Current Thinking on Genital Herpes

Annika M. Hofstetter; Susan L. Rosenthal; Lawrence R. Stanberry


Curr Opin Infect Dis. 2014;27(1):75-83. 

In This Article

Abstract and Introduction


Purpose of review Genital herpes has a high global prevalence and burden of disease. This manuscript highlights recent advances in our understanding of genital herpes simplex virus (HSV) infections.

Recent findings Studies demonstrate a changing epidemiological landscape with an increasing proportion of genital herpes cases associated with HSV type 1. There is also growing evidence that the majority of infected individuals exhibit frequent, brief shedding episodes that are most often asymptomatic, which likely contribute to high HSV transmission rates. Given this finding as well as readily available serological assays, some have proposed that routine HSV screening be performed; however, this remains controversial and is not currently recommended. Host immune responses, particularly local CD4+ and CD8+ T cell activity, are crucial for HSV control and clearance following initial infection, during latency and after reactivation. Prior HSV immunity may also afford partial protection against HSV reinfection and disease. Although HSV vaccine trials have been disappointing to date and existing antiviral medications are limited, novel prophylactic and therapeutic modalities are currently in development.

Summary Although much remains unknown about genital herpes, improved knowledge of HSV epidemiology, pathogenesis and host immunity may help guide new strategies for disease prevention and control.


Genital herpes infection, caused by herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2), leads to significant morbidity and mortality worldwide. Although most infected individuals are asymptomatic, there may be severe clinical manifestations, especially in populations with underlying immune compromising conditions.[1–3] Individuals also have a range of psychological reactions to the diagnosis; for some, worries about telling partners and the impact on their sexuality are quite significant, particularly immediately after diagnosis.[4–6] In addition, genital herpes can be perinatally transmitted and cause life-threatening neonatal HSV infection.[7] Moreover, it increases the risk of HIV acquisition by two to three-fold as well as HIV transmission in dually infected individuals.[8,9–13] This high burden of disease makes global prevention and treatment of genital herpes infection critical. However, this has been challenging given recent epidemiological trends, limited knowledge of key aspects underlying HSV pathogenesis and immunobiology, and the lack of antiviral strategies that can completely eradicate latent infection or inhibit viral reactivation and recurrent infection. This review article describes the changing epidemiology of genital herpes infection and examines current understanding of HSV pathogenesis, focusing on reactivation and reinfection, and host immunity. This article also discusses HSV screening controversies and highlights previous, existing and forthcoming therapeutic and prophylactic modalities targeting HSV.