Chronic immune activation is a central driver of HIV-1 infection and progression to AIDS (1, 2, 4–6), and can be partially attributed to the rapid and massive depletion of gastrointestinal CCR5+CD4+ T cells following infection (57, 58), which compromises the integrity of the mucosal barrier and facilitates translocation of bacteria from the gut (1, 2, 59). Here, CD4 is linked to infection.