Around 40 million people live with HIV-1 (the most common HIV strain) and while symptoms can now be better managed with lifelong treatment, there is no cure to fully eliminate the virus from the body. One of the most promising treatment avenues is disrupting HIV replication by impairing the function of integrase, a protein named for its role in integrating viral genetic material into the human host genome—but scientists have recently noticed that integrase also interacts with viral RNA to help the virus spread and infect new cells. Salk Institute researchers created novel 3D models of integrase in these distinct DNA and RNA roles, which can be used to connect the dots between integrase’s form and function to begin developing compounds that could impair distinct functions of integrase and, in turn, better treat people living with HIV.