What is the appropriate Highly Active Antiretroviral Therapy (HAART) regimen for a patient who has previously received cabotegravir (Integrase Inhibitor)?

HAART Regimen Selection for Patients Previously on Cabotegravir

For patients previously treated with cabotegravir, a boosted protease inhibitor-based regimen (darunavir/ritonavir) plus two NRTIs is the most appropriate HAART regimen due to the risk of integrase inhibitor resistance. 1

Assessment of Previous Cabotegravir Exposure

Before selecting a new HAART regimen, evaluate:

• Type of previous cabotegravir exposure (oral lead-in, long-acting injectable, PrEP)
• Duration of exposure
• Reason for discontinuation
• Viral load status at discontinuation
• Time since last cabotegravir dose

Critical Considerations

• Resistance testing: Obtain InSTI genotyping prior to initiating a new regimen 1
• Viral load: Determine current HIV RNA level
• CD4 count: Assess immune status

Recommended Regimen Selection Algorithm

First-line Recommendation:

• Darunavir (600mg) plus ritonavir (100mg) twice daily with TXF/XTC (tenofovir/emtricitabine or lamivudine) 1
  • High barrier to resistance
  • Effective against virus with potential InSTI resistance
  • Particularly important if patient received long-acting cabotegravir for PrEP

Alternative Options:

1. If InSTI resistance is definitively ruled out:

   • Bictegravir/TAF/FTC or Dolutegravir plus TXF/XTC 1
   • These second-generation InSTIs have higher barriers to resistance than cabotegravir

2. For patients with extensive multiclass resistance:

   • Consider novel mechanism agents (ibalizumab, fostemsavir, or lenacapavir) 1
   • Ideally combine to allow for 2 fully active drugs

Monitoring Recommendations

• More frequent viral load monitoring in first year after switch (every 1-3 months) 1
• Assess adherence at each visit
• Monitor for drug-specific adverse effects

Important Caveats

• Avoid first-generation InSTIs: Raltegravir and elvitegravir are not recommended due to lower resistance barriers 1
• Avoid NNRTIs: Including rilpivirine, as cross-resistance may exist if the patient received cabotegravir/rilpivirine 1
• Caution with two-drug regimens: Not recommended with suspected resistance 1
• Pregnancy considerations: If patient is pregnant, darunavir/ritonavir plus TXF/XTC is preferred 1

Special Scenarios

For Patients with Virologic Failure on Cabotegravir

• Collect resistance testing before switching therapy
• Implement boosted protease inhibitor regimen while awaiting results 1

For Patients Who Used Cabotegravir for PrEP

• Avoid InSTI-based regimens until resistance testing confirms susceptibility 1
• Ritonavir-boosted darunavir plus TXF/XTC is recommended 1

Recent real-world data from the OPERA cohort shows that patients with adherence challenges may benefit from injectable regimens with high genetic barriers to resistance 2. For patients with extensive resistance patterns, emerging evidence suggests that combination long-acting therapies like lenacapavir/cabotegravir may be effective, with 94% of patients achieving viral suppression in a recent case series 3.