Missing out on the biology of heterosexual HIV-1 transmission.

Although unprotected heterosexual intercourse is recognized as the primary mechanism sustaining the global spread of HIV-1, many fundamental details surrounding transmission and establishment of primary HIV-1 infection remain unresolved. Unprotected intercourse induces widespread changes in female reproductive tissues linked to immediate removal of excess spermatozoa and preparation of the uterus for implantation. Concurrently, contact with semen may transiently increase susceptibility to HIV-1 by perturbing mucosal barrier function and triggering localized inflammation. In this manner, infectious HIV-1 in semen becomes an adventitious traveler on the pathway leading to normal human reproduction. This review summarizes key elements of male-to-female HIV-1 transmission and presents a rationalization for human-based studies to illuminate the biology of heterosexual HIV-1 transmission.