What is the best antiretroviral regimen change to minimize interactions with comedications in a patient with HIV and multiple comorbidities?

Optimal Antiretroviral Regimen Change to Minimize Drug Interactions

The best regimen change is bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) combined with darunavir/cobicistat (Option A), as this maintains the necessary high barrier to resistance for multi-drug resistant virus while eliminating cobicistat-mediated interactions with fluticasone that caused the patient's recent adrenal suppression. 1

Critical Problem Identification

The patient's recent hospitalization for corticosteroid-induced adrenal suppression was caused by a drug-drug interaction between cobicistat (in his current elvitegravir/cobicistat/FTC/TAF) and fluticasone furoate/vilanterol for COPD. 2

• Cobicistat is a potent CYP3A4 inhibitor that dramatically increases systemic corticosteroid exposure, leading to Cushing's syndrome and adrenal suppression 1
• This interaction is well-documented and represents a serious safety concern requiring immediate regimen modification 1

Resistance Profile Considerations

This patient has extensive resistance requiring careful regimen selection:

• Resistant to all NRTIs, NNRTIs, maraviroc, and several first-generation PIs 1
• Currently virologically suppressed on darunavir (active PI) + elvitegravir (INSTI) + FTC/TAF backbone 1
• Must maintain darunavir given extensive PI resistance and current viral suppression 1
• Cannot switch to regimens with lower genetic barriers (like dolutegravir/lamivudine) given documented NRTI resistance 1

Why Option A is Superior

Bictegravir/FTC/TAF + darunavir/cobicistat addresses all key issues:

Eliminates the Problematic Interaction

• Bictegravir is metabolized via UGT1A1 and CYP3A4, but does not require pharmacologic boosting 2, 3
• B/F/TAF has minimal drug-drug interactions with CYP450-metabolized medications including corticosteroids 2, 4
• Removing elvitegravir (which requires cobicistat boosting) eliminates the fluticasone interaction 1, 2

Maintains Virologic Efficacy

• Preserves darunavir, which is essential given extensive PI resistance 1
• Bictegravir provides high genetic barrier INSTI activity 5, 3
• This combination (elvitegravir/cobicistat/FTC/TAF + darunavir) has demonstrated 90% viral suppression rates in patients with archived 2-class resistance 1

Addresses Comorbidities

• TAF is preferred over TDF for patients with osteoporosis (less bone density loss) 1
• No interaction with rosuvastatin (unlike some PIs) 4
• No interaction with risedronate or calcium/vitamin D 2

Why Other Options Are Inappropriate

Option B: Dolutegravir/lamivudine + atazanavir

• Contraindicated: Two-drug regimens are not recommended for patients with prior virologic failure and archived resistance 1
• Lamivudine alone provides inadequate NRTI coverage given documented NRTI resistance 1
• Atazanavir may not be active given "several first-generation PI" resistance 1

Option C: B/F/TAF + lenacapavir

• Removes darunavir, which is currently providing active PI coverage 1
• While lenacapavir has high barrier to resistance, insufficient data support switching from suppressive darunavir-based regimens in heavily treatment-experienced patients 1
• Unnecessarily complex with subcutaneous administration 1

Option D: B/F/TAF + fostemsavir

• Removes darunavir without clear justification 1
• Fostemsavir (attachment inhibitor) is typically reserved for heavily treatment-experienced patients with limited options, not as first-line switch strategy 1
• No evidence supports this combination over maintaining darunavir 1

Implementation Strategy

Specific switching approach:

1. Discontinue elvitegravir/cobicistat/FTC/TAF 1
2. Initiate B/F/TAF once daily 2, 6
3. Continue darunavir 800mg once daily (now without cobicistat, as bictegravir doesn't require boosting) 1
4. Check HIV RNA at 4 weeks post-switch to confirm maintained suppression 1

Important caveat: If darunavir requires boosting for this patient's specific resistance pattern, darunavir/cobicistat can be continued as a separate agent, but the fluticasone must be switched to a non-CYP3A4 metabolized alternative (like beclomethasone) or the patient must accept close monitoring for adrenal suppression. 1

Monitoring Requirements

• HIV RNA at 4 weeks post-switch, then every 3-6 months 1
• Monitor for resolution of adrenal suppression symptoms 2
• Continue bone density monitoring given osteoporosis and age 1
• Renal function monitoring (eGFR) given TAF use, though less concerning than TDF 1