Despite the widespread availability of antiviral drugs the worldwide epidemic of genital herpes continues. HSV-2 increases the rate of acquisition of HIV-1 2-fold, the efficiency of transmission of HIV-1 5-7 fold, increases maternal to child transmission of HIV-1 and raises HIV plasma viral load by 0.5 logs. In the U.S. neonatal herpes now ranks as the infectious disease of greatest morbidity and mortality to the neonate in which no prevention strategy exists. Our recent studies have begun to provide the underlying biological mechanism for these epidemiological associations between HSV and HIV. The pace of reactivation and clearance of HSV infections is 10 fold "quicker" than previously appreciated; over 50% of mucosal HSV-2 reactivations last