While HIV replication and CD4+ T-cell depletion lead to increased gut permeability, microbial translocation, chronic immune activation, and systemic inflammation, the natural hosts of SIVs generally avoid these deleterious consequences when infected with their species-specific SIVs and do not progress to AIDS despite persistent lifelong high viremia due to long-term coevolution with their SIV pathogens. The gene discussed is CD4; the disease is AIDS.