We have described an interface between the QUBEKit force field engine, and the Sire molecular simulation framework, for the calculation of alchemical relative binding free energies. As an example application, we have retrospectively analyzed the binding of 22 small molecule inhibitors of HIV-1 reverse transcriptase. With the significant caveat that EC 50 is not a direct measurement of binding, it appears that the QUBE/SOMD interface is capable of providing a useful guide in design efforts. Where computational and experimental trends in binding are not in agreement, the simulations tend to be characterized by high hysteresis.