Abstract

Introduction: CYP3A4 is the principal enzyme of cytochrome P450 and is the primary metabolic step for the degradation of corticosteroids. Cobicistat is a potent CYP3A4 inhibitor, it is used to increase the levels of antiretrovirals in the treatment of HIV. It is currently available as part of a fixed-dose combination, where it is used to enhance the integrase inhibitor elvitegravir. The interaction of CYP3A4 inhibitors and substrates can lead to numerous side effects. We present a case of drug-drug interaction resulting in adrenal insufficiency. Case: A 34 y/o male with PMH HIV and asthma comes to the office for evaluation of low cortisol noticed on an AM serum blood test, at the time of visit reported being evaluated by his HIV specialist for complaints of stretch marks and facial swelling; at the time of our evaluation these symptoms had resolved, but prompted further evaluation and a cortisol level 0.2 ug/dl was found. He was diagnosed with HIV in 2015 and since 2016 had been on HAART therapy with a combination of elvitegravir/cobicistat/emtricitabine/tenofovir (Genvoya); additionally, was recently started on a Breo-Ellipta inhaler which consists of fluticasone and vilanterol. During an initial assessment, the patient complained of fatigue and lightheadedness. He denied weakness, weight loss, nausea or vomiting. It was suspected that the etiology of these findings was due to a drug-drug interaction between cobicistat and the inhaled steroids, as this could be causing adrenal insufficiency secondary to the interference of steroid metabolism. On a follow-up visit, an ACTH stimulation test was scheduled, measures of serum cortisol remained at 0.2 ug/dl confirming the diagnosis. He was prescribed prednisone 5 mg daily. Patient was recommended to suspend his inhaler and follow up with a pulmonologist. After discontinuing inhaled steroids, initial symptoms gradually improved, repeat ACTH stimulation test a month later showed regain of adrenal function. He is currently asymptomatic. Conclusion: This case report highlights the importance of recognizing potential interactions between medications in patients with chronic diseases. Clinicians should continuously consider drug-drug interactions when prescribing enzyme inhibitors; currently, the majority of the literature available focuses on protease inhibitors and less on integrase inhibitors. The management of patients with HIV and asthma requires an interdisciplinary approach to improve outcomes.

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