Vaccine and Infectious Disease Division

The consequences of antiviral therapy on herpesvirus shedding

Herpes simplex virus 2 (HSV-2) is a sexually transmitted disease that can cause genital ulcers as a result of viral reactivation from a latent state. In addition, HSV-2 frequently reactivates and sheds even when clinical ulcerations are not present. A majority of these shedding episodes are of short duration (as brief as 1 hour), and because they are frequently asymptomatic, HSV-2 can be transmitted between sexual partners even when no indications of active disease are present. Preventative drugs exist for HSV-2 and have shown good efficacy; however, these drugs do not completely inhibit viral shedding episodes and only partially prevent viral transmission.

To understand why HSV-2-directed drugs do not completely eliminate viral shedding, associate in VIDD Dr. Josh Schiffer, VIDD associate member Dr. Amalia Magaret, VIDD member Dr. Anna Wald, and Center President and Director Dr. Larry Corey analyzed pooled data from previously published cohort studies to determine shedding episode frequency and duration, viral production, and viral expansion and decay kinetics between HSV-2-infected persons on antiviral therapy (acyclovir or famcyclovir) and placebo controls. The group analyzed genital swabs that were collected twice daily for 30 days and employed quantitative PCR for viral DNA detection, which is indicative of viral shedding. The authors found that 25% of placebo samples were positive for HSV-2 DNA, while only 5% were positive in persons receiving acyclovir or famcyclovir. Drug treatment also decreased the frequency, expansion rate, duration, and re-expansion likelihood of shedding episodes. However, viral shedding was still detected in those receiving drug treatment. This quantitative analysis helps explain why clinical lesions, asymptomatic viral shedding and transmission still occur despite antiviral drug prophylaxis in infected individuals.

Schiffer JT, Magaret A, Selke S, Corey L, Wald A. Detailed analysis of mucosal herpes simplex virus-2 replication kinetics with and without antiviral therapy. J Antimicrob Chemother 2011 Nov;66(11):2593-600.