The HIV protease inhibitors saquinavir, ritonavir, and nelfinavir but not indinavir impair the epithelial barrier in the human intestinal cell line HT-29/B6

HIV protease inhibitors (PI) effectively suppress HIV replication and decrease HIV-related morbidity and mortality. These effects, however, require high compliance of patients and may therefore be seriously hampered by adverse effects. Diarrhoea is a common adverse effect of PI and occurs in 16-62% of patients. The pathogenesis of diarrhoea elicited by PI is unknown. Apart from abnormal intestinal motility and malabsorption, diarrhoea can be driven by increased active ion secretion (secretory diarrhoea) or by the passive back-leak of ions caused by a diminished epithelial barrier function (leak-flux diarrhoea). We therefore examined the effects of PI on the secretion and barrier function in the colonic epithelial cell line HT-29/B6.