Iatrogenic Cushing's Syndrome: The Result of Cobicistat and Glucocorticoid Interaction in an HIV Patient After Bariatric Surgery

by Selleckchem | Mar 27 2023

Cobicistat, used as a pharmacokinetic booster in therapeutic combination with human immunodeficiency virus (HIV) protease inhibitors and integrase inhibitors, is a strong inhibitor of cytochrome P450 3A4 (CYP3A4). Since most glucocorticoids are metabolized by the isoenzyme of the cytochrome P450 pathway, their plasma concentrations can be highly increased in the presence of cobicistat-boosted darunavir, with subsequent risk of iatrogenic Cushing's syndrome (ICS) and secondary adrenal insufficiency. We report a case of a 45-year-old man with HIV-hepatitis C virus co-infection treated with raltegravir and darunavir/cobicistat since 2019. In May 2021, he underwent a sleeve gastrectomy due to morbid obesity (BMI: 50.9 kg/m2) with multiple comorbidities. Four months after surgery, he was diagnosed with asthma and was started on inhaled budesonide, which was later changed to fluticasone propionate. At the 12-month postoperative visit, the patient referred proximal muscle weakness and asthenia, and suboptimal weight loss (excess weight loss of 39%) and high blood pressure were documented. Moon facies, buffalo hump, and abdominal large vinous striae were evident on physical examination. Laboratory studies showed impaired glucose metabolism and hypokalemia. Cushing's syndrome was suspected and further investigation confirmed its iatrogenic origin. The diagnosis of ICS and consequent secondary adrenal insufficiency due to an interaction between the darunavir/cobicistat combination and budesonide/fluticasone was established. Darunavir/cobicistat therapy was replaced by dolutegravir/doravirine dual therapy, inhaled corticoid was switched to beclomethasone, and glucocorticoid substitutive therapy was introduced. This is a particular case of overt ICS due to cobicistat-inhaled corticosteroid interaction in a superobese patient, developed after he underwent bariatric surgery. The presence of morbid obesity, combined with the rarity of this pharmacological complication in individuals taking cobicistat, made the correct diagnosis even more challenging. A meticulous review of pharmacologic habits and potential interactions is essential to avoid serious harm to patients.

Comments：

The case report describes a 45-year-old man with HIV-hepatitis C virus co-infection who underwent sleeve gastrectomy for morbid obesity and was subsequently diagnosed with iatrogenic Cushing's syndrome (ICS) and secondary adrenal insufficiency. The patient was receiving cobicistat-boosted darunavir and was started on inhaled budesonide for asthma, which was later changed to fluticasone propionate. The interaction between cobicistat and inhaled corticosteroids caused a significant increase in the plasma concentration of the corticosteroids, leading to the development of ICS.

The diagnosis of ICS was challenging due to the patient's superobesity and the rarity of this pharmacological complication in individuals taking cobicistat. The patient presented with proximal muscle weakness and asthenia, suboptimal weight loss, high blood pressure, moon facies, buffalo hump, and abdominal large vinous striae. Laboratory studies showed impaired glucose metabolism and hypokalemia. Further investigation confirmed the iatrogenic origin of the patient's Cushing's syndrome.

The management of ICS involved replacing darunavir/cobicistat therapy with dolutegravir/doravirine dual therapy, switching to beclomethasone for inhaled corticosteroids, and introducing glucocorticoid substitutive therapy. A meticulous review of pharmacologic habits and potential interactions is essential to avoid serious harm to patients.

In conclusion, healthcare providers should be aware of the potential interaction between cobicistat-boosted darunavir and inhaled corticosteroids, which can lead to ICS in susceptible patients. A thorough evaluation of the patient's medical history, medication use, and potential drug interactions is crucial to prevent harm and ensure optimal patient care.