Ritonavir is a powerful inhibitor of the cytochrome P450 3A4 (CYP3A4) isoenzyme. It is used as a pharmaceutical enhancer in the management of HIV-positive patients. However, when co-administered with other drugs that are metabolised via the CYP3A4 pathway, ritonavir can potentially cause serious drug-drug interactions. Inhaled fluticasone propionate, which is used to treat asthma and chronic obstructive airway disease, is particularly prone to such interactions due to its physiological attributes. We report a HIV-positive 48-year-old male patient who presented to Al Nahdha Hospital, Muscat, Oman, in 2012 with weight loss, generalised weakness and fatigue and diagnosed with secondary adrenal insufficiency as a result of concomitant ritonavir and inhaled fluticasone.