How genetically simple pathogens like HIV overwhelm complex immune systems is not fully understood. One unexplored possibility is that epistatic interactions across genetically complementary quasispecies (i.e., group-level social heterosis) allow pathogens to escape immune suppression. We tested this hypothesis by simulating an " HIV-like " pathogen under simultaneous individual-and group-level selection. Results matched in vivo HIV infection patterns, with virulence correlating to intrahost viral diversity patterns, variable times to immune system collapse extrinsic to variation in host immunity, unchanging viru-lence across infections, repeated evolution of complementary quasispecies clades, and numerous reversion mutations after virus transmission. Thus when group selection drives pathogen evolution, studying individual clones or consensus sequences will miss the possible effects of genetically synergistic " social genomes " on virulence. Furthermore, results suggest that virulence is reducible by manipulating selection to favor individual-level competitive ability in viruses. Overall, social genome models of pathogen interaction could produce novel approaches in studying diseases.