Sildenafil is increasingly used for the therapy of pulmonary arterial hypertension (PAH) in HIV infected patients. However, concerns exist about pharmacokinetic interactions between sildenafil and protease inhibitors (PI); in particular, ritonavir has been shown to increase sildenafil AUC and Cmax by several folds. The aim of our study was to determine the plasma levels of sildenafil and PI in two HIV patients with PAH treated with antiretroviral therapy including ritonavir-boosted PI. Our patients both experienced sildenafil Cmax above 500 ng/mL; however, they did not report any significant adverse reactions to sildenafil during the follow-up period. Therapeutic drug monitoring of sildenafil should be taken in consideration during treatment in order to avoid overdosage.