Iatrogenic Cushing's Syndrome in HIV-Infected Patients Receiving Ritonavir and Inhaled Fluticasone: Description of 4 New Cases and Review of the Literature

Abstract

Protease inhibitors boosted with ritonavir can lead to drug-drug interactions, particularly with inhaled corticosteroids such as fluticasone, because of the potent inhibition of cytochrome P450-3A4 activity. We report 4 cases of iatrogenic Cushing's syndrome after concomitant administration of inhaled fluticasone and antiretroviral therapy including a protease inhibitor boosted with ritonavir. Although typical manifestations were present, diagnosis of Cushing's syndrome was delayed because the patients were suspected to have antiretroviral therapy-associated lipodystrophy, which shares common clinical features with Cushing's syndrome. Biochemical tests confirmed iatrogenic Cushing's syndrome and clinical symptoms resolved after stopping ritonavir or fluticasone. The differences between the clinical symptoms of Cushing's syndrome and lipodystrophy are discussed as well as their frequency in the cases reported in the literature. The recommendation that concomitant administration of inhaled or intranasal fluticasone and ritonavir be prohibited must be implemented among practitioners who treat HIV-infected patients, and if long-term inhaled steroids are required, other drugs should be preferred.

Exogenous Cushing’s syndrome due to topical corticosteroid application: case report and review literature

“…The interaction between inhaled/intranasal Fluticasone and the potent Protease inhibitor, Ritonavir, in HIV infected patients are well documented causing Iatrogenic Cushing syndrome by the mention mechanism. Two series of systematic reviews were shown those effects in both adult and children [38,39]. The combination median time of treatment was 4 months and the duration for symptom correction was 3.6 months [40][41][42][43][44].…”

Iatrogenic Cushing's syndrome and osteoporosis due to an interaction between fluticasone and ritonavir

“…This has been reported elsewhere3 11 12 and, though the exact mechanism is not well-understood, the prolonged hyperglucocorticoid state is believed to activate T-lymphocyte apoptosis.…”

Nose and Sleep Breathing Disorders

“…Current antiretroviral regimens often contain the HIV protease inhibitor ritonavir, and co-administration with topical fl uticasone results in a dramatic increase in the latter bioavailability. This may result in iatrogenic Cushing's syndrome as alerted in increasing number of case reports (Mahlab-Guri et al 2011 ;Kedem et al 2010 ;Valin et al 2009 ;Samaras et al 2005 ). Ironically, in patients treated by ritonavir, older generations of topical glucocorticoids appear to be safer options (Foisy et al 2008 ).…”