A successful treatment of Human immunodeficiency virus (HIV) infection accompanied by a complete restoration of gut dysbiosis is of great interest in order to avoid activation of the mucosal immune system, persistent inflammation and the development of long-term complications.

Integrase strand transfer inhibitors (INSTIs) are the preferred choice as part of the first-line regimen in treatment-naïve individuals.

The role of INSTIs in gut microbiota in the context of HIV infection has not yet deeply investigated.

INSTIs-based treatments (dolutegravir and bictegravir) were able to restore the impact of HIV infection on bacterial translocation, systemic inflammation, gut permeability and bacterial richness/diversity.

These results suggest a protective role of current INSTIs regimens in disease progression, subsequent immune activation and in the development of future dysbiosis-related complications.