Three Integrase (IN) strand transfer inhibitors are in intensive clinical use, raltegravir, elvitegravir anddolutegravir. However, the onset of IN resistance mutations limits their therapeutic efficiency. As put forth earlier, the drug affinity for the intasome could be improved by targeting preferentially the retroviralnucleobases, which are little, if at all, mutation-prone. We report experimental results of anisotropy fluorescence titrations of viral DNA by these three drugs . These show that the ranking of their inhibitory activities of the intasome corresponds to that of their free energies of binding, D Gs,to retroviral DNA, and that such a ranking is only governed by the binding enthalpies, D H, the entropy undergoing marginal variations.This ranking can therefore be directly correlated to that of model Quantum Chemistry (QC) calculations of intermolecular interaction energies of the sole halobenzene ring with the highly conserved retroviral nucleobases G4 and C14, using Density Functional Theory. This DE(QC) ranking is in turn reproduced by the corresponding DE tot values computed with a polarizable molecular mechanics/dynamics procedure, SIBFA (Sum of Interactions Between Fragments Ab initio computed). Such validations should enable polarizable molecular dynamics simulations on more potent inhibitors in their complexes with the complete intasome. Such derivatives should principally encompass modified halobenzene rings.