Although 85% of new HIV cases are due to sexual transmission from men to women, little attention is being paid to the immune system in the female reproductive tract (FRT), and to how it meets the conflicting challenges of protecting from pathogens and permitting procreation. As a new approach we have tried to envision how HIV evades FRT mucosal immune protection and have been led to the unexpected conclusion that in a normal menstrual cycle, there is a window of vulnerability (7–10 days following ovulation) in which the potential for viral infectivity in the FRT is enhanced. During that period, aspects of the innate, humoral, and cell-mediated immune systems are suppressed by sex hormones to optimize conditions for procreation. Suppression occurs in the upper (Fallopian tubes, uterus, endocervix) and lower (ectocervix and vagina) FRT, and coincides with the recruitment of potentially infectable cells and upregulation of coreceptors essential for viral uptake. Implications of these findings are that the entire FRT is a potential target for HIV infection, immune cells and antibodies in blood are not surrogate markers for immune protection in the FRT, and immune protection against HIV will require an understanding of the hormone-induced regulation of humoral, cellmediated, and innate immune systems throughout the FRT.

The need to understand the interplay between the immune and endocrine systems in the human female reproductive tract Despite unprecedented efforts by scientists worldwide, the solution to the ever-growing HIV/AIDS crisis remains elusive. HIV/AIDS is unique in modern human history in its rapid spread, its extent, and the depth of its impact. Since the first AIDS case was diagnosed in 1981, the world has struggled to come to grips with its extraordinary toll. Approaching 25 million deaths worldwide with an additional 33.2 million (of which 15.4 million are women) estimated to be infected worldwide, HIV/AIDS will soon be the world’s worst pandemic [1].