Date of report 26 Jun 2025

Reported case interaction between
Cobicistat and Epleronone

A cisgender man diagnosed with HIV in 2005, with a concomitant diagnosis of chronic hepatitis B virus (HBV) coinfection, initiated antiretroviral therapy (ART) in 2008 due to severe immunosuppression (nadir CD4 count: 60 cells/µL). The initial regimen included efavirenz/emtricitabine/tenofovir disoproxil fumarate, resulting in good virological and immunological responses.

In 2018, the patient required hospitalization for tuberculosis with pleural and pericardial involvement following an interruption of ART. During this admission, he developed nosocomial methicillin-resistant Staphylococcus aureus (MRSA) endocarditis, which led to severe aortic valve regurgitation. Due to heart failure associated with left ventricular dysfunction secondary to the valve disease, aortic valve replacement was performed in January 2020.

In February 2023, the patient’s cardiologist initiated low-dose eplerenone (12.5 mg once daily). At that time, he was receiving a fixed-dose combination of darunavir/cobicistat/emtricitabine/tenofovir alafenamide. From February 2023 to December 2024, he continued this combination without any reported adverse effects, including hyperkalaemia or other complications.

Notably, the coadministration of eplerenone with darunavir/cobicistat is contraindicated. Eplerenone is metabolized via CYP3A4, and plasma concentrations may rise substantially due to CYP3A4 inhibition by cobicistat, increasing the risk of eplerenone-related adverse events such as hyperkalaemia. In this case, the absence of toxicity may be attributed to the low dose of eplerenone.

Nevertheless, in December 2024, ART was switched to bictegravir/emtricitabine/tenofovir alafenamide to mitigate the risk of drug–drug interactions, particularly if an increase in the eplerenone dose became necessary.