Clinically documented mutant strains correspond to low energy (high fitness) states within our inferred model. Circles: Energies assigned by our model to the 10 p24 single mutants, 8 p24 double mutants, and 5 p17 double mutants listed within Table S1, which identifies the particular mutants, HLA associated epitopes, and computed energies. Squares: Energies of the strains of three p17 epitopes observed to undergo sequence adaptation in longitudinal deep sequencing of an HIV infected host (Henn et al., 2012). In all cases, residues outside the epitope are treated as wild-type in the assignment of energies.