Asymptomatic shedding of herpes simplex virus (HSV) is a prominent factor in the transmission of genital herpes. Theoretically, reducing the rate of asymptomatic HSV shedding could reduce virus transmission. Our study [1] showed that suppressive acyclovir had little effect on asymptomatic genital shedding; these findings contrast with those of Wald and colleagues [2]. We reanalyzed our data in the hope that the basis for the conflicting findings could be explained.

Our study involved patients with recurring genital herpes who obtained cultures from themselves and maintained symptom and lesion diaries for a total of more than 6500 days. In this study, asymptomatic shedding was defined by "a positive culture ... not associated with symptoms or lesions on that day or on a preceding or following day" [1]. The intent was to exclude shedding that was associated with episodes of symptoms. By that definition, acyclovir markedly reduced symptomatic shedding but not asymptomatic shedding.

Wald and colleagues [2] defined asymptomatic shedding as a positive culture in the absence of a lesion, regardless of the presence of symptoms. We reexamined our original study using that definition and using a more traditional definition that required a positive culture in the absence of lesions or symptoms on that day alone. The reanalysis confirmed that by either definition, acyclovir inhibited symptomatic viral shedding by 95% to 98% (P < 0.001; Figure 1), confirming the results of Wald and colleagues [2]. Using Wald and coworkers' definition, we found an 82% reduction in asymptomatic shedding (P < 0.001), a rate similar to the 89% to 97% reduction they reported. An intermediate reduction (60%) in asymptomatic shedding was found when events on neighboring calendar days were discounted (P < 0.03).

View larger version (23K): [in this window] [in a new window]   Figure 1. Mean rates of asymptomatic (top) and symptomatic (bottom) genital shedding of herpes simplex virus (HSV), according to the definition of asymptomatic shedding used. The white bars show results for days in which acyclovir was not received; the black bars show the rates when acyclovir was received. Comparisons were made using the Wilcoxon paired-sample test.

Thus, acyclovir can reduce asymptomatic shedding (depending on the clinical definition of this shedding) but cannot entirely prevent it. In the absence of a controlled study, it is premature to presume the effect acyclovir might have on virus transmission because the relative risk associated with each pattern and quantity of viral shedding remains unknown.