Optimal Antiretroviral Regimen Change to Minimize Drug Interactions

Introduction to Antiretroviral Therapy

The American Medical Association recommends bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) combined with darunavir/cobicistat as the best regimen change to minimize drug interactions, as this maintains a 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, 2

Cobicistat is a potent CYP3A4 inhibitor that dramatically increases systemic corticosteroid exposure, leading to Cushing's syndrome and adrenal suppression, which is a serious safety concern requiring immediate regimen modification 1, 2, 4, 5

Patients with extensive resistance, including resistance to all NRTIs, NNRTIs, maraviroc, and several first-generation PIs, require careful regimen selection to maintain virologic efficacy 1, 2
The current regimen of darunavir (active PI) + elvitegravir (INSTI) + FTC/TAF backbone has demonstrated 90% viral suppression rates in patients with archived 2-class resistance, and darunavir must be maintained given extensive PI resistance and current viral suppression 1, 2, 6

TAF is preferred over TDF for patients with osteoporosis, as it results in less bone density loss 4, 5
The combination of B/F/TAF and darunavir has minimal drug-drug interactions with CYP450-metabolized medications, including corticosteroids, and does not interact with rosuvastatin, risedronate, or calcium/vitamin D 1, 2, 3, 4, 5, 6

The specific switching approach involves discontinuing elvitegravir/cobicistat/FTC/TAF, initiating B/F/TAF once daily, continuing darunavir 800mg once daily, and checking HIV RNA at 4 weeks post-switch to confirm maintained suppression 1, 2, 4, 5

HIV RNA should be monitored at 4 weeks post-switch, then every 3-6 months, and patients should be monitored for resolution of adrenal suppression symptoms, bone density, and renal function (eGFR) given TAF use 1, 2, 3, 4, 5, 6