Integrin α4β7 as a predictor of HIV acquisition: one thread in a complex tapestry

Cellular susceptibility to HIV is associated with integrin α4β7, a mucosal homing receptor involved with trafficking HIV target cells to sites of HIV replication. However, studies investigating preinfection α4β7 expression as a predictor of HIV outcomes have yielded inconsistent findings, raising questions about the role of α4β7 in HIV acquisition across populations. In this issue of the JCI, Machmach et al. assessed PBMCs collected before HIV infection and found higher α4β7 expression on memory CD4+ T cells and invariant NK T (iNKT) cells in individuals who went on to acquire HIV. Here, we consider possible explanations that may underlie discrepancies among studies and suggest that α4β7 should be considered as part of a multifactorial profile for determining HIV risk. While unlikely to serve as a target for HIV prevention or therapy, α4β7-directed interventions may offer adjunctive benefits in preserving or improving mucosal immunity.