For patients switching to alternative regimens due to rilpivirine resistance, viral load should be checked at 1 month and then every 3 months for a year to ensure ongoing viral suppression 1
• Patients with NRTI resistance who switch to dual NRTI plus dolutegravir or bictegravir regimens should be monitored more closely in the first year after the switch 1
• Adherence support should be provided for patients who were interested in Cabenuva due to difficulty with daily oral medication adherence 3

Cabenuva represents an important treatment option for many patients with HIV, but its use must be limited to those without resistance to either of its component drugs to maximize efficacy and prevent the development of further resistance.