Early events in sexual transmission of HIV and SIV and opportunities for interventions

To constrain the growth of the HIV/AIDS pandemic and ultimately end it, effective measures must be developed to prevent sexual mucosal transmission, the major route by which new infections are acquired. I review sexual mucosal transmission of HIV and SIV, with a focus on vaginal transmission in the SIV rhesus macaque animal model, and the evidence for small founder populations of infected cells and the local expansion at the portal of entry necessary to establish systemic infection. These early events represent windows of maximum opportunity for interventions to prevent systemic infection. I highlight the paradoxical role the innate immune response plays in actually facilitating transmission, and a novel microbicide strategy that targets this innate response to prevent systemic infection, and I conclude with an agenda for future research that emphasizes mucosal immunology, virology and pathogenesis studies at each anatomic site of entry.