DRUG-DRUG INTERACTION LEADING TO ADRENAL INSUFFICIENCY IN A PATIENT WITH HUMAN IMMUNODEFICIENCY VIRUS

Case Presentation: A 55-year-old man with a history of HIV previously on combination antiretroviral therapy (cART), hypertension, and COPD presented with hypotension. He had been on the combination antiretroviral elvitegravir-cobicistat-emtricitabine-tenofovir alafenamide (Genvoya) for approximately one year but had discontinued it 10 days prior. His last known CD4 count was 273 cells/ uL one month prior. He was compliant with his other medications including HCTZ/lisinopril and inhalers per his pulmonologist (tiotropium and fluticasone/vilanterol). He presented with a blood pressure of 60/40 mmHg, a pulse of 130 bpm, lactate of 3.7 mmol/L and WBC of 9.8 K/cmm. Due to concern for sepsis he was given IV antibiotics, IV fluids, and IV methylprednisolone and transferred to a higher level of care. On arrival, he had only mild symptoms to report and his blood pressure was 139/87 mmHg. A basic infectious evaluation was unremarkable.

Reviewing his medications, it was noted that the cobicistat contained in the cART that he had discontinued 10 days prior could inhibit the metabolism of fluticasone, which could lead to elevated serum steroid levels and subsequent adrenal suppression. The sudden removal of the cobicistat could result in an abrupt drop in serum steroid levels. An ACTH stimulation test was obtained, 0800 cortisol was 1.5 ug/dL which increased to 16 ug/dL after one hour. Endocrine consultants agreed that the transient hypotension was likely related to adrenal suppression from the cobicistat/fluticasone combination. He was started on hydrocortisone and inhaler changes were made.

Discussion: This is a unique case of a drug-drug interaction ultimately leading to a presentation of adrenal insufficiency. The combination of the cobicistat and inhaled fluticasone led to corticosteroid excess and adrenal suppression. The cobicistat in the combination cART drug is a potent CYP3A inhibitor, whose purpose is to increase or “boost” the levels of elvitegravir via CYP inhibition. This case is unusual in that the drug-drug interaction became clinically evident with the removal of the cART. The removal of the cART effectively decreased the level of circulating corticosteroid which resulted in hypotension that improved abruptly with steroids. It is notable that the culprit interacting drug was an inhaler, which can be overlooked as a potential interacting medication. Among the inhaled corticosteroids, fluticasone has been identified as most likely to result in significant steroid accumulation when used with cobicistat and should be avoided. Beclomethasone is not metabolized by CYP 3A4 and would be considered a safer option.

Conclusions: Antiretroviral medications that contain CYP3A inhibitors can decrease the metabolism of other drugs including inhaled corticosteroids, which can lead to clinically significant steroid excess and in this case, steroid deficiency with cART cessation.