Comparison of Efavirenz and Dolutegravir on Gut Microbiome and Gut Barrier Functions

Dolutegravir (DTG) is increasingly replacing efavirenz (EFV) as the recommended first-line antiretroviral therapy (cART) component due to its superior tolerance. However, both EFV-based and DTG-based cART regimens are associated with metabolic and neuropsychiatric disorders through mechanisms that remain poorly understood. In this study, the abundance of Lactobacillus was significantly reduced, along with elevated soluble CD14 levels, in HIV-1-infected individuals receiving EFV-based cART compared to those on DTG-based cART. Additionally, EFV treatment in mice resulted in the destruction of intestinal crypts, loss of goblet cells, decreased expression of intestinal ZO-1, and more severe damage to gut barrier integrity compared to the DTG and normal control groups. Furthermore, we identified a significant reduction in Lactobacillus in EFV-treated mice. Our results suggest that EFV and DTG may directly lead to gut dysbiosis and compromised gut barrier integrity, which could be targeted to prevent the side effects associated with EFV and DTG.