Effects of different antiretroviral treatments on gut microbiota of hiv-infected patients stars

Resum

The human gut microbiota has a symbiotic relationship with the host and plays a crucial role in the maintenance of health. HIV infection has been associated with a disturbance in gut microbiota (dysbiosis). Increased bacterial translocation and alterations to gut microbiota composition have been observed in HIV-infected patients and contribute to immune activation and inflammation. This Doctoral Thesis demonstrates, in clinical practice, that not only HIV infection has effects on gut physiology and microbial profile, but also different combined antiretroviral therapies modify gut microbiota composition. From all the combinations tested in this study, INSTI-based antiretroviral therapy was associated with levels of systemic inflammation and bacterial translocation similar to uninfected controls, suggesting a healthier gut and potentially lesser HIV-related complications. In vitro, Maraviroc did not exert any bacteriostatic effect in the tested strains, and no significant effects were either found in gut microbiota composition when administered to mice fed a standard diet, while several and interesting actions were observed when administered to high-fat diet fed-mice. Although Maraviroc is not actually prescribed as monotherapy, if its immunological actions could be potentiated if administered along with a high fat diet deserves further investigation. Finally, we have also demonstrated that other factors that increase the morbidity and mortality of these patients, such as the coinfection with hepatotropic viruses and the metabolic syndrome, also affects the gut flora, although to a lesser extent than HIV infection itself. However, these effects are not mild and highlight the need for monitoring these patients even after immunological control with combined antiretroviral therapies.