Extreme Iatrogenic Cushing's syndrome in HIV-infected patient as a result of the interaction between Ritonavir and inhaled Fluticasone

Introduction: Ritonavir is a protease-inhibitor (PI) commonly used in the treatment of HIV-infected patients because of its potent inhibition of cytochrome P450 (CYP) 3A4 activity. This leads to a significant increase in the PI co-medication levels and therefore to an improvement of their clinical efficacy. However, ritonavir could lead to other relevant drug-drug-interactions, when the metabolism of such drugs depends on the cytochrome P450 (CYP) 3A4. The co-administration of ritonavir and inhaled fluticasone results in an increase in the plasma corticosteroid levels and consequently in an iatrogenic Cushing's syndrome.

Case: We report about a 46-year-old HIV-infected patient, who presented with typical Cushing stigmata. A few months earlier an excavation of the sella region had been detected in a routine CT of the head. As the Cushing symptoms occurred, it has been suspected that the patient presents with Cushing's disease. However, the biochemical tests indicated an iatrogenic Cushing's syndrome. The only prescribed steroid was inhaled fluticasone as therapy of COPD. The patient consulted numerous physicians until a drug-drug-interaction between her HIV-therapy with ritonavir and the inhaled fluticasone was suspected. At this point the patient had developed a severe CMV and pseudomonas pneumonia due to patient's compromised immune system. Consequently, fluticasone was stopped and a temporary prophylactic hydrocortisone therapy was initiated.

Discussion: Inhaled steroids in the treatment of asthma or COPD do not usually lead to relevant systemic adverse events. However, drug-drug-interactions such those between ritonavir and inhaled steroids can occur and cause iatrogenic Cushing's syndrome, which could lead to severe complications. We suspect that such adverse events are underdiagnosed and recommend caution when treating patients with both inhaled steroids and ritonavir. In these cases the stopping of either ritonavir or inhaled steroids should be considered.