Can Cabenuva (cabotegravir and rilpivirine) and Apretude (cabotegravir) be combined in a person with known resistance to these medications?

Combining Cabenuva and Apretude in Patients with Known Resistance

Cabenuva (cabotegravir and rilpivirine) should not be used in individuals with documented or suspected resistance to either agent, making the combination with Apretude (cabotegravir) contraindicated in patients with known resistance to these medications. 1, 2

Understanding the Contraindication

• Long-acting cabotegravir plus long-acting rilpivirine (Cabenuva) is specifically not recommended in individuals with documented or suspected resistance to either cabotegravir or rilpivirine due to increased risk of treatment failure (evidence rating: AIIa) 1
• Using Cabenuva in patients with rilpivirine resistance would compromise one of the two active components, potentially leading to virologic failure and development of resistance to both drug classes 2
• Even in patients without pre-existing resistance, there is a 1-2% incidence of virologic failure with emergence of 2-class resistance with Cabenuva, which would be significantly higher in patients with known resistance 1, 2
• Apretude contains cabotegravir, the same active ingredient as one component of Cabenuva, so combining them would not address the resistance issue and could potentially worsen it 3, 4

Risks of Inappropriate Use

• Virologic failure with Cabenuva in resistant patients can lead to:
  • Development of additional resistance mutations 1, 2
  • Viral transmission if virologic rebound occurs 1
  • Future limitations of treatment options due to multi-class resistance 2, 5
• Clinical trials identified rilpivirine-associated resistance at baseline as a specific risk factor for virologic failure with Cabenuva 1, 6
• Resistance to cabotegravir (present in both Cabenuva and Apretude) would render both medications ineffective 3, 4

Alternative Treatment Options for Patients with Resistance

• For patients with documented resistance to cabotegravir or rilpivirine, regimens with a high barrier to resistance are recommended: 1, 2
  • Dolutegravir or bictegravir-based regimens with appropriate NRTIs
  • Boosted protease inhibitor-based regimens (particularly darunavir)
• For patients with extensive multiclass resistance (including to integrase inhibitors), agents with novel mechanisms of action should be considered: 1
  • Ibalizumab
  • Fostemsavir
  • Lenacapavir
• These novel agents should ideally be used in combination to allow for at least 2 fully active drugs (evidence rating: AIa) 1

Special Considerations

• For patients unable to take oral ART with advanced HIV disease, long-acting cabotegravir plus long-acting rilpivirine may only be considered under very specific circumstances: 1, 5
  • Unable to take oral ART consistently despite extensive efforts and clinical support
  • High risk of HIV disease progression (CD4+ cell count <200/μL or history of AIDS-defining complications)
  • Virus must be susceptible to both cabotegravir and rilpivirine
  • Intensive case management and adherence support must be provided
• Any patient with known resistance to either cabotegravir or rilpivirine would not meet these criteria 1, 2

Monitoring Recommendations

• For patients switching to alternative regimens due to resistance, viral load should be checked at 1 month and then every 3 months for a year to ensure ongoing viral suppression 1, 2
• 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
• Resistance testing is essential before selecting any new regimen for patients with known resistance 1