XZ426 is a potent integrase strand transfer inhibitor with anti- HIV activity.In Vitro:Intasomes are the target of the latest generation of antiretroviral drugs, integrase (IN) strand transfer inhibitors (INSTI). To better understand how INSTIs interact with HIV intasomes, we assembled the complex with bictegravir (BIC), the leading second-generation INSTI and the most broadly effective of all clinically approved INSTIs. Among these, XZ426 is a lead candidate that has shown superior efficacy to all clinically used and developed compounds against known drug-resistant variants.