Tu2024 AIEC Instigates Chronic Colitis by Altering Microbiota Composition and Its Inherent Pro-Inflammatory Potential

Abstract

Background. The protease inhibitor ritonavir is part of highly active anti-retroviral therapy (HAART) used successfully in the treatment of human immunodeficiency virus (HIV) infection. There is evidence that ritonavir alters intestinal permeability and induce damage to the small intestine. Because HIV infected patients taking HAART are at high risk of developing cardiovascular complications, there might be a need to use low dose of aspirin (ASA) to prevent inschemic event. Similarly, long term survival exposes HIV infects persons to detrimental interaction of ritonavir with NSAIDs, since both agents might cause intestinal injury. Aims. To test whether ritonavir worsens intestinal injury caused by NSAIDs and ASA. Methods. C57BL6 mice were treated for 25 days with ritonavir (50 mg/Kg/day per os) and than for others 5 days with the combination of ritonavir plus ASA (50 mg/Kg/day per os) or naproxen (100 mg/Kg/day per os). In a second set of experiments C57BL6 mice were treated for 25 days with ritonavir (50 mg/Kg/day per os) alone or in combination with the PGE2 analog misoprostol (100 μg/Kg per os). Results. Ritonavir administration per se caused intestinal damage and its co-administration in combination with naproxen or ASA exacerbated the severity of intestinal damage and intestinal inflammation as assessed by measuring haematocrit, MPO activity, relative mRNA expression of iNOS, MCP-1 and VLA-1 (Figure). All treatments caused reduced mucosal PGE2 . Co-administration of misoprostol, a PGE2 analogue, protected against intestinal damage induced by naproxen and ritonavir. Conclusions. The protease inhibitor ritonavir causes intestinal damage and its association with NSAIDs or ASA worsens damage caused by the COX-inhibitors. Misoprostol protects from damage caused by ritonavir. Further studies are need to clarify whether this observation has a clinical readout.