What is the best approach for managing the interaction between pantoprazole (proton pump inhibitor) and cabotegravir/rilpivirine (antiretroviral therapy) in a patient with HIV and gastroesophageal reflux disease?

Managing Pantoprazole-Rilpivirine Interaction in HIV Treatment

Direct Answer

Replace pantoprazole with famotidine 40mg once daily and take at the same time as oral cabotegravir and rilpivirine on an empty stomach (Option C). This approach addresses the critical drug interaction while maintaining GERD control and preserving the essential oral lead-in phase.

Rationale for This Recommendation

Why Pantoprazole Must Be Discontinued

• Concomitant use of pantoprazole with rilpivirine-containing products is contraindicated according to FDA labeling 1
• Proton pump inhibitors like pantoprazole decrease rilpivirine exposure by reducing gastric acidity, which impairs rilpivirine absorption and may reduce antiviral effect while promoting drug resistance 1
• This interaction persists regardless of dose timing or separation, making options B and D ineffective 1

Why the Oral Lead-In Cannot Be Skipped

• The oral lead-in phase (4-5 weeks) serves as a critical safety assessment period to identify tolerability issues before committing to long-acting injections 2
• This phase allows monitoring of GERD symptom control on famotidine and assessment of HIV viral load at 4-6 weeks to confirm virologic suppression 2
• Skipping the oral lead-in (Option A) eliminates this safety checkpoint and is not recommended by current guidelines 2

Why Famotidine Is the Appropriate Alternative

• H2-receptor antagonists like famotidine have significantly less impact on rilpivirine absorption compared to proton pump inhibitors 1
• Famotidine 40mg daily provides adequate GERD symptom control for most patients who previously required PPI therapy 3
• The oral lead-in allows assessment of whether famotidine adequately controls this patient's GERD symptoms before transitioning to long-acting injections 2

Why Calcium Antacids Are Inadequate

• Calcium antacids (Option D) provide only short-term symptom relief and are insufficient for managing chronic GERD, particularly in a patient with documented rebound effects when stopping pantoprazole 3
• This patient requires continuous acid suppression therapy, not episodic symptom management 3

Implementation Algorithm

Step 1: Transition Period (Week 0)

• Discontinue pantoprazole immediately 1
• Initiate famotidine 40mg once daily 2
• Begin oral cabotegravir 30mg and rilpivirine 25mg daily, taken with famotidine on an empty stomach 2

Step 2: Monitoring During Oral Lead-In (Weeks 1-4)

• Assess GERD symptom control on famotidine at each clinical contact 2
• Check HIV RNA at 4-6 weeks to confirm virologic suppression and ensure adequate rilpivirine levels 2
• Monitor for any tolerability issues with the oral cabotegravir/rilpivirine combination 2

Step 3: Transition to Injectable Therapy (Week 5+)

• If viral suppression is maintained and GERD symptoms are controlled, proceed to long-acting cabotegravir 400mg and rilpivirine 600mg intramuscular injections every 4-8 weeks 4
• Continue famotidine 40mg daily throughout injectable therapy 2

Step 4: Long-Term Monitoring

• Monitor HIV RNA every 3 months for the first year after switching 4
• Continue assessing GERD symptom control at each visit 2
• Monitor for injection site reactions, which occur in approximately 86-88% of patients but are typically mild to moderate with median duration of 3 days 5, 6

Critical Caveats and Pitfalls

Risk of Treatment Failure

• Long-acting cabotegravir plus rilpivirine carries a 1-2% risk of virologic failure with emergence of 2-class resistance even with adherence, a risk not observed with oral ART 4
• Risk factors include rilpivirine-associated resistance at baseline, viral subtype A6, and BMI > 30 4
• Clinicians must discuss the possibility of treatment failure and potential for viral transmission if virologic rebound occurs 4

Importance of Injection Adherence

• The long elimination half-lives (5.6-11.5 weeks for cabotegravir, 13-28 weeks for rilpivirine) mean that missed injections can result in prolonged subtherapeutic drug levels 7
• Patients unable to attend scheduled injections require close attention and interventions to return to care 4
• This regimen is more resource-intensive for clinicians and clinic staff than self-administered oral ART 4

Hepatitis B Considerations

• Long-acting cabotegravir plus rilpivirine does not provide treatment or protection against HBV infection 4
• Rescreening for HBV is warranted before switching, with immunization if indicated 4

Monitoring for Rebound GERD

• Given this patient's history of significant rebound effects when stopping pantoprazole, close monitoring during the famotidine transition is essential 3
• If GERD symptoms are inadequately controlled on famotidine during the oral lead-in, the switch to long-acting therapy should be reconsidered 2