[1007] SAFETY AND EFFICACY OF BOSENTAN IN PULMONARY ARTERIAL HYPERTENSION ASSOCIATED WITH HIV INFECTION

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] SAFETY AND EFFICACY OF BOSENTAN IN PULMONARY ARTERIAL HYPERTENSION ASSOCIATED WITH HIV INFECTION

[AUTHOR(S):] M Opravil¹, O Sitbon², V Gressin³, R Speich¹, PS Macdonald⁴, DA Cooper⁴, M Rainisio³, JF Delfraissy² and G Simonneau²
¹University Hospital Zurich, Switzerland; ²Hôpital Antoine Béclère, Clamart, France; ³Actelion Pharmaceuticals Ltd; and ⁴ St Vincent’s Hospital, Sydney, Australia

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 1007
Antiviral Therapy 2003; 8(Suppl. 1):S469

[ABSTRACT:] The endothelin receptor antagonist bosentan is a novel therapy for pulmonary arterial hypertension (PAH). PAH occurs as a cardiovascular complication in 0.2–0.5% of human immunodeficiency virus (HIV)-infected patients, significantly increasing mortality. Histological similarities with primary PAH, including increased endothelin expression, suggest patients with PAH associated with HIV could benefit from bosentan therapy. Preliminary results are reported for 10 patients from an ongoing open-label study. Patients with HIV and NYHA functional class III PAH received bosentan for 16 weeks (62.5 mg bid for 4 weeks; thereafter 125 mg bid) with stable (>3 months) antiretroviral therapy. Patients with portal hypertension, cirrhosis or liver enzymes >3 x upper limit of normal were excluded. Safety was assessed by CD4 cell count, viral load, liver function and adverse events. Efficacy was assessed by exercise capacity, NYHA class and haemodynamics (right heart catheterisation). Mode of HIV contamination varied (sexual: 6; transfusion: 1; unknown: 3) for the 10 patients (mean age 42 years; 6 male; 9 HAART), as did CDC class (A: 4; B: 3; C: 3). Baseline median counts of CD4 cells were 286 cells/mm³; 5 of 8 patients had an undetectable viral load (HIV-RNA <400 copies/ml). After 8 weeks there were no relevant changes in CD4 count or the number of patients with suppression of HIV-1 RNA, suggesting no relevant effect of bosentan on control of HIV infection. No change in liver enzymes was associated with bosentan. Adverse events included cramps (n=2), headaches (n=2), vertigo (n=1), leg oedema and/or weight gain (n=3), which improved with diuretics. Patients improved their 6-minute walk distance from 361±68 to 443±54 m (n=9; P<0.050), NYHA class (9 improved to Class I or II; 1 remained in Class III) and cardiac index (2.5±0.6 to 3.5 ± 0.6 l/min/m²; P<0.050). Significant decreases in pulmonary vascular resistance (784±277 to 456±263 dyn.sec/cm⁵; P<0.001), and mean pulmonary arterial pressure (50.1±10.4 to 42.0±16.2 mm Hg; P<0.050) were also observed. No patient died, required epoprostenol therapy or hospitalization for PAH. These preliminary results suggest that bosentan improves PAH symptoms and haemodynamics, can be given concomitantly with antiretroviral therapy, and is well-tolerated in patients with PAH associated with HIV.

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