Introduction: Is viral shedding a surrogate marker for transmission of genital herpes?

Genital herpes, caused by either herpes simplex virus type 1 or 2 (HSV-1 and HSV-2), is a significant public health problem worldwide. It increases the risk of infection with HIV, upregulates HIV after infection and can be associated with serious morbidity and mortality. It is now known that clinical and subclinical viral reactivation with resultant shedding from anogenital mucosa occurs frequently, resulting in transmission during sexual contact. Sexual transmission of HSV infection is common, even between monogamous individuals. Antiviral therapy reduces the frequency and degree of viral shedding and lowers the transmission rate in discordant monogamous couples, although transmission can still occur in people prescribed antiviral therapy. These encouraging data raise important questions for the management of genital HSV infection, particularly with regard to the prevention of transmission. Although the quantity of virus present is clearly important in transmission of some viruses, it is not clear whether this is the case for HSV transmission. Ideally, a surrogate marker needs to be able to identify individuals with detectable amounts of virus, and differentiate them from individuals with detectable amounts of virus that are transmissible. The aim of this supplement is to explore the issues surrounding the validation of surrogate markers of transmission of HSV, using examples from other human viral diseases, and to review the available evidence. In the future, exploration of these issues may shed light on management and prevention strategies. In particular, the results may clarify what evidence is required to warrant prescribing a drug for reducing HSV transmission, and for which patient populations this strategy is appropriate.