Bosentan and sildenafil in the treatment of HIV-associated pulmonary hypertension

We present the case of an HIV/HCV-coinfected patient with HIV-related pulmonary hypertension (HRPH) who experienced a good clinical and functional response to bosentan, with a subsequent switch to oral sildenafil due to increased transaminase levels. Bosentan resulted less handy in this case, probably due to both side effects and co-morbidities

Sildenafil and bosentan plasma concentrations in a human immunodeficiency virus-infected patient with pulmonary arterial hypertension treated with ritonavir-boosted protease inhibitor

Sildenafil and bosentan are increasingly used for the treatment of pulmonary arterial hypertension (PAH) in HIV-infected patients. However, concerns exist about pharmacokinetic interactions among sildenafil, bosentan and antiretroviral drugs, including protease inhibitors (PI). We describe here the case of an HIV-infected patient with PAH, who was co-administered bosentan 125 mg twice daily and sildenafil 40 mg three times per day, together with a ritonavir-boosted PI-based antiretroviral therapy; plasma levels of bosentan, sildenafil, N-desmethylsildenafil, and PI were measured. The patient had a sildenafil Cthrough and Cmax of 276.94 ng/mL and 1733.19 ng/mL, respectively. The Cthrough and the Cmax of bosentan were 1546.53 ng/mL and 3365.99 ng/mL, respectively. The patient was able to tolerate as high sildenafil blood concentrations as 10 times those usually requested and did not report any significant adverse reaction to sildenafil during the follow-up period. Therapeutic drug monitoring should be considered during sildenafil therapy in patients concomitantly treated with ritonavir-boosted PI

Realignment of the ventricular septum using partial direct closure of the ventricular septal defect in Tetralogy of Fallot

OBJECTIVE: The aim is to describe our technique of partial direct closure of the ventricular septal defect (VSD) in Tetralogy of Fallot (TOF), and assess its influence on the realignment and remodeling of the left ventricular outflow tract. METHODS: Between 2004 and 2010, 32 non-consecutive patients with TOF underwent a direct or partial direct closure of VSD. Median age and weight were 5.2 months and 6.7 kg, respectively. An approach through the right atrium was used in 30 patients and through the infundibulum in two patients. The conal septum was mobilized by transecting the hypertrophic trabeculae to facilitate the approximation of the VSD. The membranous part of the VSD was closed (in the later part of the series) with a small xenopericardial patch to avoid tension on the suture line traversing the area of risk to the bundle of His. Follow-up was complete, with a median duration of 46.9 (range 12-75.3) months. RESULTS: The VSD could be closed successfully in all patients. A residual VSD was partly responsible for one early postoperative re-operation. There were no early or late deaths. At follow-up, all patients were in sinus rhythm. Three patients showed a small residual VSD. Thirty patients had none, one showed trivial, and one had mild aortic regurgitation. The left ventricular outflow showed a good realignment of the ventricular septum in all the patients. CONCLUSIONS: Partial direct closure of the VSD corrects the primary defect in TOF, that is, the malalignment of the septum. It results in a straight, wide open left ventricular outflow tract and brings better support to the aortic root