Indeed, the first line of defense could be represented by soluble antiviral factors naturally produced in HESNs in higher amounts such as CAMP, PI3, SLPI, and defensins (3–8), which act inhibiting HIV-1 infection directly interacting with virions and through enhancement of specific anti-HIV-1 cellular mechanisms, thus preventing productive infection locally at the transmission site. This evidence concerns the gene SLPI and HIV-1 infection.