Abstract
(1) Background: Second-generation integrase strand transfer inhibitors (INSTIs) are now the preferred first-line therapies for human immunodeficiency virus (HIV). However, concerns regarding their side effects, such as weight gain and metabolic disturbances, have emerged. This scoping review aims to assess the effects of INSTIs on the gut microbiota, with a focus on differences between agents and their clinical implications. (2) Methods: A scoping review was conducted using PubMed, Web of Science, and Embase, with reports collected following PRISMA for Scoping Reviews (PRISMA-ScR). (3) Results: The majority of available evidence focused on dolutegravir, which demonstrated beneficial effects on microbiota diversity and composition. However, factors such as younger age, lower CD4+ counts, and extreme BMI were associated with proinflammatory changes. Limited data on bictegravir also suggested favorable alterations in the gut microbiota. Raltegravir, a first-generation INSTI, was associated with improvements in alpha diversity and microbial composition, although these changes were not consistently beneficial. Moreover, associated changes in inflammatory and microbial translocation markers suggested unfavorable alterations. (4) Conclusions: Based on the evidence mapped, second-generation INSTIs may generally induce favorable changes in the gut microbiota. However, further research is needed to explore the clinical implications of these microbiota alterations, particularly in specific patient groups.