What is a suitable HIV treatment regimen for a patient with resistance to rilpivirine (Edurant) and tenofovir (Viread), who prefers non-oral medications?

Treatment Regimen for HIV Patient with Resistance to Rilpivirine and Tenofovir Who Prefers Non-Oral Medications

For an HIV patient with resistance to rilpivirine and tenofovir who prefers non-oral medications, lenacapavir injection every 6 months is the most appropriate treatment option, not the combination of cabotegravir and rilpivirine injections, due to documented rilpivirine resistance.

Understanding the Patient's Situation

• The patient has documented resistance to rilpivirine and tenofovir, indicating multiclass drug resistance 1
• The patient prefers non-oral HIV medications, suggesting potential adherence challenges with daily oral regimens 1
• The HIV specialist has ordered cabotegravir injection every two months and lenacapavir injection every 6 months

Why Cabotegravir/Rilpivirine (Cabenuva) is Contraindicated

• Patients with documented resistance to rilpivirine should not receive Cabenuva (cabotegravir/rilpivirine) due to increased risk of treatment failure 2
• Using Cabenuva in patients with rilpivirine resistance would significantly increase the risk of virologic failure and development of resistance to both drug classes 2
• The FDA label for cabotegravir specifically indicates it should be used in patients "with no known or suspected resistance to either cabotegravir or rilpivirine" 3
• Rilpivirine resistance compromises one of the two active components of Cabenuva, potentially leading to virologic failure 2, 4

Appropriate Injectable Treatment Options

• Lenacapavir (administered every 6 months) is recommended for patients with multiclass drug resistance, including resistance to NNRTIs like rilpivirine 1
• For patients with extensive multiclass resistance, agents with novel mechanisms of action such as lenacapavir are recommended, ideally in combination to allow for 2 fully active drugs (evidence rating: AIa) 1
• Lenacapavir has a novel mechanism of action that remains effective against virus resistant to other antiretroviral classes 1, 5

Treatment Algorithm for This Patient

1. First step: Confirm resistance patterns through comprehensive resistance testing while the patient is on the current failing regimen 1

2. Treatment selection:

   • Use lenacapavir (every 6 months) as the backbone of the injectable regimen 1, 5
   • Consider adding another fully active agent with a different mechanism of action 1
   • Continue treatment with NRTIs that retain partial activity even in the presence of resistance mutations (evidence rating: AIIa) 1

3. Monitoring:

   • Check viral load one month after switching regimens 1
   • Continue monitoring viral load every 3 months for the first year 2
   • Monitor for potential adverse effects of the new regimen 1

Important Considerations and Caveats

• The E138K mutation is commonly associated with rilpivirine resistance and often confers cross-resistance to other NNRTIs, further limiting treatment options 4, 6
• Virologic failure with inappropriate use of Cabenuva can lead to development of resistance to both integrase inhibitors and NNRTIs, further limiting future treatment options 2, 7
• Injectable antiretrovirals have expanded treatment options for individuals with difficulty adhering to daily oral medications or those with multidrug-resistant HIV 5
• For patients with poor adherence to oral medications, intensive case management and adherence support should accompany injectable regimens 1