MON-887 - A Case of Genvoya Induced Cushing Syndrome

Introduction: Boosted antiretroviral therapy is widely used in HIV management, the two boosting agents being ritonavir and cobicistat. Both cause potent CYP3A4 inhibition that can markedly increase systemic exposure to co-administered drugs, including inhaled corticosteroids such as fluticasone. Because boosting agents—particularly cobicistat—are often co-formulated within single-tablet regimens, it may not be immediately apparent that a patient is receiving one. This interaction can lead to iatrogenic Cushing syndrome and secondary adrenal insufficiency. Although described in the literature, it is still sometimes overlooked in clinical practice. Awareness is essential to prevent avoidable morbidity.

Case Presentation: A 76-year-old man with well-controlled HIV on Genvoya and asthma was started on inhaled fluticasone. After several months, he developed progressive facial rounding, supraclavicular fat pads, and fatigue. Laboratory evaluation showed a undetectable morning cortisol, low ACTH (2.3 pg/mL), and low DHEA-S (9.5 µg/dL). Bone density testing revealed osteopenia. The findings were consistent with iatrogenic Cushing syndrome due to elevated systemic fluticasone levels from cobicistat-mediated CYP3A4 inhibition. Genvoya was discontinued and replaced with Biktarvy, allowing continuation of fluticasone. Physiologic hydrocortisone replacement was initiated. Over subsequent months, his Cushingoid features improved, but biochemical suppression of the hypothalamic–pituitary–adrenal axis persisted, requiring continue physiologic hydrocortisone replacement.

Discussion: This case highlights an important interaction between cobicistat-containing antiretroviral therapy and inhaled fluticasone. Cobicistat, as well as ritonavir, produces potent CYP3A4 inhibition that can substantially increase systemic corticosteroid exposure, leading to iatrogenic Cushing syndrome and adrenal suppression. Although recognized in the literature, this interaction can still sometimes be missed, especially since the booster is co-formulated within a single tablet, resulting in delayed diagnosis and preventable morbidity. Early recognition, adjustment of antiretroviral therapy and or co-administered drugs, and monitoring for secondary adrenal insufficiency are essential for safe management.

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